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Introduction

Hello and welcome to the KAMP package! This package is designed to calculate the expectation and variance of KAMP (K adjustment by Analytical Moments of the Permutation distribution) for point patterns with marks. The package is partially built on the spatstat package, which is a powerful tool for analyzing spatial data in R. The KAMP package provides functions to simulate point patterns, calculate the KAMP CSR, and visualize the results. The package is designed to be user-friendly and easy to use, with a focus on providing clear and concise output. The package is still in development, and we welcome any feedback or suggestions for improvement. If you have any questions or issues, please feel free to reach out to us.

Setup

library(KAMP)
#library(devtools)
library(tidyverse)
#> ── Attaching core tidyverse packages ──────────────────────── tidyverse 2.0.0 ──
#>  dplyr     1.1.4      readr     2.1.5
#>  forcats   1.0.0      stringr   1.5.1
#>  ggplot2   3.5.2      tibble    3.3.0
#>  lubridate 1.9.4      tidyr     1.3.1
#>  purrr     1.1.0     
#> ── Conflicts ────────────────────────────────────────── tidyverse_conflicts() ──
#>  dplyr::filter() masks stats::filter()
#>  dplyr::lag()    masks stats::lag()
#>  Use the conflicted package (<http://conflicted.r-lib.org/>) to force all conflicts to become errors
library(spatstat.random)
#> Loading required package: spatstat.data
#> Loading required package: spatstat.univar
#> spatstat.univar 3.1-4
#> Loading required package: spatstat.geom
#> spatstat.geom 3.5-0
#> spatstat.random 3.4-1
#devtools::load_all()
set.seed(50)

Ovarian Dataset

The ovarian_df dataset is a small dataframe that contains a snapshot of 5 images of ovarian cancer cells from the HumanOvarianCancerVP() dataset in the VectraPolarisData package. Each image is represented by a unique sample ID, and within each image, there are multiple cells with their respective x and y coordinates. The dataset includes an immune column that indicates whether the cell is an immune cell or a background cell. There is also a phenotype column that indicates the type of immune cell, such as “helper t cells”, “cytotoxic t cells”, “b cells”, or “macrophages”. The x and y columns represent the coordinates of the cells in the image.

data(ovarian_df)
head(ovarian_df)
#>   cell_id                                           sample_id       x       y
#> 1       1 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20592.9 34524.4
#> 2       2 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20859.3 34524.4
#> 3       3 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20591.4 34530.4
#> 4       4 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20744.7 34528.9
#> 5       5 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20419.8 34540.8
#> 6       6 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20741.7 34542.3
#>       immune phenotype
#> 1 background     other
#> 2 background     other
#> 3 background     tumor
#> 4 background     tumor
#> 5 background     other
#> 6 background     tumor

Since we have a dataframe of multiple images, let’s go through, subset our dataframe by id, and plot it.

ids <- unique(ovarian_df$sample_id)
marksvar <- "immune"

for (id in ids) {
  df_sub <- ovarian_df %>% filter(sample_id == id)
  w <- convexhull.xy(df_sub$x, df_sub$y)
  pp_obj <- ppp(df_sub$x, df_sub$y, window = w, marks = df_sub[[marksvar]])

  p <- ggplot(as_tibble(pp_obj), aes(x, y, color = marks)) +
    geom_point(size = 0.6) +
    labs(title = paste("Sample:", id)) +
    theme_minimal()

  print(p)
}

KAMP

Now that we have our data, we can use the kamp() function to calculate the KAMP expectation and variance for both univariate and bivariate data.

Univariate

We can use the kamp() function to calculate the KAMP expectation for univariate data.

The kamp() function has several parameters that allow us to customize the calculation:

  • ppp_obj: The point pattern object created using the ppp() function from the spatstat package.

  • rvals: A sequence of distances at which to calculate the K function.

  • univariate: A logical value indicating whether to calculate the univariate K function (default is TRUE).

  • marksvar1: The name of the marks variable for the first mark (required for univariate).

  • marksvar2: The name of the marks variable for the second mark (optional for univariate).

  • variance: A logical value indicating whether to calculate the variance (default is FALSE).

  • thin: A logical value indicating whether to use thinning (default is FALSE).

  • p_thin: Percentage to thin by (default is 0.5).

For univariate data, we only need to specify one marks variable. In this case, we set univariate = TRUE and variance = FALSE (the default).

  • univariate = TRUE calculates the K function for one mark versus background.

  • variance = FALSE means we only compute the expectation.

  • correction uses translational correction by default.

Subsetting Data

To perform univariate analysis, we can subset our ovarian_df dataframe to include only the first image ID and the immune marks variable.

ids <- unique(ovarian_df$sample_id)
univ_data <- ovarian_df %>% filter(sample_id == ids[1])
marksvar <- "immune"
head(univ_data)
#>   cell_id                                           sample_id       x       y
#> 1       1 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20592.9 34524.4
#> 2       2 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20859.3 34524.4
#> 3       3 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20591.4 34530.4
#> 4       4 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20744.7 34528.9
#> 5       5 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20419.8 34540.8
#> 6       6 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20741.7 34542.3
#>       immune phenotype
#> 1 background     other
#> 2 background     other
#> 3 background     tumor
#> 4 background     tumor
#> 5 background     other
#> 6 background     tumor
w <- convexhull.xy(univ_data$x, univ_data$y)
pp_univ_data <- ppp(univ_data$x, univ_data$y, window = w, marks = univ_data[[marksvar]])

Expectation

We can now calculate the KAMP expectation for the univariate data using the kamp() function. What we are doing here is calculating the KAMP expectation for the immune marks variable against the background cells, using a sequence of distances from 0 to 100 with a step of 10. Furthermore, we use the option univariate = TRUE and specify the marks variable for the first mark as marksvar1 = "immune" - we are not setting marksvar2 since we are only interested in the univariate case.

What’s returned is a data frame with the following columns:

  • r: The distance at which the K function is calculated.

  • k: The K function value.

  • theo_csr: The theoretical CSR (Complete Spatial Randomness) value.

  • kamp_csr: The KAMP CSR value.

  • kamp: The difference between K and the KAMP CSR.

univ_kamp <- kamp(pp_univ_data, 
                  rvals = seq(0, 100, by = 10),
                  univariate = TRUE,
                  marksvar1 = "immune")
#> The point pattern object has more than 10000 points. Switching to border correction

univ_kamp
#> # A tibble: 11 × 5
#>        r      k theo_csr kamp_csr   kamp
#>    <dbl>  <dbl>    <dbl>    <dbl>  <dbl>
#>  1     0     0        0        0      0 
#>  2    10  2338.     314.     521.  1817.
#>  3    20  5855.    1257.    2108.  3747.
#>  4    30 10460.    2827.    4527.  5933.
#>  5    40 14735.    5027.    7727.  7008.
#>  6    50 20228.    7854.   11713.  8515.
#>  7    60 27485.   11310.   16472. 11013.
#>  8    70 35859.   15394.   22039. 13820.
#>  9    80 43814.   20106.   28302. 15511.
#> 10    90 52296.   25447.   35277. 17019.
#> 11   100 60732.   31416.   42914. 17818.

We can visualize KAMP using ggplot2. Plotted here is the original K from translational edge correctionm, the theoretical CSR, and the KAMP CSR. The KAMP CSR is the expected value of K under the null hypothesis of CSR, which is calculated using the analytical moments of the permutation distribution.

univ_kamp %>%
  ggplot(aes(x = r)) +
  geom_line(aes(y = theo_csr, color = "theo_csr", linetype = "theo_csr"), size = 1) +
  geom_line(aes(y = kamp_csr, color = "kamp_csr", linetype = "kamp_csr"), size = 1) +
  geom_line(aes(y = k, color = "k", linetype = "k"), size = 1) +
  geom_hline(yintercept = 0, linetype = "dashed", color = "gray") +
  scale_color_manual(
    values = c(
      "theo_csr" = "black",
      "kamp_csr" = "blue",
      "k" = "red"
    )
  ) +
  scale_linetype_manual(
    values = c(
      "theo_csr" = "solid",
      "kamp_csr" = "solid",
      "k" = "dotted"
    )
  ) +
  labs(
    title = "Univariate KAMP Expectation",
    x = "r",
    y = "Value",
    color = "Series",
    linetype = "Series"
  ) +
  theme_minimal()
#> Warning: Using `size` aesthetic for lines was deprecated in ggplot2 3.4.0.
#>  Please use `linewidth` instead.
#> This warning is displayed once every 8 hours.
#> Call `lifecycle::last_lifecycle_warnings()` to see where this warning was
#> generated.

Looking at the plot, we can see that the KAMP CSR (blue line) is slightly higher than the theoretical CSR (black line) at larger distances. This result aligns with our expectations, as, if we view the plots of the first sample image, the first image is more inhomogenous - i.e. there are large holes/“patches” of empty space that could make the immune cells appear more clustered than expected under CSR.

Let’s plot the differences between k and the theo_csr and kamp_csr to get a better idea:

univ_kamp %>%
  ggplot(aes(x = r)) +
  geom_line(aes(y = k - kamp_csr, color = "k - kamp_csr", linetype = "k - kamp_csr"), size = 1) +
  geom_line(aes(y = k - theo_csr, color = "k - theo_csr", linetype = "k - theo_csr"), size = 1) +
  geom_hline(yintercept = 0, linetype = "dashed", color = "gray") +
  scale_color_manual(
    values = c(
      "k - theo_csr" = "red",
      "k - kamp_csr" = "blue"
    )
  ) +
  scale_linetype_manual(
    values = c(
      "k - theo_csr" = "solid",
      "k - kamp_csr" = "solid"
    )
  ) +
  labs(
    title = "Univariate KAMP Expectation - differences",
    x = "r",
    y = "Value",
    color = "Series",
    linetype = "Series"
  ) +
  theme_minimal()

As expected, the difference between k and the theoretical CSR values tended to be higher than the difference between k and the KAMP CSR values, indicating that the KAMP CSR seems to do a better job accounting for the inhomogenous tissue quality.

Variance

To calculate the variance of the KAMP expectation, we still use the kamp() function, but we set variance = TRUE. This will compute the variance of the KAMP expectation at each distance r. The new output will include all the same columns as before, but with additional column var that contains the variance of the KAMP expectation at each distance, and a p-val column that contains the p-value for the variance test.

Note: variance = TRUE is not compatible with thin = TRUE. If both are set to TRUE, a warning will be thrown and variance will still be calculated, but the results may be unreliable.

univ_kamp_var <- kamp(pp_univ_data,
                       rvals = seq(0, 100, by = 10),
                       univariate = TRUE,
                       marksvar1 = "immune",
                       variance = TRUE)
#> The point pattern object has more than 10000 points. Switching to border correction
#>  ■■■■                               9% |  ETA:  2m
#>  ■■■■■■                            18% |  ETA:  1m
#>  ■■■■■■■■■                         27% |  ETA:  1m
#>  ■■■■■■■■■■■■                      36% |  ETA:  1m
#>  ■■■■■■■■■■■■■■■                   45% |  ETA: 46s
#>  ■■■■■■■■■■■■■■■■■                 55% |  ETA: 38s
#>  ■■■■■■■■■■■■■■■■■■■■              64% |  ETA: 30s
#>  ■■■■■■■■■■■■■■■■■■■■■■■           73% |  ETA: 23s
#>  ■■■■■■■■■■■■■■■■■■■■■■■■■■        82% |  ETA: 15s
#>  ■■■■■■■■■■■■■■■■■■■■■■■■■■■■      91% |  ETA:  8s
univ_kamp_var
#> # A tibble: 11 × 7
#>        r      k theo_csr kamp_csr   kamp      var     pvalue
#>    <dbl>  <dbl>    <dbl>    <dbl>  <dbl>    <dbl>      <dbl>
#>  1     0     0        0        0      0        0  NaN       
#>  2    10  2338.     314.     523.  1816.   18683.   1.43e-40
#>  3    20  5855.    1257.    2108.  3747.   80000.   2.30e-40
#>  4    30 10460.    2827.    4527.  5933.  190355.   2.03e-42
#>  5    40 14735.    5027.    7727.  7008.  367573.   3.34e-31
#>  6    50 20228.    7854.   11713.  8515.  633052.   4.99e-27
#>  7    60 27485.   11310.   16473. 11012. 1019381.   5.33e-28
#>  8    70 35859.   15394.   22040. 13819. 1558782.   8.92e-29
#>  9    80 43814.   20106.   28302. 15511. 2275297.   4.19e-25
#> 10    90 52296.   25447.   35277. 17019. 3211674.   1.09e-21
#> 11   100 60732.   31416.   42914. 17818. 4377696.   8.26e-18

We can visualize the variance of the KAMP expectation using ggplot2:

univ_kamp_var %>%
  ggplot(aes(x = r, y = var)) +
  geom_line() +
  geom_hline(yintercept = 0, linetype = "dashed", color = "blue") +
  labs(title = "Univariate KAMP Variance", x = "r", y = "Variance") +
  theme_minimal()

Bivariate

Subsetting Data

For bivariate analysis, we can subset our ovarian_df dataframe to include two types of immune cells and background cells. In this example, we will use “helper t cells” and “cytotoxic t cells”.

ids <- unique(ovarian_df$sample_id)
biv_data <- ovarian_df %>% 
  filter(sample_id == ids[1]) #%>%
  #filter(phenotype %in% c("helper t cells", "cytotoxic t cells", "other")) %>%
  #droplevels()

marksvar <- "phenotype"

head(biv_data)
#>   cell_id                                           sample_id       x       y
#> 1       1 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20592.9 34524.4
#> 2       2 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20859.3 34524.4
#> 3       3 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20591.4 34530.4
#> 4       4 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20744.7 34528.9
#> 5       5 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20419.8 34540.8
#> 6       6 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20741.7 34542.3
#>       immune phenotype
#> 1 background     other
#> 2 background     other
#> 3 background     tumor
#> 4 background     tumor
#> 5 background     other
#> 6 background     tumor
w <- convexhull.xy(biv_data$x, biv_data$y)
pp_biv_data <- ppp(biv_data$x, biv_data$y, window = w, marks = biv_data[[marksvar]])

Expectation

To calculate the KAMP expectation for bivariate data, we set univariate = FALSE and specify the marks variables for both marks.


marks(pp_biv_data)
#>    [1] other            other            tumor            tumor           
#>    [5] other            tumor            tumor            tumor           
#>    [9] cytotoxic t cell other            other            other           
#>   [13] other            other            tumor            tumor           
#>   [17] other            other            other            tumor           
#>   [21] other            other            tumor            other           
#>   [25] other            other            tumor            tumor           
#>   [29] tumor            other            other            tumor           
#>   [33] tumor            tumor            other            tumor           
#>   [37] other            other            tumor            tumor           
#>   [41] b cell           tumor            other            tumor           
#>   [45] other            other            other            other           
#>   [49] tumor            tumor            other            other           
#>   [53] other            tumor            tumor            tumor           
#>   [57] other            other            other            other           
#>   [61] tumor            tumor            cytotoxic t cell other           
#>   [65] tumor            other            other            other           
#>   [69] tumor            tumor            other            tumor           
#>   [73] tumor            tumor            other            tumor           
#>   [77] other            tumor            other            tumor           
#>   [81] tumor            other            tumor            tumor           
#>   [85] tumor            other            tumor            other           
#>   [89] other            other            other            tumor           
#>   [93] tumor            tumor            tumor            other           
#>   [97] tumor            tumor            other            other           
#>  [101] other            tumor            tumor            other           
#>  [105] other            other            other            tumor           
#>  [109] tumor            tumor            other            other           
#>  [113] other            cytotoxic t cell other            tumor           
#>  [117] other            tumor            tumor            other           
#>  [121] other            other            tumor            other           
#>  [125] tumor            cytotoxic t cell other            cytotoxic t cell
#>  [129] tumor            tumor            other            tumor           
#>  [133] tumor            tumor            other            tumor           
#>  [137] helper t cell    other            tumor            other           
#>  [141] tumor            tumor            tumor            tumor           
#>  [145] tumor            other            other            tumor           
#>  [149] tumor            tumor            tumor            cytotoxic t cell
#>  [153] other            other            other            tumor           
#>  [157] other            tumor            other            other           
#>  [161] other            other            tumor            other           
#>  [165] other            tumor            tumor            other           
#>  [169] cytotoxic t cell other            tumor            tumor           
#>  [173] tumor            tumor            tumor            tumor           
#>  [177] other            cytotoxic t cell tumor            tumor           
#>  [181] tumor            tumor            other            tumor           
#>  [185] other            other            tumor            other           
#>  [189] cytotoxic t cell other            other            other           
#>  [193] tumor            other            tumor            other           
#>  [197] other            other            tumor            other           
#>  [201] other            helper t cell    other            other           
#>  [205] tumor            other            other            other           
#>  [209] other            other            cytotoxic t cell other           
#>  [213] tumor            other            tumor            other           
#>  [217] other            other            other            other           
#>  [221] tumor            other            other            other           
#>  [225] tumor            helper t cell    other            other           
#>  [229] cytotoxic t cell other            other            tumor           
#>  [233] tumor            other            other            other           
#>  [237] other            tumor            tumor            other           
#>  [241] other            tumor            other            tumor           
#>  [245] tumor            tumor            other            other           
#>  [249] other            tumor            other            other           
#>  [253] other            other            other            other           
#>  [257] other            tumor            tumor            other           
#>  [261] other            other            other            other           
#>  [265] tumor            other            other            other           
#>  [269] other            other            tumor            other           
#>  [273] other            other            cytotoxic t cell tumor           
#>  [277] tumor            other            other            other           
#>  [281] other            other            other            other           
#>  [285] other            other            tumor            other           
#>  [289] tumor            other            tumor            other           
#>  [293] helper t cell    other            other            other           
#>  [297] other            tumor            other            other           
#>  [301] other            other            other            other           
#>  [305] other            other            tumor            tumor           
#>  [309] other            other            other            helper t cell   
#>  [313] other            other            other            other           
#>  [317] other            other            other            other           
#>  [321] other            other            other            other           
#>  [325] other            other            other            tumor           
#>  [329] other            other            other            other           
#>  [333] b cell           other            other            other           
#>  [337] other            b cell           other            other           
#>  [341] other            other            other            other           
#>  [345] b cell           other            other            other           
#>  [349] helper t cell    other            other            helper t cell   
#>  [353] cytotoxic t cell other            tumor            other           
#>  [357] other            other            other            cytotoxic t cell
#>  [361] other            other            other            tumor           
#>  [365] other            other            other            tumor           
#>  [369] tumor            other            other            other           
#>  [373] other            tumor            other            other           
#>  [377] other            tumor            tumor            other           
#>  [381] other            other            cytotoxic t cell b cell          
#>  [385] other            tumor            tumor            other           
#>  [389] other            other            other            other           
#>  [393] other            helper t cell    other            other           
#>  [397] tumor            other            other            other           
#>  [401] tumor            other            other            other           
#>  [405] other            tumor            other            other           
#>  [409] tumor            other            tumor            other           
#>  [413] other            other            other            other           
#>  [417] tumor            tumor            cytotoxic t cell helper t cell   
#>  [421] other            other            other            other           
#>  [425] tumor            tumor            tumor            tumor           
#>  [429] tumor            tumor            tumor            tumor           
#>  [433] tumor            tumor            tumor            tumor           
#>  [437] tumor            tumor            tumor            tumor           
#>  [441] tumor            tumor            tumor            tumor           
#>  [445] tumor            tumor            tumor            tumor           
#>  [449] tumor            other            other            tumor           
#>  [453] tumor            tumor            tumor            tumor           
#>  [457] tumor            tumor            tumor            tumor           
#>  [461] tumor            tumor            tumor            tumor           
#>  [465] tumor            tumor            other            other           
#>  [469] tumor            tumor            tumor            tumor           
#>  [473] tumor            tumor            tumor            tumor           
#>  [477] tumor            tumor            tumor            cytotoxic t cell
#>  [481] tumor            tumor            tumor            tumor           
#>  [485] tumor            tumor            tumor            tumor           
#>  [489] cytotoxic t cell tumor            tumor            tumor           
#>  [493] tumor            tumor            tumor            tumor           
#>  [497] tumor            tumor            tumor            tumor           
#>  [501] tumor            tumor            other            tumor           
#>  [505] tumor            tumor            tumor            tumor           
#>  [509] tumor            tumor            tumor            tumor           
#>  [513] tumor            tumor            tumor            tumor           
#>  [517] tumor            tumor            tumor            tumor           
#>  [521] tumor            other            tumor            tumor           
#>  [525] other            tumor            tumor            tumor           
#>  [529] tumor            tumor            tumor            tumor           
#>  [533] tumor            tumor            tumor            tumor           
#>  [537] tumor            tumor            other            other           
#>  [541] tumor            other            tumor            other           
#>  [545] tumor            tumor            other            other           
#>  [549] other            other            other            other           
#>  [553] other            other            other            other           
#>  [557] tumor            other            cytotoxic t cell cytotoxic t cell
#>  [561] tumor            tumor            other            tumor           
#>  [565] other            other            tumor            tumor           
#>  [569] tumor            b cell           tumor            other           
#>  [573] other            tumor            other            other           
#>  [577] other            other            other            other           
#>  [581] other            other            other            tumor           
#>  [585] tumor            tumor            other            other           
#>  [589] other            tumor            other            other           
#>  [593] other            other            other            tumor           
#>  [597] cytotoxic t cell other            other            other           
#>  [601] other            other            other            other           
#>  [605] cytotoxic t cell other            tumor            tumor           
#>  [609] b cell           other            other            tumor           
#>  [613] b cell           other            other            other           
#>  [617] other            tumor            other            tumor           
#>  [621] other            tumor            tumor            other           
#>  [625] other            tumor            tumor            tumor           
#>  [629] other            other            other            cytotoxic t cell
#>  [633] other            tumor            tumor            tumor           
#>  [637] tumor            tumor            tumor            tumor           
#>  [641] tumor            other            other            tumor           
#>  [645] tumor            other            other            tumor           
#>  [649] tumor            tumor            tumor            tumor           
#>  [653] tumor            tumor            tumor            other           
#>  [657] tumor            tumor            tumor            tumor           
#>  [661] tumor            other            tumor            other           
#>  [665] tumor            tumor            tumor            cytotoxic t cell
#>  [669] other            other            tumor            tumor           
#>  [673] tumor            tumor            other            tumor           
#>  [677] other            tumor            tumor            other           
#>  [681] tumor            other            other            other           
#>  [685] other            other            tumor            other           
#>  [689] tumor            tumor            tumor            tumor           
#>  [693] other            other            other            other           
#>  [697] other            other            other            other           
#>  [701] other            tumor            cytotoxic t cell other           
#>  [705] other            tumor            other            other           
#>  [709] other            other            other            other           
#>  [713] other            other            other            other           
#>  [717] other            other            other            other           
#>  [721] other            other            other            tumor           
#>  [725] other            other            other            tumor           
#>  [729] other            other            other            other           
#>  [733] other            tumor            other            tumor           
#>  [737] other            other            tumor            cytotoxic t cell
#>  [741] cytotoxic t cell other            tumor            other           
#>  [745] tumor            tumor            other            other           
#>  [749] tumor            other            other            tumor           
#>  [753] other            tumor            other            tumor           
#>  [757] tumor            other            tumor            tumor           
#>  [761] tumor            tumor            other            tumor           
#>  [765] other            b cell           tumor            tumor           
#>  [769] tumor            tumor            tumor            tumor           
#>  [773] other            other            other            other           
#>  [777] tumor            other            other            tumor           
#>  [781] tumor            tumor            helper t cell    tumor           
#>  [785] tumor            tumor            other            tumor           
#>  [789] other            tumor            other            tumor           
#>  [793] tumor            tumor            tumor            other           
#>  [797] other            tumor            tumor            other           
#>  [801] other            other            tumor            tumor           
#>  [805] tumor            tumor            tumor            tumor           
#>  [809] other            other            other            other           
#>  [813] other            other            tumor            other           
#>  [817] tumor            tumor            tumor            other           
#>  [821] cytotoxic t cell other            other            tumor           
#>  [825] other            other            tumor            tumor           
#>  [829] tumor            other            other            other           
#>  [833] other            other            other            tumor           
#>  [837] other            tumor            tumor            tumor           
#>  [841] other            tumor            other            tumor           
#>  [845] tumor            other            tumor            other           
#>  [849] other            tumor            tumor            other           
#>  [853] tumor            other            tumor            other           
#>  [857] other            other            tumor            tumor           
#>  [861] other            other            other            tumor           
#>  [865] other            tumor            tumor            other           
#>  [869] tumor            other            other            tumor           
#>  [873] tumor            tumor            tumor            tumor           
#>  [877] other            tumor            other            other           
#>  [881] other            other            tumor            other           
#>  [885] other            other            tumor            other           
#>  [889] tumor            tumor            tumor            tumor           
#>  [893] other            tumor            other            other           
#>  [897] tumor            other            tumor            tumor           
#>  [901] other            tumor            other            other           
#>  [905] other            helper t cell    tumor            tumor           
#>  [909] other            other            other            tumor           
#>  [913] other            tumor            tumor            other           
#>  [917] tumor            tumor            tumor            other           
#>  [921] other            other            tumor            other           
#>  [925] tumor            tumor            other            tumor           
#>  [929] other            tumor            tumor            cytotoxic t cell
#>  [933] tumor            other            tumor            tumor           
#>  [937] other            other            other            other           
#>  [941] other            other            tumor            other           
#>  [945] other            other            other            other           
#>  [949] other            tumor            other            tumor           
#>  [953] other            cytotoxic t cell other            tumor           
#>  [957] other            tumor            tumor            other           
#>  [961] other            tumor            other            other           
#>  [965] tumor            other            tumor            tumor           
#>  [969] other            other            tumor            other           
#>  [973] tumor            tumor            other            tumor           
#>  [977] tumor            tumor            other            other           
#>  [981] tumor            other            other            other           
#>  [985] other            tumor            tumor            tumor           
#>  [989] other            tumor            tumor            tumor           
#>  [993] tumor            cytotoxic t cell tumor            tumor           
#>  [997] tumor            other            other            tumor           
#> [1001] other            other            tumor            tumor           
#> [1005] tumor            other            other            tumor           
#> [1009] other            tumor            tumor            other           
#> [1013] other            tumor            other            tumor           
#> [1017] other            tumor            tumor            tumor           
#> [1021] tumor            tumor            tumor            tumor           
#> [1025] tumor            other            tumor            other           
#> [1029] tumor            other            tumor            tumor           
#> [1033] tumor            tumor            other            other           
#> [1037] tumor            other            other            other           
#> [1041] other            tumor            tumor            tumor           
#> [1045] tumor            other            other            other           
#> [1049] tumor            other            tumor            tumor           
#> [1053] tumor            tumor            tumor            other           
#> [1057] other            other            other            other           
#> [1061] other            other            other            tumor           
#> [1065] other            other            other            other           
#> [1069] other            other            tumor            tumor           
#> [1073] other            other            other            tumor           
#> [1077] other            tumor            other            other           
#> [1081] tumor            tumor            tumor            other           
#> [1085] tumor            tumor            tumor            other           
#> [1089] tumor            other            other            tumor           
#> [1093] other            tumor            other            other           
#> [1097] tumor            other            tumor            other           
#> [1101] tumor            other            other            other           
#> [1105] other            other            other            tumor           
#> [1109] tumor            tumor            tumor            other           
#> [1113] tumor            tumor            other            tumor           
#> [1117] other            tumor            cytotoxic t cell tumor           
#> [1121] tumor            tumor            tumor            other           
#> [1125] other            other            tumor            tumor           
#> [1129] tumor            other            other            tumor           
#> [1133] other            other            other            tumor           
#> [1137] tumor            other            other            tumor           
#> [1141] cytotoxic t cell other            other            other           
#> [1145] other            tumor            tumor            other           
#> [1149] tumor            other            other            other           
#> [1153] other            other            other            tumor           
#> [1157] tumor            tumor            other            other           
#> [1161] tumor            tumor            b cell           tumor           
#> [1165] other            tumor            other            other           
#> [1169] other            other            tumor            other           
#> [1173] other            other            other            tumor           
#> [1177] tumor            tumor            tumor            other           
#> [1181] other            tumor            tumor            tumor           
#> [1185] tumor            other            tumor            other           
#> [1189] tumor            other            other            other           
#> [1193] other            other            b cell           tumor           
#> [1197] tumor            other            other            tumor           
#> [1201] other            tumor            tumor            other           
#> [1205] tumor            tumor            other            other           
#> [1209] tumor            other            tumor            other           
#> [1213] tumor            other            other            tumor           
#> [1217] tumor            tumor            other            other           
#> [1221] tumor            other            other            other           
#> [1225] other            other            tumor            tumor           
#> [1229] tumor            tumor            tumor            other           
#> [1233] tumor            tumor            tumor            other           
#> [1237] other            other            other            tumor           
#> [1241] other            tumor            other            tumor           
#> [1245] tumor            other            other            tumor           
#> [1249] tumor            tumor            tumor            tumor           
#> [1253] other            other            tumor            cytotoxic t cell
#> [1257] tumor            tumor            cytotoxic t cell tumor           
#> [1261] other            other            tumor            other           
#> [1265] b cell           tumor            tumor            other           
#> [1269] tumor            tumor            tumor            other           
#> [1273] other            other            tumor            tumor           
#> [1277] other            other            tumor            tumor           
#> [1281] other            other            tumor            other           
#> [1285] tumor            tumor            tumor            other           
#> [1289] other            other            other            other           
#> [1293] other            tumor            other            tumor           
#> [1297] other            tumor            tumor            tumor           
#> [1301] tumor            tumor            other            other           
#> [1305] other            tumor            tumor            tumor           
#> [1309] other            tumor            other            other           
#> [1313] other            tumor            other            tumor           
#> [1317] tumor            tumor            other            other           
#> [1321] tumor            tumor            tumor            tumor           
#> [1325] cytotoxic t cell tumor            other            other           
#> [1329] other            tumor            tumor            other           
#> [1333] tumor            other            tumor            other           
#> [1337] tumor            other            other            tumor           
#> [1341] other            tumor            tumor            other           
#> [1345] tumor            tumor            tumor            other           
#> [1349] tumor            other            tumor            tumor           
#> [1353] other            tumor            tumor            other           
#> [1357] other            other            tumor            other           
#> [1361] tumor            other            other            tumor           
#> [1365] tumor            tumor            tumor            tumor           
#> [1369] tumor            other            other            other           
#> [1373] other            tumor            other            tumor           
#> [1377] other            tumor            tumor            other           
#> [1381] cytotoxic t cell other            tumor            other           
#> [1385] tumor            tumor            other            tumor           
#> [1389] tumor            tumor            tumor            tumor           
#> [1393] tumor            tumor            tumor            other           
#> [1397] other            other            other            other           
#> [1401] tumor            tumor            tumor            other           
#> [1405] other            other            other            other           
#> [1409] other            tumor            tumor            other           
#> [1413] tumor            cytotoxic t cell other            tumor           
#> [1417] tumor            tumor            other            tumor           
#> [1421] other            tumor            cytotoxic t cell tumor           
#> [1425] other            other            tumor            tumor           
#> [1429] tumor            tumor            other            tumor           
#> [1433] tumor            other            tumor            other           
#> [1437] other            tumor            tumor            tumor           
#> [1441] tumor            tumor            other            tumor           
#> [1445] tumor            tumor            other            tumor           
#> [1449] tumor            tumor            tumor            other           
#> [1453] tumor            tumor            tumor            tumor           
#> [1457] other            tumor            other            tumor           
#> [1461] tumor            cytotoxic t cell other            tumor           
#> [1465] tumor            other            tumor            tumor           
#> [1469] tumor            tumor            other            other           
#> [1473] tumor            tumor            tumor            tumor           
#> [1477] tumor            other            tumor            other           
#> [1481] other            tumor            tumor            tumor           
#> [1485] tumor            other            tumor            tumor           
#> [1489] tumor            tumor            tumor            tumor           
#> [1493] tumor            other            other            cytotoxic t cell
#> [1497] other            tumor            other            helper t cell   
#> [1501] other            tumor            tumor            tumor           
#> [1505] other            other            other            tumor           
#> [1509] tumor            other            tumor            other           
#> [1513] other            cytotoxic t cell tumor            tumor           
#> [1517] tumor            tumor            tumor            other           
#> [1521] other            tumor            tumor            tumor           
#> [1525] tumor            other            tumor            other           
#> [1529] tumor            tumor            tumor            tumor           
#> [1533] tumor            other            tumor            tumor           
#> [1537] tumor            tumor            tumor            tumor           
#> [1541] tumor            tumor            other            other           
#> [1545] tumor            tumor            tumor            tumor           
#> [1549] tumor            b cell           cytotoxic t cell tumor           
#> [1553] cytotoxic t cell helper t cell    tumor            other           
#> [1557] tumor            tumor            other            tumor           
#> [1561] tumor            other            tumor            tumor           
#> [1565] other            tumor            tumor            tumor           
#> [1569] other            tumor            other            tumor           
#> [1573] other            other            tumor            tumor           
#> [1577] tumor            tumor            tumor            tumor           
#> [1581] tumor            other            other            tumor           
#> [1585] tumor            tumor            tumor            other           
#> [1589] tumor            other            tumor            other           
#> [1593] other            other            tumor            cytotoxic t cell
#> [1597] other            tumor            other            cytotoxic t cell
#> [1601] other            other            other            other           
#> [1605] tumor            tumor            cytotoxic t cell tumor           
#> [1609] other            tumor            tumor            other           
#> [1613] other            other            tumor            tumor           
#> [1617] other            other            other            tumor           
#> [1621] other            tumor            tumor            tumor           
#> [1625] other            other            tumor            other           
#> [1629] other            tumor            other            tumor           
#> [1633] tumor            other            other            tumor           
#> [1637] other            tumor            tumor            other           
#> [1641] other            tumor            cytotoxic t cell tumor           
#> [1645] other            other            other            tumor           
#> [1649] tumor            other            tumor            tumor           
#> [1653] tumor            tumor            tumor            other           
#> [1657] tumor            other            tumor            other           
#> [1661] tumor            tumor            other            other           
#> [1665] other            tumor            tumor            tumor           
#> [1669] tumor            tumor            other            tumor           
#> [1673] tumor            tumor            tumor            tumor           
#> [1677] tumor            other            tumor            tumor           
#> [1681] tumor            tumor            other            tumor           
#> [1685] tumor            helper t cell    cytotoxic t cell tumor           
#> [1689] tumor            tumor            tumor            other           
#> [1693] cytotoxic t cell other            tumor            other           
#> [1697] tumor            tumor            tumor            tumor           
#> [1701] tumor            cytotoxic t cell tumor            cytotoxic t cell
#> [1705] tumor            tumor            tumor            tumor           
#> [1709] tumor            other            tumor            tumor           
#> [1713] other            other            tumor            tumor           
#> [1717] tumor            tumor            other            tumor           
#> [1721] tumor            tumor            tumor            tumor           
#> [1725] tumor            other            other            tumor           
#> [1729] tumor            other            tumor            other           
#> [1733] tumor            tumor            tumor            tumor           
#> [1737] tumor            tumor            tumor            tumor           
#> [1741] other            other            tumor            tumor           
#> [1745] tumor            other            tumor            tumor           
#> [1749] tumor            tumor            tumor            tumor           
#> [1753] tumor            other            tumor            b cell          
#> [1757] tumor            tumor            tumor            other           
#> [1761] other            other            tumor            tumor           
#> [1765] tumor            cytotoxic t cell tumor            other           
#> [1769] tumor            tumor            tumor            other           
#> [1773] tumor            tumor            tumor            tumor           
#> [1777] tumor            other            tumor            tumor           
#> [1781] other            tumor            tumor            tumor           
#> [1785] tumor            helper t cell    tumor            tumor           
#> [1789] other            tumor            tumor            tumor           
#> [1793] other            tumor            tumor            tumor           
#> [1797] other            cytotoxic t cell tumor            b cell          
#> [1801] other            tumor            tumor            other           
#> [1805] tumor            tumor            tumor            tumor           
#> [1809] tumor            tumor            other            other           
#> [1813] other            tumor            other            tumor           
#> [1817] other            tumor            tumor            other           
#> [1821] tumor            other            tumor            tumor           
#> [1825] other            tumor            tumor            tumor           
#> [1829] tumor            tumor            other            other           
#> [1833] tumor            tumor            tumor            other           
#> [1837] other            tumor            tumor            tumor           
#> [1841] other            tumor            tumor            tumor           
#> [1845] tumor            tumor            tumor            tumor           
#> [1849] tumor            other            tumor            other           
#> [1853] tumor            tumor            tumor            tumor           
#> [1857] tumor            tumor            tumor            other           
#> [1861] other            cytotoxic t cell tumor            tumor           
#> [1865] other            tumor            tumor            tumor           
#> [1869] other            other            other            tumor           
#> [1873] tumor            tumor            other            other           
#> [1877] tumor            other            other            other           
#> [1881] tumor            tumor            tumor            other           
#> [1885] tumor            tumor            tumor            tumor           
#> [1889] cytotoxic t cell tumor            tumor            other           
#> [1893] other            tumor            other            tumor           
#> [1897] tumor            tumor            other            other           
#> [1901] other            tumor            tumor            tumor           
#> [1905] tumor            tumor            other            cytotoxic t cell
#> [1909] other            tumor            tumor            tumor           
#> [1913] tumor            tumor            tumor            tumor           
#> [1917] tumor            tumor            other            other           
#> [1921] cytotoxic t cell tumor            tumor            tumor           
#> [1925] tumor            tumor            other            tumor           
#> [1929] tumor            tumor            tumor            tumor           
#> [1933] tumor            tumor            other            tumor           
#> [1937] other            tumor            cytotoxic t cell tumor           
#> [1941] tumor            other            other            tumor           
#> [1945] other            tumor            b cell           tumor           
#> [1949] tumor            tumor            tumor            other           
#> [1953] other            tumor            other            tumor           
#> [1957] other            tumor            tumor            tumor           
#> [1961] tumor            tumor            tumor            other           
#> [1965] tumor            tumor            tumor            tumor           
#> [1969] tumor            tumor            tumor            other           
#> [1973] tumor            tumor            other            other           
#> [1977] tumor            other            tumor            other           
#> [1981] other            tumor            other            other           
#> [1985] other            tumor            tumor            other           
#> [1989] other            other            tumor            tumor           
#> [1993] tumor            tumor            other            cytotoxic t cell
#> [1997] tumor            tumor            tumor            tumor           
#> [2001] other            other            tumor            b cell          
#> [2005] other            tumor            tumor            other           
#> [2009] tumor            tumor            other            other           
#> [2013] other            tumor            tumor            other           
#> [2017] tumor            tumor            tumor            tumor           
#> [2021] other            other            tumor            tumor           
#> [2025] tumor            tumor            tumor            other           
#> [2029] other            tumor            tumor            other           
#> [2033] tumor            other            tumor            tumor           
#> [2037] tumor            tumor            other            tumor           
#> [2041] tumor            tumor            tumor            tumor           
#> [2045] tumor            other            tumor            tumor           
#> [2049] tumor            tumor            tumor            tumor           
#> [2053] other            tumor            tumor            tumor           
#> [2057] tumor            tumor            tumor            tumor           
#> [2061] tumor            tumor            other            other           
#> [2065] other            tumor            tumor            other           
#> [2069] tumor            other            tumor            other           
#> [2073] tumor            other            tumor            b cell          
#> [2077] tumor            other            tumor            other           
#> [2081] other            tumor            tumor            tumor           
#> [2085] tumor            tumor            tumor            tumor           
#> [2089] tumor            tumor            tumor            tumor           
#> [2093] tumor            tumor            tumor            tumor           
#> [2097] other            tumor            tumor            tumor           
#> [2101] other            tumor            tumor            tumor           
#> [2105] tumor            other            tumor            other           
#> [2109] tumor            tumor            tumor            tumor           
#> [2113] tumor            tumor            other            tumor           
#> [2117] tumor            tumor            tumor            other           
#> [2121] tumor            tumor            other            b cell          
#> [2125] tumor            other            tumor            tumor           
#> [2129] tumor            tumor            other            other           
#> [2133] other            tumor            other            tumor           
#> [2137] tumor            tumor            tumor            tumor           
#> [2141] other            other            tumor            tumor           
#> [2145] tumor            tumor            other            tumor           
#> [2149] tumor            tumor            other            tumor           
#> [2153] tumor            other            tumor            tumor           
#> [2157] cytotoxic t cell other            other            tumor           
#> [2161] other            tumor            tumor            tumor           
#> [2165] tumor            tumor            tumor            tumor           
#> [2169] tumor            other            b cell           other           
#> [2173] other            other            tumor            other           
#> [2177] tumor            tumor            other            other           
#> [2181] tumor            tumor            tumor            tumor           
#> [2185] tumor            tumor            tumor            tumor           
#> [2189] tumor            tumor            tumor            other           
#> [2193] tumor            tumor            tumor            other           
#> [2197] tumor            tumor            tumor            tumor           
#> [2201] b cell           tumor            other            tumor           
#> [2205] tumor            tumor            tumor            other           
#> [2209] other            tumor            tumor            tumor           
#> [2213] other            other            tumor            other           
#> [2217] tumor            tumor            tumor            other           
#> [2221] tumor            tumor            other            tumor           
#> [2225] other            tumor            other            other           
#> [2229] tumor            tumor            other            tumor           
#> [2233] tumor            tumor            tumor            tumor           
#> [2237] other            other            tumor            tumor           
#> [2241] tumor            tumor            tumor            tumor           
#> [2245] other            other            tumor            other           
#> [2249] tumor            tumor            tumor            other           
#> [2253] tumor            other            other            tumor           
#> [2257] tumor            tumor            tumor            tumor           
#> [2261] tumor            other            tumor            tumor           
#> [2265] tumor            tumor            tumor            tumor           
#> [2269] tumor            other            tumor            tumor           
#> [2273] tumor            other            tumor            other           
#> [2277] tumor            tumor            other            tumor           
#> [2281] other            tumor            tumor            tumor           
#> [2285] tumor            tumor            helper t cell    tumor           
#> [2289] tumor            tumor            tumor            tumor           
#> [2293] tumor            other            tumor            tumor           
#> [2297] other            other            tumor            tumor           
#> [2301] other            tumor            tumor            tumor           
#> [2305] other            tumor            tumor            tumor           
#> [2309] tumor            tumor            tumor            cytotoxic t cell
#> [2313] other            tumor            tumor            other           
#> [2317] tumor            tumor            other            tumor           
#> [2321] tumor            other            tumor            other           
#> [2325] tumor            other            b cell           other           
#> [2329] tumor            other            cytotoxic t cell tumor           
#> [2333] tumor            tumor            tumor            tumor           
#> [2337] tumor            other            tumor            tumor           
#> [2341] other            tumor            other            other           
#> [2345] other            other            tumor            tumor           
#> [2349] tumor            tumor            tumor            tumor           
#> [2353] tumor            tumor            tumor            other           
#> [2357] other            tumor            other            other           
#> [2361] tumor            other            tumor            b cell          
#> [2365] tumor            tumor            tumor            tumor           
#> [2369] tumor            tumor            other            tumor           
#> [2373] tumor            other            other            tumor           
#> [2377] cytotoxic t cell other            other            other           
#> [2381] tumor            tumor            other            helper t cell   
#> [2385] tumor            tumor            tumor            other           
#> [2389] tumor            tumor            other            tumor           
#> [2393] tumor            other            cytotoxic t cell cytotoxic t cell
#> [2397] tumor            other            tumor            tumor           
#> [2401] other            b cell           tumor            tumor           
#> [2405] other            other            tumor            tumor           
#> [2409] other            other            tumor            tumor           
#> [2413] other            other            tumor            tumor           
#> [2417] tumor            tumor            b cell           tumor           
#> [2421] tumor            tumor            other            tumor           
#> [2425] tumor            b cell           tumor            other           
#> [2429] tumor            other            tumor            tumor           
#> [2433] tumor            other            tumor            tumor           
#> [2437] tumor            cytotoxic t cell tumor            tumor           
#> [2441] tumor            other            other            other           
#> [2445] tumor            tumor            tumor            other           
#> [2449] other            tumor            tumor            cytotoxic t cell
#> [2453] cytotoxic t cell tumor            tumor            other           
#> [2457] tumor            tumor            tumor            tumor           
#> [2461] tumor            tumor            tumor            tumor           
#> [2465] tumor            tumor            tumor            tumor           
#> [2469] tumor            tumor            tumor            other           
#> [2473] tumor            tumor            tumor            tumor           
#> [2477] tumor            tumor            tumor            other           
#> [2481] tumor            other            tumor            tumor           
#> [2485] tumor            tumor            tumor            tumor           
#> [2489] tumor            tumor            tumor            tumor           
#> [2493] tumor            tumor            tumor            tumor           
#> [2497] tumor            tumor            tumor            tumor           
#> [2501] other            tumor            other            tumor           
#> [2505] tumor            tumor            tumor            tumor           
#> [2509] tumor            cytotoxic t cell tumor            other           
#> [2513] tumor            tumor            tumor            tumor           
#> [2517] tumor            tumor            tumor            tumor           
#> [2521] tumor            tumor            tumor            other           
#> [2525] tumor            tumor            tumor            tumor           
#> [2529] cytotoxic t cell other            tumor            other           
#> [2533] tumor            tumor            tumor            tumor           
#> [2537] tumor            b cell           tumor            tumor           
#> [2541] tumor            tumor            tumor            tumor           
#> [2545] tumor            cytotoxic t cell other            other           
#> [2549] other            helper t cell    b cell           tumor           
#> [2553] tumor            tumor            tumor            tumor           
#> [2557] tumor            cytotoxic t cell tumor            tumor           
#> [2561] tumor            tumor            other            other           
#> [2565] other            cytotoxic t cell other            cytotoxic t cell
#> [2569] tumor            tumor            tumor            tumor           
#> [2573] tumor            tumor            other            tumor           
#> [2577] tumor            tumor            tumor            cytotoxic t cell
#> [2581] tumor            tumor            other            other           
#> [2585] tumor            tumor            other            tumor           
#> [2589] other            cytotoxic t cell tumor            tumor           
#> [2593] other            other            tumor            other           
#> [2597] tumor            other            other            tumor           
#> [2601] other            tumor            other            tumor           
#> [2605] tumor            tumor            other            tumor           
#> [2609] tumor            other            other            tumor           
#> [2613] tumor            tumor            other            tumor           
#> [2617] tumor            tumor            tumor            tumor           
#> [2621] tumor            tumor            helper t cell    other           
#> [2625] tumor            other            tumor            other           
#> [2629] other            cytotoxic t cell other            tumor           
#> [2633] other            other            tumor            other           
#> [2637] other            other            tumor            other           
#> [2641] tumor            tumor            tumor            tumor           
#> [2645] tumor            tumor            other            tumor           
#> [2649] other            other            tumor            tumor           
#> [2653] other            tumor            tumor            other           
#> [2657] other            other            tumor            tumor           
#> [2661] tumor            cytotoxic t cell tumor            tumor           
#> [2665] other            tumor            tumor            tumor           
#> [2669] tumor            tumor            tumor            tumor           
#> [2673] tumor            other            tumor            tumor           
#> [2677] cytotoxic t cell tumor            other            tumor           
#> [2681] tumor            cytotoxic t cell tumor            tumor           
#> [2685] tumor            other            tumor            tumor           
#> [2689] other            tumor            tumor            tumor           
#> [2693] cytotoxic t cell cytotoxic t cell tumor            tumor           
#> [2697] other            cytotoxic t cell cytotoxic t cell other           
#> [2701] tumor            other            tumor            tumor           
#> [2705] tumor            tumor            other            tumor           
#> [2709] tumor            cytotoxic t cell tumor            tumor           
#> [2713] tumor            other            cytotoxic t cell tumor           
#> [2717] tumor            tumor            tumor            tumor           
#> [2721] other            tumor            other            tumor           
#> [2725] tumor            other            tumor            tumor           
#> [2729] cytotoxic t cell other            tumor            tumor           
#> [2733] other            tumor            tumor            tumor           
#> [2737] other            tumor            other            other           
#> [2741] tumor            tumor            tumor            other           
#> [2745] tumor            tumor            tumor            tumor           
#> [2749] cytotoxic t cell other            tumor            other           
#> [2753] tumor            tumor            tumor            tumor           
#> [2757] tumor            cytotoxic t cell tumor            tumor           
#> [2761] other            tumor            other            tumor           
#> [2765] cytotoxic t cell tumor            other            other           
#> [2769] tumor            tumor            other            tumor           
#> [2773] tumor            tumor            b cell           other           
#> [2777] other            tumor            tumor            tumor           
#> [2781] tumor            tumor            other            tumor           
#> [2785] tumor            other            tumor            tumor           
#> [2789] tumor            tumor            tumor            cytotoxic t cell
#> [2793] tumor            tumor            tumor            tumor           
#> [2797] tumor            tumor            other            tumor           
#> [2801] tumor            tumor            other            tumor           
#> [2805] tumor            tumor            tumor            tumor           
#> [2809] tumor            tumor            tumor            tumor           
#> [2813] other            tumor            other            tumor           
#> [2817] tumor            other            tumor            tumor           
#> [2821] tumor            tumor            other            tumor           
#> [2825] tumor            tumor            other            tumor           
#> [2829] tumor            tumor            tumor            other           
#> [2833] tumor            tumor            tumor            other           
#> [2837] other            other            tumor            tumor           
#> [2841] other            tumor            other            tumor           
#> [2845] tumor            tumor            other            other           
#> [2849] tumor            tumor            tumor            other           
#> [2853] tumor            tumor            tumor            tumor           
#> [2857] tumor            tumor            tumor            tumor           
#> [2861] tumor            tumor            other            other           
#> [2865] other            other            other            tumor           
#> [2869] tumor            tumor            tumor            tumor           
#> [2873] other            tumor            other            tumor           
#> [2877] tumor            tumor            other            tumor           
#> [2881] tumor            other            tumor            tumor           
#> [2885] tumor            other            tumor            tumor           
#> [2889] other            tumor            tumor            tumor           
#> [2893] tumor            tumor            other            tumor           
#> [2897] tumor            tumor            other            tumor           
#> [2901] tumor            tumor            other            other           
#> [2905] tumor            tumor            tumor            tumor           
#> [2909] tumor            other            other            tumor           
#> [2913] tumor            tumor            other            tumor           
#> [2917] tumor            tumor            tumor            tumor           
#> [2921] cytotoxic t cell other            helper t cell    other           
#> [2925] tumor            tumor            other            tumor           
#> [2929] tumor            other            tumor            tumor           
#> [2933] tumor            other            other            tumor           
#> [2937] tumor            tumor            tumor            tumor           
#> [2941] tumor            other            tumor            tumor           
#> [2945] tumor            tumor            tumor            tumor           
#> [2949] tumor            other            tumor            other           
#> [2953] tumor            tumor            tumor            other           
#> [2957] tumor            tumor            tumor            tumor           
#> [2961] tumor            tumor            tumor            other           
#> [2965] other            tumor            other            tumor           
#> [2969] other            other            tumor            tumor           
#> [2973] tumor            tumor            tumor            tumor           
#> [2977] other            tumor            other            tumor           
#> [2981] other            cytotoxic t cell b cell           other           
#> [2985] other            tumor            tumor            tumor           
#> [2989] tumor            tumor            tumor            tumor           
#> [2993] other            other            other            tumor           
#> [2997] other            other            other            other           
#> [3001] tumor            other            tumor            tumor           
#> [3005] tumor            tumor            tumor            tumor           
#> [3009] other            other            tumor            tumor           
#> [3013] tumor            tumor            tumor            other           
#> [3017] tumor            tumor            tumor            other           
#> [3021] tumor            tumor            other            tumor           
#> [3025] tumor            tumor            other            b cell          
#> [3029] other            other            tumor            tumor           
#> [3033] other            other            tumor            tumor           
#> [3037] tumor            other            other            tumor           
#> [3041] tumor            other            other            other           
#> [3045] tumor            tumor            tumor            tumor           
#> [3049] tumor            other            tumor            tumor           
#> [3053] tumor            tumor            tumor            tumor           
#> [3057] tumor            tumor            tumor            other           
#> [3061] tumor            tumor            tumor            other           
#> [3065] tumor            tumor            tumor            tumor           
#> [3069] tumor            tumor            other            tumor           
#> [3073] tumor            other            cytotoxic t cell tumor           
#> [3077] tumor            tumor            tumor            other           
#> [3081] other            tumor            tumor            other           
#> [3085] tumor            tumor            tumor            tumor           
#> [3089] tumor            other            tumor            other           
#> [3093] tumor            other            tumor            other           
#> [3097] tumor            other            tumor            other           
#> [3101] tumor            other            cytotoxic t cell tumor           
#> [3105] tumor            tumor            tumor            tumor           
#> [3109] tumor            tumor            tumor            tumor           
#> [3113] tumor            other            b cell           tumor           
#> [3117] tumor            tumor            tumor            tumor           
#> [3121] other            other            other            other           
#> [3125] tumor            tumor            tumor            tumor           
#> [3129] tumor            tumor            b cell           tumor           
#> [3133] tumor            tumor            tumor            tumor           
#> [3137] tumor            tumor            tumor            tumor           
#> [3141] tumor            tumor            other            tumor           
#> [3145] tumor            other            tumor            tumor           
#> [3149] tumor            tumor            other            tumor           
#> [3153] tumor            b cell           tumor            tumor           
#> [3157] tumor            other            cytotoxic t cell tumor           
#> [3161] tumor            tumor            other            cytotoxic t cell
#> [3165] other            tumor            tumor            cytotoxic t cell
#> [3169] tumor            other            tumor            other           
#> [3173] tumor            tumor            other            tumor           
#> [3177] tumor            tumor            cytotoxic t cell tumor           
#> [3181] tumor            tumor            other            cytotoxic t cell
#> [3185] tumor            other            other            tumor           
#> [3189] other            tumor            tumor            other           
#> [3193] other            other            tumor            tumor           
#> [3197] tumor            tumor            tumor            other           
#> [3201] cytotoxic t cell tumor            tumor            other           
#> [3205] other            tumor            tumor            tumor           
#> [3209] other            tumor            other            tumor           
#> [3213] tumor            tumor            tumor            tumor           
#> [3217] tumor            tumor            tumor            other           
#> [3221] other            tumor            other            tumor           
#> [3225] tumor            tumor            other            other           
#> [3229] tumor            tumor            tumor            other           
#> [3233] tumor            tumor            tumor            tumor           
#> [3237] other            tumor            other            tumor           
#> [3241] tumor            tumor            tumor            tumor           
#> [3245] tumor            other            tumor            tumor           
#> [3249] tumor            other            tumor            other           
#> [3253] other            tumor            tumor            tumor           
#> [3257] other            other            tumor            other           
#> [3261] tumor            other            tumor            other           
#> [3265] other            tumor            tumor            other           
#> [3269] tumor            tumor            other            tumor           
#> [3273] tumor            tumor            other            tumor           
#> [3277] tumor            other            tumor            tumor           
#> [3281] tumor            tumor            other            tumor           
#> [3285] other            tumor            other            cytotoxic t cell
#> [3289] tumor            tumor            tumor            tumor           
#> [3293] other            other            tumor            tumor           
#> [3297] tumor            tumor            tumor            other           
#> [3301] tumor            other            other            tumor           
#> [3305] tumor            tumor            other            tumor           
#> [3309] other            other            cytotoxic t cell other           
#> [3313] other            tumor            tumor            tumor           
#> [3317] tumor            tumor            other            tumor           
#> [3321] cytotoxic t cell tumor            other            tumor           
#> [3325] tumor            tumor            other            other           
#> [3329] tumor            tumor            tumor            tumor           
#> [3333] tumor            tumor            tumor            tumor           
#> [3337] other            other            other            tumor           
#> [3341] other            other            tumor            other           
#> [3345] other            tumor            other            tumor           
#> [3349] tumor            tumor            tumor            tumor           
#> [3353] other            tumor            other            other           
#> [3357] tumor            tumor            tumor            other           
#> [3361] other            cytotoxic t cell tumor            tumor           
#> [3365] tumor            tumor            tumor            tumor           
#> [3369] tumor            other            other            tumor           
#> [3373] other            tumor            tumor            tumor           
#> [3377] tumor            tumor            other            tumor           
#> [3381] tumor            tumor            tumor            tumor           
#> [3385] tumor            tumor            tumor            tumor           
#> [3389] tumor            tumor            tumor            tumor           
#> [3393] other            tumor            tumor            tumor           
#> [3397] tumor            tumor            tumor            other           
#> [3401] tumor            tumor            tumor            tumor           
#> [3405] tumor            tumor            tumor            tumor           
#> [3409] other            tumor            tumor            tumor           
#> [3413] tumor            tumor            tumor            tumor           
#> [3417] other            tumor            tumor            cytotoxic t cell
#> [3421] tumor            other            tumor            tumor           
#> [3425] tumor            tumor            other            tumor           
#> [3429] other            other            tumor            tumor           
#> [3433] tumor            tumor            other            tumor           
#> [3437] tumor            cytotoxic t cell other            other           
#> [3441] tumor            tumor            other            tumor           
#> [3445] other            other            tumor            tumor           
#> [3449] tumor            tumor            tumor            tumor           
#> [3453] other            tumor            tumor            other           
#> [3457] tumor            tumor            tumor            other           
#> [3461] other            tumor            tumor            tumor           
#> [3465] tumor            tumor            other            tumor           
#> [3469] tumor            tumor            other            tumor           
#> [3473] tumor            tumor            tumor            tumor           
#> [3477] tumor            tumor            tumor            tumor           
#> [3481] other            other            tumor            other           
#> [3485] other            other            cytotoxic t cell tumor           
#> [3489] tumor            tumor            other            other           
#> [3493] other            tumor            other            tumor           
#> [3497] tumor            tumor            tumor            other           
#> [3501] other            tumor            tumor            other           
#> [3505] other            tumor            tumor            tumor           
#> [3509] tumor            other            other            tumor           
#> [3513] tumor            tumor            tumor            other           
#> [3517] tumor            tumor            tumor            tumor           
#> [3521] tumor            tumor            tumor            tumor           
#> [3525] other            tumor            tumor            other           
#> [3529] other            tumor            other            tumor           
#> [3533] tumor            other            tumor            tumor           
#> [3537] tumor            tumor            cytotoxic t cell other           
#> [3541] other            other            tumor            tumor           
#> [3545] tumor            tumor            other            tumor           
#> [3549] tumor            tumor            tumor            tumor           
#> [3553] other            cytotoxic t cell other            other           
#> [3557] other            tumor            tumor            tumor           
#> [3561] tumor            other            tumor            other           
#> [3565] tumor            other            cytotoxic t cell other           
#> [3569] tumor            cytotoxic t cell other            other           
#> [3573] tumor            tumor            other            other           
#> [3577] tumor            tumor            tumor            tumor           
#> [3581] tumor            tumor            tumor            tumor           
#> [3585] other            tumor            other            tumor           
#> [3589] other            tumor            tumor            tumor           
#> [3593] tumor            tumor            tumor            tumor           
#> [3597] tumor            other            tumor            tumor           
#> [3601] tumor            tumor            other            other           
#> [3605] tumor            other            other            other           
#> [3609] tumor            tumor            tumor            other           
#> [3613] other            tumor            tumor            tumor           
#> [3617] tumor            tumor            tumor            other           
#> [3621] tumor            other            tumor            tumor           
#> [3625] tumor            tumor            tumor            tumor           
#> [3629] other            tumor            other            tumor           
#> [3633] cytotoxic t cell b cell           other            cytotoxic t cell
#> [3637] tumor            tumor            tumor            tumor           
#> [3641] other            other            tumor            tumor           
#> [3645] tumor            tumor            tumor            tumor           
#> [3649] other            other            other            tumor           
#> [3653] tumor            other            tumor            tumor           
#> [3657] tumor            tumor            tumor            b cell          
#> [3661] other            other            tumor            tumor           
#> [3665] other            tumor            tumor            tumor           
#> [3669] other            other            tumor            tumor           
#> [3673] other            tumor            tumor            other           
#> [3677] b cell           tumor            tumor            other           
#> [3681] tumor            other            other            tumor           
#> [3685] tumor            other            tumor            tumor           
#> [3689] tumor            tumor            other            tumor           
#> [3693] tumor            tumor            other            other           
#> [3697] other            other            other            tumor           
#> [3701] other            other            cytotoxic t cell other           
#> [3705] cytotoxic t cell other            tumor            tumor           
#> [3709] other            other            tumor            tumor           
#> [3713] other            other            other            tumor           
#> [3717] tumor            cytotoxic t cell tumor            tumor           
#> [3721] tumor            other            other            tumor           
#> [3725] tumor            other            tumor            other           
#> [3729] other            tumor            other            other           
#> [3733] tumor            other            tumor            other           
#> [3737] tumor            tumor            tumor            other           
#> [3741] tumor            other            tumor            tumor           
#> [3745] other            other            tumor            tumor           
#> [3749] tumor            other            other            tumor           
#> [3753] tumor            other            other            other           
#> [3757] other            tumor            tumor            other           
#> [3761] other            tumor            tumor            tumor           
#> [3765] other            other            cytotoxic t cell b cell          
#> [3769] cytotoxic t cell tumor            other            other           
#> [3773] cytotoxic t cell other            other            tumor           
#> [3777] tumor            tumor            tumor            other           
#> [3781] tumor            tumor            other            tumor           
#> [3785] tumor            tumor            tumor            other           
#> [3789] other            other            other            tumor           
#> [3793] tumor            other            tumor            tumor           
#> [3797] other            other            tumor            tumor           
#> [3801] tumor            other            other            tumor           
#> [3805] other            tumor            tumor            other           
#> [3809] other            tumor            tumor            tumor           
#> [3813] tumor            tumor            tumor            other           
#> [3817] other            other            other            cytotoxic t cell
#> [3821] other            tumor            cytotoxic t cell other           
#> [3825] other            cytotoxic t cell other            tumor           
#> [3829] other            other            other            other           
#> [3833] other            tumor            other            tumor           
#> [3837] other            tumor            tumor            other           
#> [3841] tumor            tumor            other            tumor           
#> [3845] other            tumor            other            tumor           
#> [3849] other            tumor            other            other           
#> [3853] tumor            tumor            tumor            tumor           
#> [3857] other            tumor            tumor            other           
#> [3861] tumor            tumor            other            tumor           
#> [3865] other            other            other            tumor           
#> [3869] tumor            other            tumor            tumor           
#> [3873] tumor            tumor            other            other           
#> [3877] tumor            other            other            other           
#> [3881] other            tumor            other            other           
#> [3885] tumor            tumor            tumor            other           
#> [3889] tumor            other            other            tumor           
#> [3893] tumor            tumor            other            other           
#> [3897] other            other            tumor            other           
#> [3901] other            tumor            tumor            other           
#> [3905] other            other            tumor            other           
#> [3909] tumor            tumor            other            tumor           
#> [3913] tumor            tumor            other            other           
#> [3917] tumor            tumor            other            other           
#> [3921] other            other            other            other           
#> [3925] tumor            other            other            tumor           
#> [3929] tumor            tumor            tumor            tumor           
#> [3933] other            other            tumor            tumor           
#> [3937] b cell           other            tumor            tumor           
#> [3941] b cell           tumor            other            other           
#> [3945] tumor            tumor            other            tumor           
#> [3949] other            tumor            tumor            tumor           
#> [3953] tumor            tumor            other            other           
#> [3957] other            tumor            tumor            other           
#> [3961] other            cytotoxic t cell tumor            other           
#> [3965] other            tumor            other            tumor           
#> [3969] tumor            tumor            other            tumor           
#> [3973] tumor            other            tumor            tumor           
#> [3977] other            tumor            tumor            b cell          
#> [3981] other            other            tumor            tumor           
#> [3985] other            other            tumor            other           
#> [3989] other            other            tumor            tumor           
#> [3993] tumor            tumor            tumor            other           
#> [3997] tumor            tumor            tumor            tumor           
#> [4001] other            tumor            tumor            other           
#> [4005] other            other            tumor            tumor           
#> [4009] tumor            tumor            tumor            tumor           
#> [4013] tumor            tumor            other            other           
#> [4017] other            other            other            other           
#> [4021] tumor            other            other            tumor           
#> [4025] tumor            other            other            cytotoxic t cell
#> [4029] other            other            tumor            tumor           
#> [4033] other            other            other            other           
#> [4037] other            tumor            tumor            tumor           
#> [4041] other            tumor            tumor            tumor           
#> [4045] other            cytotoxic t cell tumor            tumor           
#> [4049] tumor            other            other            tumor           
#> [4053] other            other            other            cytotoxic t cell
#> [4057] tumor            other            tumor            tumor           
#> [4061] other            other            tumor            other           
#> [4065] tumor            other            other            b cell          
#> [4069] other            cytotoxic t cell tumor            other           
#> [4073] other            tumor            tumor            tumor           
#> [4077] other            other            other            tumor           
#> [4081] tumor            tumor            other            other           
#> [4085] other            other            other            tumor           
#> [4089] tumor            tumor            other            other           
#> [4093] tumor            other            other            tumor           
#> [4097] tumor            other            other            other           
#> [4101] tumor            tumor            tumor            other           
#> [4105] cytotoxic t cell other            tumor            tumor           
#> [4109] other            cytotoxic t cell tumor            other           
#> [4113] other            other            other            other           
#> [4117] other            other            other            tumor           
#> [4121] tumor            other            tumor            other           
#> [4125] tumor            tumor            other            other           
#> [4129] other            other            other            other           
#> [4133] other            other            tumor            other           
#> [4137] other            tumor            tumor            other           
#> [4141] other            other            tumor            other           
#> [4145] other            tumor            tumor            tumor           
#> [4149] tumor            tumor            tumor            tumor           
#> [4153] other            other            other            tumor           
#> [4157] tumor            other            tumor            other           
#> [4161] other            other            tumor            other           
#> [4165] tumor            other            other            other           
#> [4169] other            other            other            tumor           
#> [4173] other            tumor            tumor            other           
#> [4177] other            other            tumor            other           
#> [4181] tumor            tumor            tumor            other           
#> [4185] tumor            tumor            other            tumor           
#> [4189] tumor            other            other            tumor           
#> [4193] cytotoxic t cell cytotoxic t cell tumor            other           
#> [4197] tumor            other            other            tumor           
#> [4201] other            tumor            other            tumor           
#> [4205] tumor            tumor            tumor            other           
#> [4209] other            other            other            other           
#> [4213] tumor            tumor            other            other           
#> [4217] other            other            other            tumor           
#> [4221] tumor            tumor            tumor            other           
#> [4225] tumor            tumor            other            tumor           
#> [4229] other            other            tumor            tumor           
#> [4233] tumor            tumor            other            tumor           
#> [4237] tumor            tumor            tumor            other           
#> [4241] other            other            tumor            other           
#> [4245] tumor            other            other            other           
#> [4249] other            other            other            tumor           
#> [4253] tumor            other            tumor            tumor           
#> [4257] tumor            tumor            tumor            tumor           
#> [4261] tumor            other            other            cytotoxic t cell
#> [4265] b cell           other            tumor            other           
#> [4269] cytotoxic t cell other            tumor            cytotoxic t cell
#> [4273] other            other            other            tumor           
#> [4277] other            tumor            tumor            other           
#> [4281] other            other            tumor            tumor           
#> [4285] tumor            other            tumor            tumor           
#> [4289] other            tumor            tumor            other           
#> [4293] tumor            cytotoxic t cell other            other           
#> [4297] tumor            tumor            other            other           
#> [4301] other            tumor            tumor            other           
#> [4305] other            other            other            tumor           
#> [4309] other            tumor            other            b cell          
#> [4313] other            other            other            tumor           
#> [4317] other            tumor            tumor            tumor           
#> [4321] other            tumor            tumor            other           
#> [4325] tumor            other            other            other           
#> [4329] other            other            tumor            other           
#> [4333] tumor            tumor            other            cytotoxic t cell
#> [4337] other            tumor            other            tumor           
#> [4341] tumor            tumor            tumor            other           
#> [4345] tumor            other            tumor            other           
#> [4349] b cell           other            other            tumor           
#> [4353] other            tumor            tumor            tumor           
#> [4357] tumor            other            other            tumor           
#> [4361] tumor            tumor            tumor            other           
#> [4365] other            cytotoxic t cell tumor            tumor           
#> [4369] tumor            tumor            other            tumor           
#> [4373] other            other            other            other           
#> [4377] other            tumor            other            other           
#> [4381] other            other            other            other           
#> [4385] other            tumor            tumor            cytotoxic t cell
#> [4389] other            other            tumor            b cell          
#> [4393] other            b cell           tumor            tumor           
#> [4397] other            tumor            tumor            tumor           
#> [4401] b cell           tumor            other            other           
#> [4405] other            other            other            other           
#> [4409] other            other            other            tumor           
#> [4413] other            tumor            other            cytotoxic t cell
#> [4417] other            tumor            other            other           
#> [4421] tumor            other            other            other           
#> [4425] tumor            tumor            tumor            cytotoxic t cell
#> [4429] other            other            tumor            tumor           
#> [4433] other            other            tumor            other           
#> [4437] other            tumor            tumor            other           
#> [4441] other            tumor            tumor            tumor           
#> [4445] other            b cell           other            other           
#> [4449] other            other            other            other           
#> [4453] other            other            tumor            tumor           
#> [4457] other            other            other            other           
#> [4461] other            other            other            other           
#> [4465] other            other            tumor            other           
#> [4469] tumor            tumor            tumor            b cell          
#> [4473] other            tumor            other            tumor           
#> [4477] tumor            tumor            other            tumor           
#> [4481] other            tumor            tumor            other           
#> [4485] other            tumor            tumor            other           
#> [4489] tumor            tumor            other            b cell          
#> [4493] other            tumor            tumor            other           
#> [4497] tumor            other            other            other           
#> [4501] other            other            other            other           
#> [4505] other            tumor            other            other           
#> [4509] tumor            other            other            cytotoxic t cell
#> [4513] other            cytotoxic t cell other            tumor           
#> [4517] other            other            tumor            other           
#> [4521] tumor            other            other            tumor           
#> [4525] other            other            cytotoxic t cell other           
#> [4529] tumor            other            other            other           
#> [4533] tumor            tumor            tumor            other           
#> [4537] tumor            other            tumor            cytotoxic t cell
#> [4541] other            tumor            other            other           
#> [4545] tumor            tumor            other            other           
#> [4549] tumor            other            other            other           
#> [4553] other            tumor            tumor            other           
#> [4557] other            other            other            other           
#> [4561] tumor            b cell           other            other           
#> [4565] tumor            other            tumor            other           
#> [4569] other            other            tumor            other           
#> [4573] tumor            other            tumor            other           
#> [4577] other            other            other            tumor           
#> [4581] other            other            other            other           
#> [4585] tumor            other            tumor            other           
#> [4589] cytotoxic t cell other            other            tumor           
#> [4593] other            other            tumor            other           
#> [4597] other            other            other            other           
#> [4601] tumor            other            tumor            other           
#> [4605] tumor            other            other            tumor           
#> [4609] tumor            other            tumor            other           
#> [4613] tumor            other            other            other           
#> [4617] tumor            other            other            other           
#> [4621] other            tumor            other            other           
#> [4625] tumor            other            other            other           
#> [4629] tumor            other            tumor            other           
#> [4633] other            other            other            other           
#> [4637] tumor            other            other            b cell          
#> [4641] tumor            tumor            tumor            tumor           
#> [4645] other            other            other            tumor           
#> [4649] tumor            other            other            other           
#> [4653] other            tumor            other            other           
#> [4657] other            other            tumor            tumor           
#> [4661] other            other            other            other           
#> [4665] other            other            other            other           
#> [4669] other            other            tumor            tumor           
#> [4673] other            other            other            other           
#> [4677] other            tumor            other            other           
#> [4681] other            other            tumor            other           
#> [4685] other            other            other            other           
#> [4689] tumor            other            other            tumor           
#> [4693] other            other            tumor            other           
#> [4697] other            other            tumor            other           
#> [4701] other            other            other            other           
#> [4705] other            other            other            other           
#> [4709] other            other            other            other           
#> [4713] other            other            tumor            other           
#> [4717] other            other            tumor            tumor           
#> [4721] other            other            other            other           
#> [4725] tumor            other            tumor            other           
#> [4729] tumor            other            other            other           
#> [4733] other            other            tumor            tumor           
#> [4737] tumor            other            helper t cell    other           
#> [4741] other            other            other            other           
#> [4745] other            other            tumor            tumor           
#> [4749] tumor            other            tumor            tumor           
#> [4753] tumor            other            other            other           
#> [4757] other            other            other            cytotoxic t cell
#> [4761] other            tumor            tumor            other           
#> [4765] other            other            other            other           
#> [4769] tumor            other            other            other           
#> [4773] other            other            other            other           
#> [4777] other            tumor            other            other           
#> [4781] tumor            other            tumor            other           
#> [4785] other            other            other            other           
#> [4789] other            other            tumor            other           
#> [4793] cytotoxic t cell tumor            other            tumor           
#> [4797] tumor            other            other            other           
#> [4801] other            tumor            other            other           
#> [4805] tumor            tumor            other            tumor           
#> [4809] other            other            other            other           
#> [4813] other            other            other            other           
#> [4817] other            tumor            other            other           
#> [4821] other            other            other            tumor           
#> [4825] tumor            other            other            other           
#> [4829] other            other            other            other           
#> [4833] other            tumor            tumor            tumor           
#> [4837] other            other            other            other           
#> [4841] tumor            other            tumor            other           
#> [4845] other            tumor            other            other           
#> [4849] other            other            other            other           
#> [4853] other            other            tumor            other           
#> [4857] other            other            tumor            other           
#> [4861] other            tumor            other            b cell          
#> [4865] tumor            tumor            helper t cell    tumor           
#> [4869] other            tumor            other            other           
#> [4873] other            other            tumor            other           
#> [4877] tumor            other            other            other           
#> [4881] other            other            other            other           
#> [4885] other            tumor            other            other           
#> [4889] other            other            other            other           
#> [4893] other            other            other            other           
#> [4897] other            tumor            other            tumor           
#> [4901] other            other            other            other           
#> [4905] other            tumor            other            tumor           
#> [4909] tumor            other            other            tumor           
#> [4913] tumor            other            other            other           
#> [4917] other            other            other            other           
#> [4921] other            other            other            other           
#> [4925] other            tumor            other            other           
#> [4929] other            other            other            tumor           
#> [4933] other            other            other            other           
#> [4937] other            other            other            other           
#> [4941] other            cytotoxic t cell cytotoxic t cell other           
#> [4945] other            tumor            tumor            tumor           
#> [4949] tumor            tumor            other            tumor           
#> [4953] tumor            other            other            tumor           
#> [4957] other            other            other            other           
#> [4961] other            other            other            other           
#> [4965] other            other            other            other           
#> [4969] other            other            other            other           
#> [4973] other            other            other            tumor           
#> [4977] other            other            other            tumor           
#> [4981] other            tumor            other            tumor           
#> [4985] tumor            cytotoxic t cell other            other           
#> [4989] tumor            other            tumor            other           
#> [4993] other            other            other            other           
#> [4997] other            tumor            other            tumor           
#> [5001] other            other            other            other           
#> [5005] other            other            other            tumor           
#> [5009] macrophage       other            other            other           
#> [5013] tumor            tumor            other            tumor           
#> [5017] other            other            other            tumor           
#> [5021] other            other            tumor            other           
#> [5025] other            tumor            other            other           
#> [5029] tumor            other            tumor            tumor           
#> [5033] tumor            tumor            other            cytotoxic t cell
#> [5037] tumor            other            other            other           
#> [5041] other            other            tumor            other           
#> [5045] other            other            other            other           
#> [5049] other            other            other            other           
#> [5053] other            other            tumor            other           
#> [5057] tumor            other            other            other           
#> [5061] other            other            other            other           
#> [5065] other            other            other            other           
#> [5069] other            tumor            tumor            other           
#> [5073] tumor            other            other            other           
#> [5077] other            other            other            other           
#> [5081] other            other            other            cytotoxic t cell
#> [5085] other            other            other            other           
#> [5089] other            tumor            other            other           
#> [5093] other            other            other            other           
#> [5097] cytotoxic t cell other            other            tumor           
#> [5101] other            other            tumor            tumor           
#> [5105] other            other            other            other           
#> [5109] cytotoxic t cell other            other            tumor           
#> [5113] other            tumor            other            other           
#> [5117] other            tumor            other            tumor           
#> [5121] other            other            other            other           
#> [5125] tumor            other            tumor            other           
#> [5129] other            other            other            other           
#> [5133] other            other            cytotoxic t cell tumor           
#> [5137] other            other            other            other           
#> [5141] other            other            other            tumor           
#> [5145] other            other            other            other           
#> [5149] tumor            other            other            other           
#> [5153] tumor            other            other            other           
#> [5157] other            other            tumor            tumor           
#> [5161] other            other            other            other           
#> [5165] tumor            other            other            other           
#> [5169] other            other            other            tumor           
#> [5173] other            other            other            other           
#> [5177] other            other            other            tumor           
#> [5181] other            other            other            other           
#> [5185] other            other            other            other           
#> [5189] other            tumor            tumor            tumor           
#> [5193] other            other            tumor            other           
#> [5197] other            tumor            tumor            other           
#> [5201] other            other            tumor            other           
#> [5205] other            other            other            tumor           
#> [5209] other            tumor            other            other           
#> [5213] other            tumor            tumor            other           
#> [5217] other            other            other            other           
#> [5221] other            other            other            other           
#> [5225] other            other            other            other           
#> [5229] other            tumor            other            tumor           
#> [5233] other            other            other            other           
#> [5237] other            other            other            other           
#> [5241] tumor            other            tumor            other           
#> [5245] other            other            other            other           
#> [5249] tumor            other            tumor            tumor           
#> [5253] other            tumor            other            tumor           
#> [5257] cytotoxic t cell tumor            other            other           
#> [5261] other            tumor            other            other           
#> [5265] other            other            other            tumor           
#> [5269] other            other            other            tumor           
#> [5273] tumor            other            other            tumor           
#> [5277] other            other            other            other           
#> [5281] other            other            other            other           
#> [5285] other            other            other            other           
#> [5289] other            other            cytotoxic t cell other           
#> [5293] other            other            cytotoxic t cell other           
#> [5297] other            other            other            other           
#> [5301] other            other            other            other           
#> [5305] other            other            tumor            other           
#> [5309] other            tumor            other            other           
#> [5313] tumor            other            cytotoxic t cell other           
#> [5317] other            cytotoxic t cell tumor            tumor           
#> [5321] other            other            other            other           
#> [5325] other            other            other            other           
#> [5329] other            tumor            other            other           
#> [5333] b cell           other            other            other           
#> [5337] tumor            other            cytotoxic t cell other           
#> [5341] other            tumor            other            other           
#> [5345] other            other            other            tumor           
#> [5349] other            other            tumor            tumor           
#> [5353] other            other            tumor            other           
#> [5357] other            other            tumor            other           
#> [5361] tumor            other            tumor            tumor           
#> [5365] tumor            other            other            other           
#> [5369] other            other            tumor            tumor           
#> [5373] other            other            other            other           
#> [5377] other            other            other            other           
#> [5381] other            tumor            other            other           
#> [5385] other            other            other            tumor           
#> [5389] other            other            tumor            tumor           
#> [5393] other            other            other            other           
#> [5397] other            other            other            tumor           
#> [5401] other            other            tumor            other           
#> [5405] other            other            other            other           
#> [5409] tumor            other            tumor            other           
#> [5413] other            tumor            other            other           
#> [5417] other            other            other            other           
#> [5421] other            other            tumor            other           
#> [5425] other            cytotoxic t cell other            other           
#> [5429] other            other            tumor            other           
#> [5433] other            other            other            other           
#> [5437] other            other            tumor            other           
#> [5441] other            other            other            other           
#> [5445] other            other            other            other           
#> [5449] other            other            other            cytotoxic t cell
#> [5453] other            other            other            other           
#> [5457] tumor            other            tumor            other           
#> [5461] other            other            other            other           
#> [5465] other            other            other            other           
#> [5469] other            other            other            other           
#> [5473] other            other            other            other           
#> [5477] tumor            other            other            other           
#> [5481] tumor            other            other            tumor           
#> [5485] tumor            other            other            other           
#> [5489] tumor            other            other            other           
#> [5493] other            other            other            other           
#> [5497] cytotoxic t cell other            other            other           
#> [5501] other            tumor            other            other           
#> [5505] other            other            other            other           
#> [5509] other            other            other            other           
#> [5513] other            other            other            other           
#> [5517] other            other            other            tumor           
#> [5521] tumor            other            cytotoxic t cell other           
#> [5525] tumor            tumor            other            other           
#> [5529] other            other            tumor            other           
#> [5533] other            other            cytotoxic t cell other           
#> [5537] other            other            other            other           
#> [5541] other            other            other            tumor           
#> [5545] other            other            tumor            other           
#> [5549] tumor            tumor            other            other           
#> [5553] other            tumor            other            other           
#> [5557] other            cytotoxic t cell tumor            tumor           
#> [5561] other            other            other            other           
#> [5565] other            other            other            other           
#> [5569] tumor            other            other            other           
#> [5573] other            other            other            other           
#> [5577] other            other            tumor            other           
#> [5581] other            other            other            tumor           
#> [5585] tumor            other            other            other           
#> [5589] other            other            other            other           
#> [5593] other            other            other            other           
#> [5597] other            other            other            other           
#> [5601] other            tumor            other            other           
#> [5605] other            other            other            tumor           
#> [5609] other            other            other            other           
#> [5613] other            other            tumor            other           
#> [5617] other            other            other            other           
#> [5621] other            tumor            other            other           
#> [5625] other            other            other            other           
#> [5629] other            other            other            other           
#> [5633] other            other            other            other           
#> [5637] other            other            other            other           
#> [5641] other            other            other            other           
#> [5645] tumor            other            other            other           
#> [5649] other            tumor            other            other           
#> [5653] other            other            other            other           
#> [5657] other            tumor            other            other           
#> [5661] other            tumor            other            other           
#> [5665] other            other            other            other           
#> [5669] other            other            tumor            other           
#> [5673] other            other            other            other           
#> [5677] other            other            tumor            other           
#> [5681] other            other            other            other           
#> [5685] other            other            other            other           
#> [5689] other            tumor            other            other           
#> [5693] other            other            tumor            other           
#> [5697] other            other            other            other           
#> [5701] other            other            other            other           
#> [5705] other            other            other            other           
#> [5709] other            other            other            other           
#> [5713] other            b cell           other            other           
#> [5717] other            other            other            tumor           
#> [5721] other            other            other            other           
#> [5725] other            other            other            cytotoxic t cell
#> [5729] other            other            other            other           
#> [5733] other            other            other            other           
#> [5737] other            other            other            other           
#> [5741] other            other            other            other           
#> [5745] other            other            cytotoxic t cell other           
#> [5749] tumor            other            tumor            other           
#> [5753] other            other            other            other           
#> [5757] other            other            cytotoxic t cell other           
#> [5761] tumor            other            other            other           
#> [5765] other            other            other            other           
#> [5769] other            other            other            other           
#> [5773] other            other            other            other           
#> [5777] other            tumor            other            tumor           
#> [5781] other            other            other            other           
#> [5785] other            other            tumor            other           
#> [5789] tumor            other            tumor            cytotoxic t cell
#> [5793] other            helper t cell    other            other           
#> [5797] other            other            other            other           
#> [5801] other            other            other            other           
#> [5805] other            other            other            other           
#> [5809] other            other            other            other           
#> [5813] other            other            other            other           
#> [5817] other            other            other            other           
#> [5821] other            other            other            other           
#> [5825] other            other            other            b cell          
#> [5829] tumor            other            other            other           
#> [5833] other            cytotoxic t cell other            other           
#> [5837] other            other            other            other           
#> [5841] other            other            other            other           
#> [5845] other            other            other            other           
#> [5849] other            other            tumor            other           
#> [5853] other            other            other            other           
#> [5857] other            other            other            other           
#> [5861] other            other            other            other           
#> [5865] other            other            other            other           
#> [5869] tumor            other            other            other           
#> [5873] other            other            other            other           
#> [5877] other            tumor            other            other           
#> [5881] tumor            other            cytotoxic t cell other           
#> [5885] other            tumor            other            other           
#> [5889] other            other            other            other           
#> [5893] other            tumor            other            tumor           
#> [5897] other            other            other            cytotoxic t cell
#> [5901] other            other            helper t cell    other           
#> [5905] other            other            other            other           
#> [5909] helper t cell    other            other            other           
#> [5913] other            other            other            helper t cell   
#> [5917] other            other            other            other           
#> [5921] other            tumor            other            other           
#> [5925] other            other            other            other           
#> [5929] other            other            other            other           
#> [5933] other            other            other            other           
#> [5937] other            other            other            other           
#> [5941] other            other            other            other           
#> [5945] other            other            other            other           
#> [5949] other            other            other            other           
#> [5953] other            other            tumor            other           
#> [5957] tumor            other            other            other           
#> [5961] other            other            other            other           
#> [5965] other            other            other            other           
#> [5969] other            other            tumor            other           
#> [5973] other            other            other            other           
#> [5977] other            other            other            other           
#> [5981] other            other            other            other           
#> [5985] other            other            other            other           
#> [5989] other            other            other            other           
#> [5993] other            other            other            other           
#> [5997] other            other            other            other           
#> [6001] other            other            other            other           
#> [6005] other            other            tumor            other           
#> [6009] other            other            other            cytotoxic t cell
#> [6013] b cell           other            other            other           
#> [6017] other            other            other            other           
#> [6021] other            other            other            other           
#> [6025] other            other            other            other           
#> [6029] other            other            tumor            other           
#> [6033] tumor            other            other            other           
#> [6037] other            other            other            other           
#> [6041] other            other            other            other           
#> [6045] other            other            other            other           
#> [6049] other            other            tumor            other           
#> [6053] other            other            other            other           
#> [6057] tumor            other            tumor            other           
#> [6061] tumor            other            other            tumor           
#> [6065] other            other            other            other           
#> [6069] other            cytotoxic t cell other            other           
#> [6073] other            other            other            other           
#> [6077] other            tumor            other            other           
#> [6081] other            tumor            other            other           
#> [6085] other            other            other            other           
#> [6089] other            other            other            other           
#> [6093] tumor            other            other            other           
#> [6097] other            other            other            other           
#> [6101] other            other            other            other           
#> [6105] tumor            cytotoxic t cell other            other           
#> [6109] other            tumor            other            other           
#> [6113] other            other            other            other           
#> [6117] other            other            other            other           
#> [6121] other            other            tumor            other           
#> [6125] tumor            other            other            other           
#> [6129] tumor            other            other            other           
#> [6133] other            tumor            b cell           other           
#> [6137] other            other            other            other           
#> [6141] other            tumor            other            b cell          
#> [6145] other            other            other            other           
#> [6149] other            other            other            other           
#> [6153] other            other            other            other           
#> [6157] other            other            tumor            tumor           
#> [6161] other            other            other            tumor           
#> [6165] other            other            other            other           
#> [6169] other            other            other            other           
#> [6173] other            other            other            other           
#> [6177] other            other            cytotoxic t cell tumor           
#> [6181] other            other            other            tumor           
#> [6185] other            other            other            other           
#> [6189] other            other            other            cytotoxic t cell
#> [6193] other            other            other            other           
#> [6197] other            other            other            other           
#> [6201] other            other            other            other           
#> [6205] other            other            other            other           
#> [6209] other            other            other            macrophage      
#> [6213] other            other            other            other           
#> [6217] other            other            tumor            other           
#> [6221] other            tumor            other            other           
#> [6225] other            other            other            other           
#> [6229] other            other            other            tumor           
#> [6233] tumor            other            other            other           
#> [6237] other            other            other            other           
#> [6241] other            tumor            other            other           
#> [6245] other            other            other            other           
#> [6249] cytotoxic t cell other            cytotoxic t cell other           
#> [6253] other            other            tumor            other           
#> [6257] other            tumor            other            other           
#> [6261] other            tumor            other            other           
#> [6265] other            other            other            other           
#> [6269] cytotoxic t cell other            other            other           
#> [6273] other            other            other            other           
#> [6277] cytotoxic t cell other            other            other           
#> [6281] other            tumor            other            other           
#> [6285] other            other            tumor            other           
#> [6289] other            other            tumor            other           
#> [6293] tumor            other            tumor            tumor           
#> [6297] other            cytotoxic t cell other            other           
#> [6301] tumor            other            other            tumor           
#> [6305] other            tumor            other            other           
#> [6309] other            cytotoxic t cell other            other           
#> [6313] other            other            tumor            other           
#> [6317] other            other            other            other           
#> [6321] other            other            other            other           
#> [6325] other            b cell           other            other           
#> [6329] other            other            other            other           
#> [6333] other            other            other            tumor           
#> [6337] other            other            other            other           
#> [6341] other            other            other            other           
#> [6345] tumor            tumor            tumor            other           
#> [6349] other            other            tumor            other           
#> [6353] tumor            other            other            other           
#> [6357] tumor            other            other            other           
#> [6361] other            tumor            other            other           
#> [6365] other            other            other            b cell          
#> [6369] other            other            other            tumor           
#> [6373] other            tumor            other            other           
#> [6377] other            other            other            other           
#> [6381] other            other            other            other           
#> [6385] other            other            other            other           
#> [6389] other            other            tumor            other           
#> [6393] other            b cell           other            other           
#> [6397] other            other            other            other           
#> [6401] other            other            other            other           
#> [6405] tumor            other            other            other           
#> [6409] other            other            cytotoxic t cell cytotoxic t cell
#> [6413] other            other            other            other           
#> [6417] other            other            other            other           
#> [6421] other            other            cytotoxic t cell other           
#> [6425] other            other            other            other           
#> [6429] tumor            other            other            tumor           
#> [6433] other            other            other            other           
#> [6437] other            other            other            other           
#> [6441] other            other            other            other           
#> [6445] tumor            other            other            other           
#> [6449] other            other            macrophage       tumor           
#> [6453] other            other            other            other           
#> [6457] other            other            other            tumor           
#> [6461] tumor            tumor            other            tumor           
#> [6465] other            other            other            other           
#> [6469] other            other            cytotoxic t cell cytotoxic t cell
#> [6473] other            tumor            tumor            tumor           
#> [6477] other            other            tumor            other           
#> [6481] other            tumor            other            other           
#> [6485] tumor            other            tumor            tumor           
#> [6489] other            other            tumor            tumor           
#> [6493] other            other            tumor            other           
#> [6497] other            other            other            other           
#> [6501] other            other            other            other           
#> [6505] other            other            tumor            other           
#> [6509] other            other            other            other           
#> [6513] tumor            other            tumor            other           
#> [6517] other            other            other            other           
#> [6521] other            other            tumor            other           
#> [6525] other            other            other            other           
#> [6529] other            other            other            tumor           
#> [6533] other            other            cytotoxic t cell other           
#> [6537] other            other            other            tumor           
#> [6541] other            other            other            other           
#> [6545] other            cytotoxic t cell tumor            tumor           
#> [6549] other            other            other            other           
#> [6553] other            other            other            tumor           
#> [6557] other            other            other            other           
#> [6561] other            other            tumor            tumor           
#> [6565] cytotoxic t cell other            cytotoxic t cell cytotoxic t cell
#> [6569] tumor            other            other            other           
#> [6573] other            tumor            other            other           
#> [6577] other            tumor            tumor            other           
#> [6581] tumor            other            tumor            other           
#> [6585] tumor            other            tumor            other           
#> [6589] other            other            other            other           
#> [6593] tumor            tumor            other            other           
#> [6597] other            other            tumor            tumor           
#> [6601] tumor            other            other            other           
#> [6605] b cell           other            other            other           
#> [6609] other            tumor            other            other           
#> [6613] other            tumor            other            other           
#> [6617] other            other            other            tumor           
#> [6621] other            other            tumor            other           
#> [6625] tumor            tumor            tumor            tumor           
#> [6629] b cell           other            other            other           
#> [6633] cytotoxic t cell tumor            other            tumor           
#> [6637] tumor            other            other            other           
#> [6641] tumor            cytotoxic t cell tumor            tumor           
#> [6645] other            other            other            other           
#> [6649] tumor            cytotoxic t cell tumor            tumor           
#> [6653] tumor            other            tumor            tumor           
#> [6657] tumor            other            other            other           
#> [6661] tumor            other            tumor            tumor           
#> [6665] cytotoxic t cell other            other            other           
#> [6669] tumor            b cell           tumor            tumor           
#> [6673] b cell           other            tumor            other           
#> [6677] tumor            tumor            other            tumor           
#> [6681] other            tumor            cytotoxic t cell tumor           
#> [6685] other            other            other            other           
#> [6689] other            other            other            tumor           
#> [6693] tumor            other            other            other           
#> [6697] other            other            other            tumor           
#> [6701] cytotoxic t cell other            tumor            other           
#> [6705] cytotoxic t cell other            other            other           
#> [6709] other            other            other            other           
#> [6713] other            other            other            other           
#> [6717] other            tumor            other            other           
#> [6721] tumor            other            other            cytotoxic t cell
#> [6725] cytotoxic t cell cytotoxic t cell other            other           
#> [6729] other            other            other            tumor           
#> [6733] other            other            other            other           
#> [6737] tumor            tumor            other            other           
#> [6741] other            tumor            tumor            other           
#> [6745] other            tumor            tumor            other           
#> [6749] other            other            other            tumor           
#> [6753] other            cytotoxic t cell b cell           other           
#> [6757] tumor            other            tumor            other           
#> [6761] other            tumor            tumor            other           
#> [6765] tumor            other            other            tumor           
#> [6769] cytotoxic t cell other            cytotoxic t cell other           
#> [6773] tumor            other            b cell           tumor           
#> [6777] other            other            other            other           
#> [6781] b cell           other            tumor            other           
#> [6785] other            tumor            tumor            other           
#> [6789] tumor            other            tumor            tumor           
#> [6793] other            tumor            other            other           
#> [6797] other            tumor            other            other           
#> [6801] other            tumor            other            other           
#> [6805] other            other            other            tumor           
#> [6809] other            other            tumor            other           
#> [6813] tumor            other            other            other           
#> [6817] tumor            other            other            other           
#> [6821] tumor            other            cytotoxic t cell tumor           
#> [6825] other            tumor            tumor            tumor           
#> [6829] tumor            cytotoxic t cell other            other           
#> [6833] other            other            other            other           
#> [6837] tumor            other            other            other           
#> [6841] other            other            other            tumor           
#> [6845] other            tumor            tumor            other           
#> [6849] other            other            other            other           
#> [6853] tumor            other            tumor            other           
#> [6857] macrophage       other            tumor            other           
#> [6861] other            other            other            tumor           
#> [6865] other            other            other            tumor           
#> [6869] other            other            other            tumor           
#> [6873] tumor            other            other            other           
#> [6877] other            tumor            other            tumor           
#> [6881] other            other            tumor            other           
#> [6885] other            other            other            other           
#> [6889] other            other            other            other           
#> [6893] other            other            other            other           
#> [6897] other            other            other            tumor           
#> [6901] other            tumor            other            other           
#> [6905] tumor            other            other            other           
#> [6909] other            other            other            other           
#> [6913] other            other            other            other           
#> [6917] other            tumor            other            other           
#> [6921] other            other            other            tumor           
#> [6925] other            other            other            other           
#> [6929] other            other            other            other           
#> [6933] other            cytotoxic t cell tumor            other           
#> [6937] other            other            other            other           
#> [6941] other            other            other            other           
#> [6945] tumor            other            other            other           
#> [6949] other            cytotoxic t cell other            other           
#> [6953] other            other            macrophage       other           
#> [6957] other            other            other            b cell          
#> [6961] other            tumor            tumor            other           
#> [6965] other            other            other            other           
#> [6969] other            other            other            other           
#> [6973] other            other            other            other           
#> [6977] other            other            other            other           
#> [6981] other            other            other            tumor           
#> [6985] tumor            other            other            other           
#> [6989] other            other            cytotoxic t cell other           
#> [6993] other            tumor            other            other           
#> [6997] tumor            other            cytotoxic t cell tumor           
#> [7001] tumor            other            other            other           
#> [7005] other            other            other            tumor           
#> [7009] other            other            other            other           
#> [7013] other            tumor            other            other           
#> [7017] tumor            other            other            tumor           
#> [7021] tumor            b cell           other            b cell          
#> [7025] tumor            other            other            other           
#> [7029] tumor            other            tumor            tumor           
#> [7033] other            other            other            other           
#> [7037] tumor            other            tumor            tumor           
#> [7041] other            cytotoxic t cell tumor            tumor           
#> [7045] tumor            tumor            cytotoxic t cell other           
#> [7049] other            tumor            tumor            other           
#> [7053] other            other            other            tumor           
#> [7057] other            tumor            other            other           
#> [7061] tumor            tumor            other            other           
#> [7065] other            cytotoxic t cell other            other           
#> [7069] tumor            tumor            other            tumor           
#> [7073] tumor            other            b cell           other           
#> [7077] other            other            tumor            other           
#> [7081] tumor            other            cytotoxic t cell other           
#> [7085] other            tumor            other            other           
#> [7089] tumor            other            other            other           
#> [7093] tumor            tumor            other            other           
#> [7097] tumor            other            other            other           
#> [7101] tumor            other            tumor            tumor           
#> [7105] other            tumor            tumor            other           
#> [7109] tumor            tumor            cytotoxic t cell tumor           
#> [7113] other            other            other            other           
#> [7117] tumor            other            tumor            tumor           
#> [7121] other            other            other            tumor           
#> [7125] other            other            other            other           
#> [7129] cytotoxic t cell other            other            other           
#> [7133] other            tumor            tumor            other           
#> [7137] tumor            tumor            other            cytotoxic t cell
#> [7141] tumor            other            cytotoxic t cell other           
#> [7145] tumor            other            tumor            other           
#> [7149] tumor            other            tumor            tumor           
#> [7153] tumor            tumor            other            other           
#> [7157] other            other            tumor            other           
#> [7161] tumor            tumor            tumor            other           
#> [7165] other            other            other            tumor           
#> [7169] other            tumor            other            other           
#> [7173] tumor            other            tumor            tumor           
#> [7177] other            tumor            other            tumor           
#> [7181] other            tumor            other            other           
#> [7185] tumor            tumor            tumor            tumor           
#> [7189] tumor            tumor            tumor            tumor           
#> [7193] other            other            tumor            macrophage      
#> [7197] other            cytotoxic t cell tumor            tumor           
#> [7201] tumor            other            other            tumor           
#> [7205] other            other            tumor            other           
#> [7209] tumor            tumor            tumor            tumor           
#> [7213] tumor            other            other            tumor           
#> [7217] tumor            tumor            tumor            other           
#> [7221] tumor            other            other            tumor           
#> [7225] tumor            tumor            tumor            other           
#> [7229] other            tumor            other            other           
#> [7233] tumor            tumor            tumor            macrophage      
#> [7237] tumor            other            other            other           
#> [7241] tumor            other            other            other           
#> [7245] tumor            tumor            tumor            other           
#> [7249] tumor            other            other            other           
#> [7253] tumor            tumor            tumor            other           
#> [7257] other            other            tumor            tumor           
#> [7261] other            other            tumor            other           
#> [7265] tumor            other            other            tumor           
#> [7269] other            tumor            other            other           
#> [7273] cytotoxic t cell tumor            tumor            tumor           
#> [7277] other            other            tumor            tumor           
#> [7281] tumor            tumor            other            other           
#> [7285] other            tumor            other            tumor           
#> [7289] tumor            other            other            tumor           
#> [7293] tumor            other            tumor            other           
#> [7297] other            other            other            tumor           
#> [7301] tumor            tumor            other            tumor           
#> [7305] tumor            other            other            tumor           
#> [7309] tumor            other            other            tumor           
#> [7313] tumor            other            other            other           
#> [7317] cytotoxic t cell other            tumor            tumor           
#> [7321] tumor            other            tumor            tumor           
#> [7325] tumor            tumor            tumor            other           
#> [7329] other            tumor            tumor            other           
#> [7333] tumor            tumor            tumor            tumor           
#> [7337] other            cytotoxic t cell other            cytotoxic t cell
#> [7341] other            other            tumor            other           
#> [7345] tumor            tumor            tumor            tumor           
#> [7349] cytotoxic t cell other            tumor            tumor           
#> [7353] other            other            tumor            tumor           
#> [7357] cytotoxic t cell tumor            tumor            tumor           
#> [7361] other            tumor            tumor            helper t cell   
#> [7365] other            tumor            tumor            tumor           
#> [7369] other            tumor            tumor            other           
#> [7373] tumor            other            tumor            tumor           
#> [7377] tumor            other            tumor            other           
#> [7381] other            tumor            tumor            other           
#> [7385] other            tumor            tumor            other           
#> [7389] other            tumor            other            tumor           
#> [7393] tumor            tumor            other            other           
#> [7397] other            other            other            other           
#> [7401] other            other            other            other           
#> [7405] other            cytotoxic t cell other            tumor           
#> [7409] other            tumor            other            other           
#> [7413] tumor            tumor            tumor            tumor           
#> [7417] other            tumor            other            tumor           
#> [7421] other            other            other            tumor           
#> [7425] other            tumor            other            other           
#> [7429] other            other            other            other           
#> [7433] other            other            other            other           
#> [7437] tumor            tumor            tumor            tumor           
#> [7441] tumor            tumor            tumor            tumor           
#> [7445] tumor            tumor            tumor            tumor           
#> [7449] tumor            tumor            cytotoxic t cell tumor           
#> [7453] tumor            other            other            other           
#> [7457] tumor            other            other            tumor           
#> [7461] tumor            other            other           
#> Levels: b cell cytotoxic t cell helper t cell macrophage other tumor
biv_kamp <- kamp(ppp_obj = pp_biv_data,
                 rvals = seq(0, 100, by = 10),
                 univariate = FALSE,
                 marksvar1 = "helper t cell",
                 marksvar2 = "cytotoxic t cell")
#> The point pattern object has more than 10000 points. Switching to border correction
head(biv_kamp)
#> # A tibble: 6 × 5
#>       r      k theo_csr kamp_csr  kamp
#>   <dbl>  <dbl>    <dbl>    <dbl> <dbl>
#> 1     0     0        0        0     0 
#> 2    10   663.     314.     521.  142.
#> 3    20  2667.    1257.    2108.  559.
#> 4    30  7386.    2827.    4527. 2859.
#> 5    40  8745.    5027.    7727. 1017.
#> 6    50 13191.    7854.   11713. 1478.
biv_kamp %>%
  ggplot(aes(x = r)) +
  geom_line(aes(y = theo_csr, color = "theo_csr", linetype = "theo_csr"), size = 1) +
  geom_line(aes(y = kamp, color = "kamp", linetype = "kamp"), size = 1) +
  geom_line(aes(y = k, color = "k", linetype = "k"), size = 1) +
  geom_hline(yintercept = 0, linetype = "dashed", color = "gray") +
  scale_color_manual(
    values = c(
      "theo_csr" = "black",
      "kamp" = "blue",
      "k" = "red"
    )
  ) +
  scale_linetype_manual(
    values = c(
      "theo_csr" = "solid",
      "kamp" = "dotted",
      "k" = "dotted"
    )
  ) +
  labs(
    title = "Bivariate KAMP Expectation",
    x = "r",
    y = "Value",
    color = "Series",
    linetype = "Series"
  ) +
  theme_minimal()

Variance

biv_kamp_var <- kamp(ppp_obj = pp_biv_data,
                     rvals = seq(0, 100, by = 10),
                     univariate = FALSE,
                     marksvar1 = "helper t cell",
                     marksvar2 = "cytotoxic t cell",
                     variance = TRUE)
#> The point pattern object has more than 10000 points. Switching to border correction
#>  ■■■■                               9% |  ETA:  1m
#>  ■■■■■■                            18% |  ETA:  1m
#>  ■■■■■■■■■                         27% |  ETA:  1m
#>  ■■■■■■■■■■■■                      36% |  ETA:  1m
#>  ■■■■■■■■■■■■■■■                   45% |  ETA: 44s
#>  ■■■■■■■■■■■■■■■■■                 55% |  ETA: 36s
#>  ■■■■■■■■■■■■■■■■■■■■              64% |  ETA: 29s
#>  ■■■■■■■■■■■■■■■■■■■■■■■           73% |  ETA: 22s
#>  ■■■■■■■■■■■■■■■■■■■■■■■■■■        82% |  ETA: 15s
#>  ■■■■■■■■■■■■■■■■■■■■■■■■■■■■      91% |  ETA:  7s
head(biv_kamp_var)
#> # A tibble: 6 × 6
#>       r      k theo_csr kamp_csr      var   pvalue
#>   <dbl>  <dbl>    <dbl>    <dbl>    <dbl>    <dbl>
#> 1     0     0        0        0        0  NaN     
#> 2    10   663.     314.     523.  173055.   0.368 
#> 3    20  2667.    1257.    2108.  716375.   0.255 
#> 4    30  7386.    2827.    4527. 1609555.   0.0121
#> 5    40  8745.    5027.    7727. 2907985.   0.275 
#> 6    50 13191.    7854.   11713. 4691046.   0.248
biv_kamp_var %>%
  ggplot(aes(x = r, y = var)) +
  geom_line() +
  geom_hline(yintercept = 0, linetype = "dashed", color = "blue") +
  labs(title = "Bivariate KAMP Variance", x = "r", y = "Variance") +
  theme_minimal()

KAMP-lite (Thinning)

KAMP-lite refers to running KAMP with a thinned point pattern using thin = TRUE and specifying p_thin between 0 and 1. This helps with performance on large datasets.

Univariate

Expectation

ids <- unique(ovarian_df$sample_id)
marksvar <- "immune"
univ_data <- ovarian_df %>% filter(sample_id == ids[1])

w <- convexhull.xy(univ_data$x, univ_data$y)
pp_univ_data <- ppp(univ_data$x, univ_data$y, window = w, marks = univ_data[[marksvar]])


univ_kamp_lite <- kamp(ppp_obj = pp_univ_data,
                       rvals = seq(0, 100, by = 10),
                       univariate = TRUE,
                       marksvar1 = "immune",
                       thin = TRUE,
                       p_thin = 0.3)
#> The point pattern object has more than 10000 points. Switching to border correction
univ_kamp_lite
#> # A tibble: 11 × 5
#>        r      k theo_csr kamp_csr   kamp
#>    <dbl>  <dbl>    <dbl>    <dbl>  <dbl>
#>  1     0     0        0        0      0 
#>  2    10  2162.     314.     524.  1638.
#>  3    20  5468.    1257.    2118.  3350.
#>  4    30  9179.    2827.    4499.  4680.
#>  5    40 13995.    5027.    7664.  6331.
#>  6    50 19611.    7854.   11600.  8011.
#>  7    60 26824.   11310.   16325. 10499.
#>  8    70 35349.   15394.   21893. 13456.
#>  9    80 43318.   20106.   28137. 15181.
#> 10    90 51432.   25447.   35125. 16307.
#> 11   100 59610.   31416.   42752. 16858.
univ_kamp_lite %>%
  ggplot(aes(x = r)) +
  geom_line(aes(y = theo_csr, color = "theo_csr", linetype = "theo_csr"), size = 1) +
  geom_line(aes(y = kamp, color = "kamp", linetype = "kamp"), size = 1) +
  geom_line(aes(y = k, color = "k", linetype = "k"), size = 1) +
  geom_hline(yintercept = 0, linetype = "dashed", color = "gray") +
  scale_color_manual(
    values = c(
      "theo_csr" = "black",
      "kamp" = "blue",
      "k" = "red"
    )
  ) +
  scale_linetype_manual(
    values = c(
      "theo_csr" = "solid",
      "kamp" = "dotted",
      "k" = "dotted"
    )
  ) +
  labs(
    title = "Univariate KAMP-lite Expectation",
    x = "r",
    y = "Value",
    color = "Series",
    linetype = "Series"
  ) +
  theme_minimal()

Variance

univ_kamp_lite_var <- kamp(ppp_obj = pp_univ_data,
                            rvals = seq(0, 100, by = 10),
                            univariate = TRUE,
                            marksvar1 = "immune",
                            thin = TRUE,
                            p_thin = 0.3,
                            variance = TRUE) # should display a warning message
#> Variance calculation is not supported with KAMP lite
#> Variance calculation with KAMP lite is not recommended. Variance will still be computed, but interpret with caution.
#> The point pattern object has more than 10000 points. Switching to border correction
#>  ■■■■                               9% |  ETA: 36s
#>  ■■■■■■                            18% |  ETA: 32s
#>  ■■■■■■■■■                         27% |  ETA: 29s
#>  ■■■■■■■■■■■■                      36% |  ETA: 25s
#>  ■■■■■■■■■■■■■■■                   45% |  ETA: 22s
#>  ■■■■■■■■■■■■■■■■■                 55% |  ETA: 18s
#>  ■■■■■■■■■■■■■■■■■■■■              64% |  ETA: 14s
#>  ■■■■■■■■■■■■■■■■■■■■■■■           73% |  ETA: 11s
#>  ■■■■■■■■■■■■■■■■■■■■■■■■■■        82% |  ETA:  7s
#>  ■■■■■■■■■■■■■■■■■■■■■■■■■■■■      91% |  ETA:  4s
univ_kamp_lite_var
#> # A tibble: 11 × 7
#>        r      k theo_csr kamp_csr   kamp      var     pvalue
#>    <dbl>  <dbl>    <dbl>    <dbl>  <dbl>    <dbl>      <dbl>
#>  1     0     0        0        0      0        0  NaN       
#>  2    10  1964.     314.     530.  1434.   41463.   9.52e-13
#>  3    20  6079.    1257.    2112.  3968.  172314.   5.98e-22
#>  4    30 11184.    2827.    4538.  6647.  399411.   3.61e-26
#>  5    40 16411.    5027.    7745.  8666.  744554.   4.91e-24
#>  6    50 20947.    7854.   11735.  9212. 1239598.   6.46e-17
#>  7    60 27720.   11310.   16462. 11258. 1928490.   2.60e-16
#>  8    70 35789.   15394.   22025. 13764. 2869955.   2.24e-16
#>  9    80 43263.   20106.   28282. 14981. 4070528.   5.63e-14
#> 10    90 51724.   25447.   35275. 16449. 5615689.   1.94e-12
#> 11   100 60087.   31416.   42967. 17120. 7546680.   2.30e-10

Bivariate

ids <- unique(ovarian_df$sample_id)
biv_data <- ovarian_df %>% 
  filter(sample_id == ids[1]) #%>%
  #filter(phenotype %in% c("helper t cell", "cytotoxic t cell", "other")) %>%
  #droplevels()

marksvar <- "phenotype"

head(biv_data)
#>   cell_id                                           sample_id       x       y
#> 1       1 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20592.9 34524.4
#> 2       2 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20859.3 34524.4
#> 3       3 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20591.4 34530.4
#> 4       4 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20744.7 34528.9
#> 5       5 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20419.8 34540.8
#> 6       6 030120 P9HuP6 TMA 1-B_Core[1,1,H]_[20633,35348].im3 20741.7 34542.3
#>       immune phenotype
#> 1 background     other
#> 2 background     other
#> 3 background     tumor
#> 4 background     tumor
#> 5 background     other
#> 6 background     tumor
w <- convexhull.xy(biv_data$x, biv_data$y)
pp_biv_data <- ppp(biv_data$x, biv_data$y, window = w, marks = biv_data[[marksvar]])

Expectation

biv_kamp_lite <- kamp(ppp_obj = pp_biv_data,
                 rvals = seq(0, 100, by = 10),
                 univariate = FALSE,
                 marksvar1 = "helper t cell",
                 marksvar2 = "cytotoxic t cell",
                 thin = TRUE,
                 p_thin = 0.3)
#> The point pattern object has more than 10000 points. Switching to border correction
head(biv_kamp_lite)
#> # A tibble: 6 × 5
#>       r      k theo_csr kamp_csr  kamp
#>   <dbl>  <dbl>    <dbl>    <dbl> <dbl>
#> 1     0     0        0        0     0 
#> 2    10   759.     314.     528.  231.
#> 3    20  3830.    1257.    2115. 1715.
#> 4    30 10028.    2827.    4543. 5484.
#> 5    40 10028.    5027.    7720. 2308.
#> 6    50 13948.    7854.   11725. 2223.
biv_kamp_lite %>%
  ggplot(aes(x = r)) +
  geom_line(aes(y = theo_csr, color = "theo_csr", linetype = "theo_csr"), size = 1) +
  geom_line(aes(y = kamp, color = "kamp", linetype = "kamp"), size = 1) +
  geom_line(aes(y = k, color = "k", linetype = "k"), size = 1) +
  geom_hline(yintercept = 0, linetype = "dashed", color = "gray") +
  scale_color_manual(
    values = c(
      "theo_csr" = "black",
      "kamp" = "blue",
      "k" = "red"
    )
  ) +
  scale_linetype_manual(
    values = c(
      "theo_csr" = "solid",
      "kamp" = "dotted",
      "k" = "dotted"
    )
  ) +
  labs(
    title = "Bivariate KAMP-lite Expectation",
    x = "r",
    y = "Value",
    color = "Series",
    linetype = "Series"
  ) +
  theme_minimal()

Variance

biv_kamp_lite_var <- kamp(ppp_obj = pp_biv_data,
                          rvals = seq(0, 100, by = 10),
                          univariate = FALSE,
                          marksvar1 = "helper t cell",
                          marksvar2 = "cytotoxic t cell",
                          variance = TRUE,
                          thin = TRUE,
                          p_thin = 0.3) # should display a warning message
#> Variance calculation is not supported with KAMP lite
#> Variance calculation with KAMP lite is not recommended. Variance will still be computed, but interpret with caution.
#> The point pattern object has more than 10000 points. Switching to border correction
#>  ■■■■                               9% |  ETA: 35s
#>  ■■■■■■                            18% |  ETA: 32s
#>  ■■■■■■■■■                         27% |  ETA: 28s
#>  ■■■■■■■■■■■■                      36% |  ETA: 24s
#>  ■■■■■■■■■■■■■■■                   45% |  ETA: 21s
#>  ■■■■■■■■■■■■■■■■■                 55% |  ETA: 18s
#>  ■■■■■■■■■■■■■■■■■■■■              64% |  ETA: 14s
#>  ■■■■■■■■■■■■■■■■■■■■■■■           73% |  ETA: 11s
#>  ■■■■■■■■■■■■■■■■■■■■■■■■■■        82% |  ETA:  7s
#>  ■■■■■■■■■■■■■■■■■■■■■■■■■■■■      91% |  ETA:  4s
head(biv_kamp_lite_var)
#> # A tibble: 6 × 6
#>       r      k theo_csr kamp_csr      var  pvalue
#>   <dbl>  <dbl>    <dbl>    <dbl>    <dbl>   <dbl>
#> 1     0     0        0        0        0  NaN    
#> 2    10     0      314.     524.  366275.   0.807
#> 3    20  2104.    1257.    2138. 1523941.   0.511
#> 4    30  6365.    2827.    4609. 3399440.   0.170
#> 5    40  7795.    5027.    7830. 6014528.   0.506
#> 6    50 14284.    7854.   11862. 9554116.   0.217
biv_kamp_lite_var %>%
  ggplot(aes(x = r, y = var)) +
  geom_line() +
  geom_hline(yintercept = 0, linetype = "dashed", color = "blue") +
  labs(title = "Bivariate KAMP lite Variance", x = "r", y = "Variance") +
  theme_minimal()