diff --git a/analyses/molecular-subtyping-MB/06-mb-shh-umap.Rmd b/analyses/molecular-subtyping-MB/06-mb-shh-umap.Rmd new file mode 100644 index 0000000000..6ceb7fcf6c --- /dev/null +++ b/analyses/molecular-subtyping-MB/06-mb-shh-umap.Rmd @@ -0,0 +1,373 @@ +--- +title: 'Create MB SHH methylation UMAP' +output: + html_document: + toc: TRUE +toc_float: TRUE +author: Ryan Corbett +date: "2024" +--- + +Load libraries and set directory paths + +```{r} +suppressPackageStartupMessages({ + library(tidyverse) + library(umap) + library(ggplot2) + library(devtools) + library(gdata) +}) + +root_dir <- rprojroot::find_root(rprojroot::has_dir(".git")) + +data_dir <- file.path(root_dir, "data") +analysis_dir <- file.path(root_dir, "analyses", "molecular-subtyping-MB") +results_dir <- file.path(analysis_dir, "results") +input_dir <- file.path(analysis_dir, "input") +plots_dir <- file.path(analysis_dir, "plot") +``` + +Set file paths + +```{r} +hist_file <- file.path(data_dir, "histologies.tsv") +methyl_file <- file.path(data_dir, "v14", "methyl-beta-values.rds") +mb_shh_file <- file.path(results_dir, "mb_shh_subtypes_w_molecular_data.tsv") +``` + +Wrangle data. We will remove sample IDs from `mb_shh_subtypes` for which a high confidence methylation call indicates a non-MB tumor (to be further pathologically reviewed). + +```{r get methyl ids} +hist <- read_tsv(hist_file) + +mb_shh_subtypes <- read_tsv(mb_shh_file) %>% + dplyr::filter(!sample_id %in% c("7316-1884", "7316-1676", + "7316-1666", "7316-3202")) +``` + +Filter hist for mb shh methyl samples, and append to subtype df + +```{r} +hist_mb_methyl <- hist %>% + dplyr::filter(pathology_diagnosis == "Medulloblastoma", + experimental_strategy == "Methylation") %>% + dplyr::rename(Kids_First_Biospecimen_ID_methyl = Kids_First_Biospecimen_ID) + +mb_shh_subtypes <- mb_shh_subtypes %>% + left_join(hist_mb_methyl %>% + dplyr::select(match_id, Kids_First_Biospecimen_ID_methyl)) %>% + dplyr::filter(!is.na(Kids_First_Biospecimen_ID_methyl)) %>% + distinct(match_id, Kids_First_Biospecimen_ID_methyl, .keep_all = TRUE) %>% + # redefine un-subtyped samples as "unk" + dplyr::mutate(molecular_subtype = case_when( + molecular_subtype == "MB, SHH" ~ "MB, SHH unk", + TRUE ~ molecular_subtype + )) %>% + dplyr::mutate(molecular_subtype = fct_relevel(molecular_subtype, + c("MB, SHH alpha", "MB, SHH beta", + "MB, SHH gamma", "MB, SHH delta", + "MB, SHH unk"))) +``` + +Get number of samples by MB SHH subtype + +```{r} +table(mb_shh_subtypes$SHH_subtype) +``` + +Load methylation data and filter for ids in `mb_shh_subtypes` + +```{r load methyl} +methyl <- readRDS(methyl_file) + +mb_methyl <- methyl[,colnames(methyl) %in% c("Probe_ID", hist_mb_methyl$Kids_First_Biospecimen_ID_methyl)] + +mb_methyl <- mb_methyl %>% + distinct(Probe_ID, .keep_all = TRUE) %>% + column_to_rownames("Probe_ID") +``` + +Identify 20k most variable probes among MB samples + +```{r} +mb_methyl_var <- apply(mb_methyl, 1, var, na.rm = TRUE) + +mb_var_probes <- names(sort(mb_methyl_var, decreasing = TRUE)[1:20000]) +``` + +Generate UMAP results + +```{r} +set.seed(2024) + +mb_umap_results <- umap::umap(t(mb_methyl[mb_var_probes, ])) +mb_umap_plot_df <- data.frame(mb_umap_results$layout) %>% + tibble::rownames_to_column("Kids_First_Biospecimen_ID_methyl") %>% + left_join(hist_mb_methyl) +``` + +Plot UMAP with molecular subtype and age range + +```{r} +mb_umap_plot_df %>% + ggplot(aes(x = X1, + y = X2, + color = molecular_subtype)) + + geom_point(alpha = 0.7) + + labs(color = "molecular subtype") + + theme_bw() + + xlab("UMAP1") + + ylab("UMAP2") + +ggsave(file.path(plots_dir, "umap_mb.pdf"), + width = 5.5, height = 3.5) +``` + +Identify 20k most variable probes among MB Group 3/4 samples + +```{r} +g34_samples <- hist_mb_methyl %>% + dplyr::filter(molecular_subtype %in% c("MB, Group3", "MB, Group4")) %>% + pull(Kids_First_Biospecimen_ID_methyl) + +mb_g34_methyl_var <- apply(mb_methyl[,colnames(mb_methyl) %in% g34_samples], 1, var, na.rm = TRUE) + +mb_g34_var_probes <- names(sort(mb_g34_methyl_var, decreasing = TRUE)[1:20000]) +``` + +Generate UMAP results + +```{r} +mb_g34_umap_results <- umap::umap(t(mb_methyl[mb_g34_var_probes, colnames(mb_methyl) %in% g34_samples])) +mb_g34_umap_plot_df <- data.frame(mb_g34_umap_results$layout) %>% + tibble::rownames_to_column("Kids_First_Biospecimen_ID_methyl") %>% + left_join(hist_mb_methyl) +``` + +Plot UMAP with molecular subtype and methylation subtype + +```{r} +mb_g34_umap_plot_df %>% + dplyr::filter(grepl("MB_G34", dkfz_v12_methylation_subclass)) %>% + ggplot(aes(x = X1, + y = X2, + color = dkfz_v12_methylation_subclass, + shape = molecular_subtype)) + + geom_point(alpha = 0.7) + + labs(color = "methylation subtype", + shape = "molecular subtype") + + theme_bw() + + xlab("UMAP1") + + ylab("UMAP2") + +ggsave(file.path(plots_dir, "umap_mb_group34.pdf"), + width = 5.5, height = 3.5) +``` + +Identify 20k most variable probes among MB SHH samples + +```{r} +mb_shh_methyl_var <- apply(mb_methyl[,colnames(mb_methyl) %in% mb_shh_subtypes$Kids_First_Biospecimen_ID_methyl], 1, var, na.rm = TRUE) + +mb_shh_var_probes <- names(sort(mb_shh_methyl_var, decreasing = TRUE)[1:20000]) +``` + +Generate UMAP df + +```{r} +mb_shh_umap_results <- umap::umap(t(mb_methyl[mb_shh_var_probes, colnames(mb_methyl) %in% mb_shh_subtypes$Kids_First_Biospecimen_ID_methyl])) +mb_shh_umap_plot_df <- data.frame(mb_shh_umap_results$layout) %>% + tibble::rownames_to_column("Kids_First_Biospecimen_ID_methyl") %>% + inner_join(mb_shh_subtypes) + +mb_shh_umap_plot_df <- mb_shh_umap_plot_df %>% + dplyr::mutate(age_range = case_when( + age_at_diagnosis_years < 5 ~ "[0,5)", + age_at_diagnosis_years < 10 ~ "[5,10)", + age_at_diagnosis_years < 15 ~ "[10,15)", + TRUE ~ ">=15" + )) %>% + dplyr::mutate(age_range = fct_relevel(age_range, + c("[0,5)", "[5,10)", + "[10,15)", ">=15"))) %>% + dplyr::mutate(consensus_CN_MYCN = case_when( + is.na(consensus_CN_MYCN) ~ "neutral", + TRUE ~ consensus_CN_MYCN + )) %>% + dplyr::mutate(consensus_CN_GLI2 = case_when( + is.na(consensus_CN_GLI2) ~ "neutral", + TRUE ~ consensus_CN_GLI2 + )) %>% + dplyr::mutate(consensus_CN_CCND2 = case_when( + is.na(consensus_CN_CCND2) ~ "neutral", + TRUE ~ consensus_CN_CCND2 + )) %>% + dplyr::mutate(consensus_CN_PTEN = case_when( + is.na(consensus_CN_PTEN) ~ "neutral", + TRUE ~ consensus_CN_PTEN + )) %>% + dplyr::mutate(classification_source = case_when( + classification_source == "Genomic/Expression" ~ "Molecular", + is.na(classification_source) ~ "Unavailable", + TRUE ~ classification_source + )) %>% + write_tsv(file.path(results_dir, "mb_shh_subtypes_w_molecular_umap_data.tsv")) +``` + +Plot UMAP with molecular subtype, classification source, and age range + +```{r} +mb_shh_umap_plot_df %>% + ggplot(aes(x = X1, + y = X2, + color = molecular_subtype, + size = age_range, + shape = classification_source)) + + geom_point(alpha = 0.7) + + labs(color = "molecular subtype", + size = "age range (years)", + shape = "classifcation source") + + theme_bw() + + xlab("UMAP1") + + ylab("UMAP2") + + # colors to match subtypes in Garcia-Lopez 2020 review + scale_color_manual(values = c("aquamarine3", "goldenrod2", + "royalblue1", "plum4", + "gray")) + + guides(color = guide_legend(order = 1), + shape = guide_legend(order = 2), + size = guide_legend(order = 3)) + +ggsave(file.path(plots_dir, "umap_mb_shh.pdf"), + width = 6.5, height = 4.5) +``` + +Plot UMAP with methylation subtype and methylation score + +```{r} +mb_shh_umap_plot_df %>% + dplyr::filter(grepl("MB", dkfz_v12_methylation_subclass_collapsed)) %>% + + ggplot(aes(x = X1, + y = X2, + color = dkfz_v12_methylation_subclass_collapsed, + alpha = dkfz_v12_methylation_subclass_score_mean)) + + geom_point(size = 3) + + labs(color = "methylation subtype", + alpha = "methylation subtype score") + + theme_bw() + + xlab("UMAP1") + + ylab("UMAP2") + + # colors to match subtypes in Garcia-Lopez 2020 review + scale_color_manual(values = c("goldenrod2", "royalblue1", + "aquamarine3", "plum4")) + +ggsave(file.path(plots_dir, "umap_mb_shh_methylation_subtype.pdf"), + width = 5.5, height = 3.5) +``` + +Plot UMAP with CN status for MYCN, GLI2, CCND2, and PTEN + +```{r} +umap_plot_cn_df <- mb_shh_umap_plot_df %>% + dplyr::select(molecular_subtype, X1, X2, + consensus_CN_MYCN, + consensus_CN_GLI2, + consensus_CN_CCND2, + consensus_CN_PTEN) %>% + dplyr::rename(MCYN = consensus_CN_MYCN, + GLI2 = consensus_CN_GLI2, + CCND2 = consensus_CN_CCND2, + PTEN = consensus_CN_PTEN) %>% + gather(key = "gene_name", value = "CN_status", + -molecular_subtype, -X1, -X2) + +umap_plot_cn_df %>% + ggplot(aes(x = X1, + y = X2, + color = molecular_subtype, + shape = CN_status)) + + geom_point(alpha = 0.7, size = 3) + + labs(color = "methylation subtype", + shape = "CN status") + + facet_wrap(~gene_name, nrow = 2) + + theme_bw() + + xlab("UMAP1") + + ylab("UMAP2") + + # colors to match subtypes in Garcia-Lopez 2020 review + scale_color_manual(values = c("aquamarine3", "goldenrod2", + "royalblue1", "plum4", + "gray")) + +ggsave(file.path(plots_dir, "umap_mb_shh_cn_status.pdf"), + width = 8, height = 5.5) +``` + +Plot UMAP with TP53 alteration status + +```{r} +mb_shh_umap_plot_df %>% + ggplot(aes(x = X1, + y = X2, + color = molecular_subtype, + shape = tp53_status)) + + geom_point(alpha = 0.7, size = 3) + + labs(color = "methylation subtype", + shape = "TP53 status") + + theme_bw() + + xlab("UMAP1") + + ylab("UMAP2") + + # colors to match subtypes in Garcia-Lopez 2020 review + scale_color_manual(values = c("aquamarine3", "goldenrod2", + "royalblue1", "plum4", + "gray")) + +ggsave(file.path(plots_dir, "umap_mb_shh_tp53_status.pdf"), + width = 5.5, height = 3.5) +``` + +Identify 20k most variable probes among MB WNT samples + +```{r} +wnt_samples <- hist_mb_methyl %>% + dplyr::filter(molecular_subtype %in% c("MB, WNT")) %>% + pull(Kids_First_Biospecimen_ID_methyl) + +mb_wnt_methyl_var <- apply(mb_methyl[,colnames(mb_methyl) %in% wnt_samples], 1, var, na.rm = TRUE) + +mb_wnt_var_probes <- names(sort(mb_wnt_methyl_var, decreasing = TRUE)[1:20000]) +``` + +Generate UMAP df + +```{r} +set.seed(2024) + +mb_wnt_umap_results <- umap::umap(t(mb_methyl[mb_wnt_var_probes, colnames(mb_methyl) %in% wnt_samples])) +mb_wnt_umap_plot_df <- data.frame(mb_wnt_umap_results$layout) %>% + tibble::rownames_to_column("Kids_First_Biospecimen_ID_methyl") %>% + left_join(hist_mb_methyl) + +``` + +Plot UMAP with methylation subtype + +```{r} +mb_wnt_umap_plot_df %>% + ggplot(aes(x = X1, + y = X2, + color = dkfz_v12_methylation_subclass)) + + geom_point(alpha = 0.7, size = 3) + + labs(color = "methylation subtype") + + theme_bw() + + xlab("UMAP1") + + ylab("UMAP2") + +ggsave(file.path(plots_dir, "umap_mb_wnt.pdf"), + width = 5.5, height = 3.5) +``` + +```{r} +sessionInfo() +``` \ No newline at end of file diff --git a/analyses/molecular-subtyping-MB/06-mb-shh-umap.html b/analyses/molecular-subtyping-MB/06-mb-shh-umap.html new file mode 100644 index 0000000000..ee3ea6e9d2 --- /dev/null +++ b/analyses/molecular-subtyping-MB/06-mb-shh-umap.html @@ -0,0 +1,835 @@ + + + + + + + + + + + + + + + +Create MB SHH methylation UMAP + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + +
+
+
+
+
+ +
+ + + + + + + +

Load libraries and set directory paths

+
suppressPackageStartupMessages({
+  library(tidyverse)
+  library(umap)
+  library(ggplot2)
+  library(devtools)
+  library(gdata)
+})
+
+root_dir <- rprojroot::find_root(rprojroot::has_dir(".git"))
+
+data_dir <- file.path(root_dir, "data")
+analysis_dir <- file.path(root_dir, "analyses", "molecular-subtyping-MB")
+results_dir <- file.path(analysis_dir, "results")
+input_dir <- file.path(analysis_dir, "input")
+plots_dir <- file.path(analysis_dir, "plot")
+

Set file paths

+
hist_file <- file.path(data_dir, "histologies.tsv")
+methyl_file <- file.path(data_dir, "v14", "methyl-beta-values.rds")
+mb_shh_file <- file.path(results_dir, "mb_shh_subtypes_w_molecular_data.tsv")
+

Wrangle data. We will remove sample IDs from +mb_shh_subtypes for which a high confidence methylation +call indicates a non-MB tumor (to be further pathologically +reviewed).

+
hist <- read_tsv(hist_file)
+
## Rows: 47895 Columns: 66
+## ── Column specification ────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
+## Delimiter: "\t"
+## chr (45): Kids_First_Participant_ID, Kids_First_Biospecimen_ID, sample_id, a...
+## dbl (21): cell_line_passage, OS_days, EFS_days, age_at_diagnosis_days, age_a...
+## 
+## ℹ Use `spec()` to retrieve the full column specification for this data.
+## ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
+
mb_shh_subtypes <- read_tsv(mb_shh_file) %>%
+  dplyr::filter(!sample_id %in% c("7316-1884", "7316-1676",
+                     "7316-1666", "7316-3202"))
+
## Rows: 265 Columns: 79
+## ── Column specification ────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
+## Delimiter: "\t"
+## chr (42): Kids_First_Participant_ID, Kids_First_Biospecimen_ID, match_id, mo...
+## dbl (33): age_at_diagnosis_years, dkfz_v12_methylation_subclass_score_mean, ...
+## lgl  (4): SMO_csq, TP53_csq, PTEN_exp_status, TP53_exp_status
+## 
+## ℹ Use `spec()` to retrieve the full column specification for this data.
+## ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
+

Filter hist for mb shh methyl samples, and append to subtype df

+
hist_mb_methyl <- hist %>%
+  dplyr::filter(pathology_diagnosis == "Medulloblastoma",
+                experimental_strategy == "Methylation") %>%
+  dplyr::rename(Kids_First_Biospecimen_ID_methyl = Kids_First_Biospecimen_ID)
+
+mb_shh_subtypes <- mb_shh_subtypes %>%
+  left_join(hist_mb_methyl %>%
+              dplyr::select(match_id, Kids_First_Biospecimen_ID_methyl)) %>%
+  dplyr::filter(!is.na(Kids_First_Biospecimen_ID_methyl)) %>%
+  distinct(match_id, Kids_First_Biospecimen_ID_methyl, .keep_all = TRUE) %>%
+  # redefine un-subtyped samples as "unk"
+  dplyr::mutate(molecular_subtype = case_when(
+    molecular_subtype == "MB, SHH" ~ "MB, SHH unk",
+    TRUE ~ molecular_subtype
+  )) %>%
+  dplyr::mutate(molecular_subtype = fct_relevel(molecular_subtype,
+                                               c("MB, SHH alpha", "MB, SHH beta",
+                                                 "MB, SHH gamma", "MB, SHH delta",
+                                                 "MB, SHH unk")))
+
## Joining with `by = join_by(match_id)`
+
## Warning in left_join(., hist_mb_methyl %>% dplyr::select(match_id, Kids_First_Biospecimen_ID_methyl)): Detected an unexpected many-to-many relationship between `x` and `y`.
+## ℹ Row 31 of `x` matches multiple rows in `y`.
+## ℹ Row 226 of `y` matches multiple rows in `x`.
+## ℹ If a many-to-many relationship is expected, set `relationship = "many-to-many"` to silence this warning.
+

Get number of samples by MB SHH subtype

+
table(mb_shh_subtypes$SHH_subtype)
+
## 
+## SHH_alpha  SHH_beta SHH_delta SHH_gamma 
+##         8        13        12        12
+

Load methylation data and filter for ids in +mb_shh_subtypes

+
methyl <- readRDS(methyl_file)
+
+mb_methyl <- methyl[,colnames(methyl) %in% c("Probe_ID", hist_mb_methyl$Kids_First_Biospecimen_ID_methyl)]
+
+mb_methyl <- mb_methyl %>%
+  distinct(Probe_ID, .keep_all = TRUE) %>%
+  column_to_rownames("Probe_ID")
+

Identify 20k most variable probes among MB samples

+
mb_methyl_var <- apply(mb_methyl, 1, var, na.rm = TRUE)
+
+mb_var_probes <- names(sort(mb_methyl_var, decreasing = TRUE)[1:20000])
+
set.seed(2024)
+
+mb_umap_results <- umap::umap(t(mb_methyl[mb_var_probes, ]))
+mb_umap_plot_df <- data.frame(mb_umap_results$layout) %>%
+  tibble::rownames_to_column("Kids_First_Biospecimen_ID_methyl") %>%
+  left_join(hist_mb_methyl)
+
## Joining with `by = join_by(Kids_First_Biospecimen_ID_methyl)`
+

Plot UMAP with molecular subtype and age range

+
mb_umap_plot_df %>%
+  ggplot(aes(x = X1, 
+             y = X2,
+             color = molecular_subtype)) +
+  geom_point(alpha = 0.7) +
+  labs(color = "molecular subtype") +
+  theme_bw() +
+  xlab("UMAP1") +
+  ylab("UMAP2") 
+

+
ggsave(file.path(plots_dir, "umap_mb.pdf"),
+       width = 5.5, height = 3.5)
+
mb_umap_plot_df <- mb_umap_plot_df %>%
+  dplyr::mutate(methyl_mismatch = case_when(
+    sample_id %in% c("7316-1884", "7316-1676",
+                     "7316-1666", "7316-3202") ~ "Yes",
+    TRUE ~ "No"
+  ))
+
+mb_umap_plot_df %>%
+  ggplot(aes(x = X1, 
+             y = X2,
+             color = molecular_subtype,
+             shape = methyl_mismatch)) +
+  geom_point(alpha = 0.7) +
+  labs(color = "molecular subtype",
+       shape = "Non-MB methylation") +
+  theme_bw() +
+  xlab("UMAP1") +
+  ylab("UMAP2") 
+

+
ggsave(file.path(plots_dir, "umap_mb_methylation_mismatch.pdf"),
+       width = 5.5, height = 3.5)
+

Identify 20k most variable probes among MB Group 3/4 samples

+
g34_samples <- hist_mb_methyl %>%
+  dplyr::filter(molecular_subtype %in% c("MB, Group3", "MB, Group4")) %>%
+  pull(Kids_First_Biospecimen_ID_methyl)
+
+mb_g34_methyl_var <- apply(mb_methyl[,colnames(mb_methyl) %in% g34_samples], 1, var, na.rm = TRUE)
+
+mb_g34_var_probes <- names(sort(mb_g34_methyl_var, decreasing = TRUE)[1:20000])
+
mb_g34_umap_results <- umap::umap(t(mb_methyl[mb_g34_var_probes, colnames(mb_methyl) %in% g34_samples]))
+mb_g34_umap_plot_df <- data.frame(mb_g34_umap_results$layout) %>%
+  tibble::rownames_to_column("Kids_First_Biospecimen_ID_methyl") %>%
+  left_join(hist_mb_methyl)
+
## Joining with `by = join_by(Kids_First_Biospecimen_ID_methyl)`
+

Plot UMAP with molecular subtype and age range

+
mb_g34_umap_plot_df %>%
+  dplyr::filter(grepl("MB_G34", dkfz_v12_methylation_subclass))  %>%
+  ggplot(aes(x = X1, 
+             y = X2,
+             color = dkfz_v12_methylation_subclass,
+             shape = molecular_subtype)) +
+  geom_point(alpha = 0.7) +
+  labs(color = "methylation subtype",
+       shape = "molecular subtype") +
+  theme_bw() +
+  xlab("UMAP1") +
+  ylab("UMAP2") 
+

+
ggsave(file.path(plots_dir, "umap_mb_group34.pdf"),
+       width = 5.5, height = 3.5)
+

Identify 10k most variable probes among MB SHH samples

+
mb_shh_methyl_var <- apply(mb_methyl[,colnames(mb_methyl) %in% mb_shh_subtypes$Kids_First_Biospecimen_ID_methyl], 1, var, na.rm = TRUE)
+
+mb_shh_var_probes <- names(sort(mb_shh_methyl_var, decreasing = TRUE)[1:20000])
+

Generate UMAP df

+
mb_shh_umap_results <- umap::umap(t(mb_methyl[mb_shh_var_probes, colnames(mb_methyl) %in% mb_shh_subtypes$Kids_First_Biospecimen_ID_methyl]))
+mb_shh_umap_plot_df <- data.frame(mb_shh_umap_results$layout) %>%
+  tibble::rownames_to_column("Kids_First_Biospecimen_ID_methyl") %>%
+  inner_join(mb_shh_subtypes)
+
## Joining with `by = join_by(Kids_First_Biospecimen_ID_methyl)`
+
mb_shh_umap_plot_df <- mb_shh_umap_plot_df %>%
+  dplyr::mutate(age_range = case_when(
+    age_at_diagnosis_years < 5 ~ "[0,5)",
+    age_at_diagnosis_years < 10 ~ "[5,10)",
+    age_at_diagnosis_years < 15 ~ "[10,15)",
+    TRUE ~ ">=15"
+  )) %>%
+  dplyr::mutate(age_range = fct_relevel(age_range,
+                                        c("[0,5)", "[5,10)",
+                                          "[10,15)", ">=15"))) %>%
+  dplyr::mutate(consensus_CN_MYCN = case_when(
+    is.na(consensus_CN_MYCN) ~ "neutral",
+    TRUE ~ consensus_CN_MYCN
+  )) %>%
+    dplyr::mutate(consensus_CN_GLI2 = case_when(
+    is.na(consensus_CN_GLI2) ~ "neutral",
+    TRUE ~ consensus_CN_GLI2
+  )) %>%
+    dplyr::mutate(consensus_CN_CCND2 = case_when(
+    is.na(consensus_CN_CCND2) ~ "neutral",
+    TRUE ~ consensus_CN_CCND2
+  )) %>%
+    dplyr::mutate(consensus_CN_PTEN = case_when(
+    is.na(consensus_CN_PTEN) ~ "neutral",
+    TRUE ~ consensus_CN_PTEN
+  )) %>%
+  dplyr::mutate(classification_source = case_when(
+    classification_source == "Genomic/Expression" ~ "Molecular",
+    is.na(classification_source) ~ "Unavailable",
+    TRUE ~ classification_source
+  )) %>%
+  write_tsv(file.path(results_dir, "mb_shh_subtypes_w_molecular_umap_data.tsv"))
+

Plot UMAP with molecular subtype, classification source, and age +range

+
mb_shh_umap_plot_df %>%
+  ggplot(aes(x = X1, 
+             y = X2,
+             color = molecular_subtype,
+             size = age_range,
+             shape = classification_source)) +
+  geom_point(alpha = 0.7) +
+  labs(color = "molecular subtype",
+       size = "age range (years)",
+       shape = "classifcation source") +
+  theme_bw() +
+  xlab("UMAP1") +
+  ylab("UMAP2") +
+  # colors to match subtypes in Garcia-Lopez 2020 review
+  scale_color_manual(values = c("aquamarine3", "goldenrod2", 
+                                "royalblue1", "plum4",
+                                "gray")) +
+  guides(color = guide_legend(order = 1),
+         shape  = guide_legend(order = 2),
+         size  = guide_legend(order = 3))
+
## Warning: Using size for a discrete variable is not advised.
+

+
ggsave(file.path(plots_dir, "umap_mb_shh.pdf"),
+       width = 6.5, height = 4.5)
+
## Warning: Using size for a discrete variable is not advised.
+

Plot UMAP with methylation subtype and methylation score

+
mb_shh_umap_plot_df %>%
+  dplyr::filter(grepl("MB", dkfz_v12_methylation_subclass_collapsed)) %>%
+  
+  ggplot(aes(x = X1, 
+             y = X2,
+             color = dkfz_v12_methylation_subclass_collapsed,
+             alpha = dkfz_v12_methylation_subclass_score_mean)) +
+  geom_point(size = 3) +
+  labs(color = "methylation subtype",
+       alpha = "methylation subtype score") +
+  theme_bw() +
+  xlab("UMAP1") +
+  ylab("UMAP2") +
+  # colors to match subtypes in Garcia-Lopez 2020 review
+  scale_color_manual(values = c("goldenrod2", "royalblue1",
+                                "aquamarine3", "plum4"))
+

+
ggsave(file.path(plots_dir, "umap_mb_shh_methylation_subtype.pdf"),
+       width = 5.5, height = 3.5)
+

Plot UMAP with CN status for MYCN, GLI2, CCND2, and PTEN

+
umap_plot_cn_df <- mb_shh_umap_plot_df %>%
+  dplyr::select(molecular_subtype, X1, X2,
+                consensus_CN_MYCN,
+                consensus_CN_GLI2,
+                consensus_CN_CCND2,
+                consensus_CN_PTEN) %>%
+  dplyr::rename(MCYN = consensus_CN_MYCN,
+                GLI2 = consensus_CN_GLI2,
+                CCND2 = consensus_CN_CCND2,
+                PTEN = consensus_CN_PTEN) %>%
+  gather(key = "gene_name", value = "CN_status",
+         -molecular_subtype, -X1, -X2)
+
+umap_plot_cn_df %>%
+  ggplot(aes(x = X1, 
+             y = X2,
+             color = molecular_subtype,
+             shape = CN_status)) +
+  geom_point(alpha = 0.7, size = 3) +
+  labs(color = "methylation subtype",
+       shape = "CN status") +
+  facet_wrap(~gene_name, nrow = 2) +
+  theme_bw() +
+  xlab("UMAP1") +
+  ylab("UMAP2") +
+  # colors to match subtypes in Garcia-Lopez 2020 review
+  scale_color_manual(values = c("aquamarine3", "goldenrod2", 
+                                "royalblue1", "plum4",
+                                "gray"))
+

+
ggsave(file.path(plots_dir, "umap_mb_shh_cn_status.pdf"),
+       width = 8, height = 5.5)
+

Plot UMAP with TP53 alteration status

+
mb_shh_umap_plot_df %>%
+  ggplot(aes(x = X1, 
+             y = X2,
+             color = molecular_subtype,
+             shape = tp53_status)) +
+  geom_point(alpha = 0.7, size = 3) +
+  labs(color = "methylation subtype",
+       shape = "TP53 status") +
+  theme_bw() +
+  xlab("UMAP1") +
+  ylab("UMAP2") +
+  # colors to match subtypes in Garcia-Lopez 2020 review
+  scale_color_manual(values = c("aquamarine3", "goldenrod2", 
+                                "royalblue1", "plum4",
+                                "gray"))
+

+
ggsave(file.path(plots_dir, "umap_mb_shh_tp53_status.pdf"),
+       width = 5.5, height = 3.5)
+

Identify 20k most variable probes among MB samples

+
wnt_samples <- hist_mb_methyl %>%
+  dplyr::filter(molecular_subtype %in% c("MB, WNT")) %>%
+  pull(Kids_First_Biospecimen_ID_methyl)
+
+mb_wnt_methyl_var <- apply(mb_methyl[,colnames(mb_methyl) %in% wnt_samples], 1, var, na.rm = TRUE)
+
+mb_wnt_var_probes <- names(sort(mb_wnt_methyl_var, decreasing = TRUE)[1:20000])
+
set.seed(2024)
+
+mb_wnt_umap_results <- umap::umap(t(mb_methyl[mb_wnt_var_probes, colnames(mb_methyl) %in% wnt_samples]))
+mb_wnt_umap_plot_df <- data.frame(mb_wnt_umap_results$layout) %>%
+  tibble::rownames_to_column("Kids_First_Biospecimen_ID_methyl") %>%
+  left_join(hist_mb_methyl)
+
## Joining with `by = join_by(Kids_First_Biospecimen_ID_methyl)`
+

Plot UMAP with molecular subtype and age range

+
mb_wnt_umap_plot_df %>%
+  ggplot(aes(x = X1, 
+             y = X2,
+             color = dkfz_v12_methylation_subclass)) +
+  geom_point(alpha = 0.7, size = 3) +
+  labs(color = "methylation subtype") +
+  theme_bw() +
+  xlab("UMAP1") +
+  ylab("UMAP2") 
+

+
ggsave(file.path(plots_dir, "umap_mb_wnt.pdf"),
+       width = 5.5, height = 3.5)
+ + + +
+
+ +
+ + + + + + + + + + + + + + + + diff --git a/analyses/molecular-subtyping-MB/plot/umap_mb.pdf b/analyses/molecular-subtyping-MB/plot/umap_mb.pdf new file mode 100644 index 0000000000..f059c44840 Binary files /dev/null and b/analyses/molecular-subtyping-MB/plot/umap_mb.pdf differ diff --git a/analyses/molecular-subtyping-MB/plot/umap_mb_group34.pdf b/analyses/molecular-subtyping-MB/plot/umap_mb_group34.pdf new file mode 100644 index 0000000000..32bd3fa6c8 Binary files /dev/null and b/analyses/molecular-subtyping-MB/plot/umap_mb_group34.pdf differ diff --git a/analyses/molecular-subtyping-MB/plot/umap_mb_shh.pdf b/analyses/molecular-subtyping-MB/plot/umap_mb_shh.pdf new file mode 100644 index 0000000000..02a93965ec Binary files /dev/null and b/analyses/molecular-subtyping-MB/plot/umap_mb_shh.pdf differ diff --git a/analyses/molecular-subtyping-MB/plot/umap_mb_shh_cn_status.pdf b/analyses/molecular-subtyping-MB/plot/umap_mb_shh_cn_status.pdf new file mode 100644 index 0000000000..29d087d906 Binary files /dev/null and b/analyses/molecular-subtyping-MB/plot/umap_mb_shh_cn_status.pdf differ diff --git a/analyses/molecular-subtyping-MB/plot/umap_mb_shh_methylation_subtype.pdf b/analyses/molecular-subtyping-MB/plot/umap_mb_shh_methylation_subtype.pdf new file mode 100644 index 0000000000..e8188e15f2 Binary files /dev/null and b/analyses/molecular-subtyping-MB/plot/umap_mb_shh_methylation_subtype.pdf differ diff --git a/analyses/molecular-subtyping-MB/plot/umap_mb_shh_tp53_status.pdf b/analyses/molecular-subtyping-MB/plot/umap_mb_shh_tp53_status.pdf new file mode 100644 index 0000000000..3474ddc708 Binary files /dev/null and b/analyses/molecular-subtyping-MB/plot/umap_mb_shh_tp53_status.pdf differ diff --git a/analyses/molecular-subtyping-MB/plot/umap_mb_wnt.pdf b/analyses/molecular-subtyping-MB/plot/umap_mb_wnt.pdf new file mode 100644 index 0000000000..b3431764c1 Binary files /dev/null and b/analyses/molecular-subtyping-MB/plot/umap_mb_wnt.pdf differ diff --git a/analyses/molecular-subtyping-MB/results/mb_shh_subtypes_w_molecular_umap_data.tsv b/analyses/molecular-subtyping-MB/results/mb_shh_subtypes_w_molecular_umap_data.tsv new file mode 100644 index 0000000000..4b60118390 --- /dev/null +++ b/analyses/molecular-subtyping-MB/results/mb_shh_subtypes_w_molecular_umap_data.tsv @@ -0,0 +1,60 @@ +Kids_First_Biospecimen_ID_methyl X1 X2 Kids_First_Participant_ID Kids_First_Biospecimen_ID match_id molecular_subtype molecular_subtype_methyl final_shh_subtype sample_id age_at_diagnosis_years dkfz_v12_methylation_subclass_collapsed dkfz_v12_methylation_subclass_score_mean SHH_subtype 2q_loss 2q_gain 2p_loss 2p_gain 9q_loss 9q_gain 9p_loss 9p_gain 10q_loss 10q_gain 14q_loss 14q_gain 17p_loss 17p_gain consensus_CN_MYCN consensus_CN_GLI2 consensus_CN_CCND2 consensus_CN_PTEN consensus_CN_PPM1D consensus_CN_MDM4 consensus_CN_TP53 CREBBP_csq DDX3X_csq KMT2D_csq PTCH1_csq SMO_csq SUFU_csq TERT_csq TP53_csq RNU1-2_csq RNU1-1_csq U1_mutation ELP1_germline_plp SUFU_germline_plp PTCH1_germline_plp TP53_germline_plp MYCN_TPM GLI2_TPM CCND2_TPM PTEN_TPM TP53_TPM MYCN_TPM_zscore GLI2_TPM_zscore CCND2_TPM_zscore PTEN_TPM_zscore TP53_TPM_zscore MYCN_exp_status GLI2_exp_status CCND2_exp_status PTEN_exp_status TP53_exp_status cancer_predispositions tp53_score tp53_SV_type tp53_SV_counts tp53_Fusions tp53_Fusion_counts tp53_cn_less_ploidy tp53_SNV_indel_counts tp53_CNV_loss_counts tp53_HGVSp_Short tp53_CNV_loss_evidence tp53_hotspot tp53_activating tp53_overlap_domain tp53_altered classification_source tp53_status age_range +BS_07YB4SN1 -0.7347681260428249 0.8079966094225873 PT_FWWRWTV2 BS_07YB4SN1 PT_FWWRWTV2_7316-2439_Solid Tissue_Initial CNS Tumor MB, SHH gamma MB, SHH SHH gamma 7316-2439 2.083504449007529 MB_SHH_2 0.879236880789835 SHH_gamma 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_1GB1R07D -0.9191083844703507 -0.12536730660936524 PT_FN4GEEFR BS_1GB1R07D PT_FN4GEEFR_7316-3010_Solid Tissue_Progressive MB, SHH delta MB, SHH SHH delta 7316-3010 10.888432580424366 MB_SHH_4 0.968156384021408 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA missense_variant,splice_region_variant NA frameshift_variant NA NA NA NA NA NA 0 NA NA NA NA 53.98 19.8 39.43 12.35 34.55 -0.28944322621321994 -0.05439518967360809 -0.3149902076512226 -0.6241689917263463 -0.10228834074281072 NA NA NA NA NA None documented 0.6753451234483276 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [10,15) +BS_1Y8941MS 0.9326101795649491 -2.597024829040514 PT_XA98HG1C BS_1Y8941MS PT_XA98HG1C_7316-931_Solid Tissue_Initial CNS Tumor MB, SHH alpha NA SHH alpha 7316-931 9.06776180698152 MB_SHH_3 0.480522307333631 NA 0 0 0 0 0 0 0 0 0 0 0 0 1 0 neutral neutral amplification neutral NA NA loss NA NA NA NA NA NA missense_variant NA NA NA 0 NA NA NA NA 49.09 12.64 606.42 17.85 3.6 -0.3169835016628462 -0.2555526386842508 1.6133087833767523 -0.4551234060835622 -0.9750000731860016 NA NA NA NA NA None documented 0.7369943604929275 NA NA NA NA NA 1 0 p.R213* NA 0 0 1 loss Molecular TP53 loss [5,10) +BS_8KX1Y9WX -1.1049570718232737 0.8298979926344292 PT_NTEKMKTX BS_8KX1Y9WX PT_NTEKMKTX_7316-1650_Solid Tissue_Initial CNS Tumor MB, SHH gamma MB, SHH SHH gamma 7316-1650 0.45722108145106094 MB_SHH_2 0.999178645943358 SHH_gamma 0 0 0 0 1 0 1 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA stop_gained NA 37.9 8.22 91.97 26.29 25.63 -0.38000511358131633 -0.379730840447804 -0.13630481815826895 -0.19571527102445352 -0.3538097835018822 NA NA NA NA NA Other inherited conditions NOS 0.6369937749426169 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_9Z5PWXZB 1.8843673695296985 -1.1140749062563857 PT_FN4GEEFR BS_9Z5PWXZB PT_FN4GEEFR_7316-729_Solid Tissue_Initial CNS Tumor MB, SHH delta MB, SHH SHH delta 7316-729 10.888432580424366 MB_SHH_4 0.970570442153716 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA missense_variant,splice_region_variant NA frameshift_variant;stop_gained,splice_region_variant;frameshift_variant NA NA NA NA NA NA 0 NA NA NA NA 37.42 16.69 57.94 17.88 27.78 -0.382708453502752 -0.14176944476063308 -0.25203880758432934 -0.4542013392527835 -0.2931852205050207 NA NA NA NA NA None documented 0.5851006724145965 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [10,15) +BS_9ZTH8XZA -2.7921952354934536 2.2436129966159233 PT_5JA1N2H4 BS_9ZTH8XZA PT_5JA1N2H4_7316-839_Solid Tissue_Deceased MB, SHH gamma NA SHH gamma 7316-839 4.895277207392197 MB_SHH_2 0.799879978506574 SHH_gamma NA NA NA NA NA NA NA NA NA NA NA NA NA NA neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 65.99 19.04 132.91 9.78 22.38 -0.22180340859563055 -0.07574709766915122 0.00292966691675054 -0.7031593835630655 -0.4454515647762075 NA NA NA NA NA None documented 0.579815338088175 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_CAQMF903 -0.4778610854789602 0.9678711723896805 PT_T93J9EGZ BS_3J4T2YYW PT_T93J9EGZ_7316-2196_Solid Tissue_Initial CNS Tumor MB, SHH gamma MB, SHH SHH gamma 7316-2196 0.8049281314168378 MB_SHH_2 0.999068753587284 SHH_gamma 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA frameshift_variant NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_D78QCZ0H -0.07576809850283084 0.21343547658344453 PT_1NZGDP3P BS_D78QCZ0H PT_1NZGDP3P_7316-1104_Solid Tissue_Initial CNS Tumor MB, SHH unk NA NA 7316-1104 2.414784394250513 MB_SHH_1 0.682775100649892 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 76.31 11.99 192.72 25.65 35.81 -0.16368160028476272 -0.2738141389435969 0.2063398904716337 -0.2153860300810684 -0.06675952707953368 NA NA NA NA NA None documented 0.5054617220116 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Unavailable TP53 wildtype [0,5) +BS_EZZZ4AQH 2.423625246651433 -1.5969954485146831 PT_9S6WMQ92 BS_EZZZ4AQH PT_9S6WMQ92_7316-278_Solid Tissue_Initial CNS Tumor MB, SHH alpha NA SHH alpha 7316-278 15.151266255989048 MB_SHH_3 0.748616895479363 SHH_alpha 0 0 0 0 0 0 0 0 0 0 0 0 0 1 neutral neutral neutral neutral NA NA loss NA NA NA frameshift_variant NA NA NA NA NA NA 0 NA NA NA NA 104.72 11.18 70.15 38 14.54 -0.00367766868478653 -0.29657077772832047 -0.21051332974441755 0.16419814858954696 -0.6665197386810418 NA NA NA NA NA None documented 0.701720120119439 NA NA NA NA yes 1 1 p.R175H 1 1 0 0 loss Methylation TP53 loss >=15 +BS_FZ2SY1NJ 1.0995271935120838 -2.45396830767627 PT_XA98HG1C BS_3T0YKFMJ_PHOS PT_XA98HG1C_7316-3023_Solid Tissue_Progressive MB, SHH alpha NA SHH alpha 7316-3023 9.06776180698152 MB_SHH_3 0.745700819242141 SHH_alpha 0 0 0 0 0 0 0 0 0 0 0 0 1 0 amplification neutral amplification loss NA NA loss NA NA NA missense_variant NA NA NA NA NA NA 0 NA NA NA NA 291.87 8.12 2334.01 9.29 3.54 1.0503433027666584 -0.382540302026165 7.488738780219766 -0.7182198084657864 -0.9766919214556814 NA NA CCND2 high NA NA None documented 0.7758981166823903 NA NA NA NA NA 1 0 p.R213* NA 0 0 1 loss Methylation TP53 loss [5,10) +BS_FZ3J46KM -3.274940723851957 2.9069679650249873 PT_H3WWDMW9 BS_FZ3J46KM PT_H3WWDMW9_7316-2118_Solid Tissue_Deceased MB, SHH beta MB, SHH SHH beta 7316-2118 0.6078028747433265 MB_SHH_1 0.95893023716325 SHH_beta NA NA NA NA NA NA NA NA NA NA NA NA NA NA neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 7.56 4.1 95.1 3.11 20.12 -0.550878724448732 -0.4954806574762745 -0.1256598758454988 -0.9081655756062238 -0.5091778496008154 NA NA NA NA NA None documented 0.730689368455683 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_HMWNCF3E -2.7587508451418437 2.778035120592192 PT_3VQEVNDD BS_9G7ETYHR PT_3VQEVNDD_7316-1680_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-1680 1.9767282683093772 MB_SHH_1 0.999094598764668 SHH_beta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA stop_gained;frameshift_variant NA NA NA NA NA NA NA 0 NA NA NA NA 35.21 17.38 45.7 11.45 14.81 -0.3951550810576957 -0.12238415986994272 -0.293666313625322 -0.6518309966497111 -0.6589064214674822 NA NA NA NA NA None documented 0.6334968007739475 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_HR5ZGJ2N -2.3368053813071796 3.005661119433521 PT_CQ7EGCMB BS_7XQRH69M PT_CQ7EGCMB_7316-3809_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-3809 2.0369609856262834 MB_SHH_1 0.997284295085942 SHH_beta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA frameshift_variant NA NA NA NA NA NA NA 0 NA DEL NA NA 22.97 16.91 73.14 18.13 14.47 -0.4640902490543063 -0.13558862928823906 -0.20034451903669143 -0.4465174489962933 -0.6684935616623349 NA NA NA NA NA None documented 0.5673741656281114 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_M1MPGKYJ -3.2065682157751394 2.1816734214732816 PT_HM2GMT2H BS_3F5PR9GS PT_HM2GMT2H_7316-6_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-6 1.6536618754277892 MB_SHH_1 0.986611250621102 SHH_beta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 57.89 16.49 86.57 27.38 26.81 -0.2674222697698582 -0.14738836791735502 -0.15466989435282455 -0.1622135095061563 -0.3205367675315117 NA NA NA NA NA None documented 0.7017092306726902 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_NBY54GNQ 1.7710170952679887 -2.2925541309138184 PT_S4A0R1PM BS_1S2BHJ8K PT_S4A0R1PM_7316-2699_Solid Tissue_Initial CNS Tumor MB, SHH delta MB, SHH SHH delta 7316-2699 20.88432580424367 MB_SHH_4 0.94547148218896 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral gain NA NA NA NA NA NA NA NA intron_variant,splice_donor_region_variant NA NA NA 0 NA NA NA NA 30.04 37.79 1.62 16.18 15.93 -0.424272304794826 0.4510269482735236 -0.4435797504134719 -0.5064517929969168 -0.6273252537667917 NA NA NA NA NA None documented 0.47250631742327814 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype >=15 +BS_Q1AHDMR6 -0.8860123854860524 0.814082272002593 PT_WWZ2Q14R BS_DVQYQSVW PT_WWZ2Q14R_7316-3138_Solid Tissue_Initial CNS Tumor MB, SHH gamma MB, SHH SHH gamma 7316-3138 0.837782340862423 MB_SHH_2 0.999123315489716 SHH_gamma 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA NA NA splice_acceptor_variant NA NA NA NA 0 NA stop_gained&splice_region_variant NA NA 8.57 4.28 33 15.39 7.3 -0.5451904466973776 -0.4904236266352248 -0.3368582520828879 -0.5307328862074258 -0.8706694298890773 NA NA NA NA NA Gorlin Syndrome (PTCH1, SUFU) 0.6850423604926275 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_Q400D66E 2.4729563587452708 -2.1256778622242534 PT_9S6WMQ92 BS_1CZPVCXR PT_9S6WMQ92_7316-333_Solid Tissue_Progressive MB, SHH alpha NA SHH alpha 7316-333 15.151266255989048 MB_SHH_3 0.714555105844752 SHH_alpha 0 1 0 1 0 1 0 1 0 0 0 0 0 0 gain gain neutral loss NA gain loss NA NA NA frameshift_variant NA NA NA NA NA NA 0 NA NA NA NA 224.2 46.57 94.68 33.8 62.67 0.6692286934259194 0.6976976748536134 -0.12708827066063083 0.03510879228051169 0.6906245483138139 NA NA NA NA NA None documented 0.8722682535960412 NA NA NA NA yes 1 1 p.R175H 1 1 0 0 loss Methylation TP53 loss >=15 +BS_Q7PP5YJN 1.869695320036226 -1.809016319249998 PT_YV2S3ES7 BS_BA6AZWB3 PT_YV2S3ES7_7316-182_Solid Tissue_Initial CNS Tumor MB, SHH delta NA SHH delta 7316-182 36.50376454483231 MB_SHH_2 0.650962061507135 NA 0 0 0 0 0 0 0 0 0 0 1 0 0 0 neutral neutral neutral neutral NA NA loss NA missense_variant NA splice_acceptor_variant NA NA NA NA NA NA 0 NA NA NA NA 23.44 14.61 13.7 25.28 16.03 -0.4614432287145672 -0.2002062455905405 -0.4024963947782439 -0.22675818766067385 -0.6245055066506586 NA NA NA NA NA None documented 0.625544054750575 NA NA NA NA yes 0 1 NA 1 0 0 0 loss Molecular TP53 wildtype >=15 +BS_RRMTKV48 -1.3278156195744915 0.04198906572542693 PT_CXT81GRM BS_3CG2N4PD PT_CXT81GRM_7316-1772_Solid Tissue_Deceased MB, SHH beta NA SHH beta 7316-1772 3.3429158110882957 NA NA NA 0 0 0 0 0 0 0 0 1 0 0 0 0 1 gain neutral neutral loss gain NA loss NA NA missense_variant NA NA NA NA NA NA NA 0 NA NA NA NA 0.15 0.14 9.79 6.82 2.37 -0.5926115344858958 -0.6067353359793674 -0.4157940703191166 -0.7941366441999094 -1.0096829627144386 NA NA NA NA NA None documented 0.688301092293539 NA NA NA NA yes 1 1 p.A138T 1 0 0 0 loss Molecular TP53 loss [0,5) +BS_RWHC2Y7G 0.054957594042361 -0.09333800933921177 PT_EGGY1XC0 BS_CSY11X7E PT_EGGY1XC0_7316-2865_Solid Tissue_Initial CNS Tumor MB, SHH gamma NA SHH gamma 7316-2865 4.03832991101985 MB_SHH_3 0.505203159022563 NA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA frameshift_variant,splice_region_variant NA NA NA NA NA NA 0 NA NA NA NA 58 19.57 99.08 22.44 35.92 -0.2668027543711958 -0.06085695130383825 -0.1121241345021041 -0.3140471809744024 -0.0636578052517873 NA NA NA NA NA None documented 0.4350958181001188 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Molecular TP53 wildtype [0,5) +BS_S2QR3V7R -2.343524565591453 2.4179237422489717 PT_NCDHZ8H8 BS_7C40TRCY PT_NCDHZ8H8_7316-2780_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-2780 4.145106091718001 MB_SHH_1 0.996259786813413 SHH_beta 0 1 0 1 0 0 0 0 0 0 0 0 0 0 gain gain neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA splice_acceptor_variant NA 46.22 15.17 50.97 14.24 9.05 -0.33314722160976395 -0.18447326075171927 -0.27574335963545016 -0.5660787813872805 -0.8213238553567482 NA NA NA NA NA None documented 0.6620983084168066 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_T1BECW62 -2.0419358862702572 2.7481290679703263 PT_GR8P8NY5 BS_14P16D79_PHOS PT_GR8P8NY5_7316-178_Solid Tissue_Initial CNS Tumor MB, SHH alpha NA SHH alpha 7316-178 3.381245722108145 MB_SHH_1 0.698825484853667 NA 0 0 0 0 1 0 1 0 0 0 0 0 0 0 amplification neutral neutral neutral NA NA NA NA NA NA frameshift_variant NA NA NA NA NA NA 0 NA NA NA NA 152.76 5.24 68.6 8.44 22.69 0.26688160178557097 -0.46345279548295987 -0.21578478680026225 -0.744345035337853 -0.4367103487161949 NA NA NA NA NA None documented 0.6457034027258275 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Molecular TP53 wildtype [0,5) +BS_TRDMP775 -2.6926244242445443 2.930286665581394 PT_PABK01H0 BS_185Q218S PT_PABK01H0_7316-1669_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-1669 2.945927446954141 MB_SHH_1 0.999150207918272 SHH_beta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA stop_gained,frameshift_variant NA NA NA NA NA NA 0 NA NA NA NA 33.1 8.43 54.53 13.37 22.67 -0.4070385127956734 -0.3738309711332461 -0.2636360131071876 -0.5928187194798665 -0.43727429813942154 NA NA NA NA NA None documented 0.7150554080199313 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_XB98DENV -3.158628386203774 3.101858663809015 PT_H3WWDMW9 BS_WH5HDE0A PT_H3WWDMW9_7316-737_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-737 0.6078028747433265 MB_SHH_1 0.999131794253794 SHH_beta NA NA NA NA NA NA NA NA NA NA NA NA NA NA neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 25.99 9.33 76.17 4.98 15.46 -0.44708173538194 -0.34854581692799774 -0.19003967072752417 -0.8506900764876771 -0.6405780652126173 NA NA NA NA NA None documented 0.612941662447604 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_XPV22DSD -3.4554437798254716 3.480253473349749 PT_0WMP712K BS_J1AB8PMA PT_0WMP712K_7316-922_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-922 1.3141683778234086 MB_SHH_1 0.973492336154679 SHH_beta 0 1 0 1 0 0 0 0 0 0 0 0 0 0 gain gain neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 54.4 14.88 102.87 20.31 32.22 -0.2870778037819637 -0.19262069932896597 -0.09923457176555488 -0.3795139259596989 -0.16798844854871164 NA NA NA NA NA None documented 0.6804866436479787 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_Y0CPEZ59 -0.459136477638697 0.6506428376924238 PT_STRDJQ01 BS_VPBMDMQX PT_STRDJQ01_7316-1038_Solid Tissue_Initial CNS Tumor MB, SHH gamma MB, SHH SHH gamma 7316-1038 1.3004791238877482 MB_SHH_2 0.99805492848436 SHH_gamma NA NA NA NA NA NA NA NA NA NA NA NA NA NA neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 42.57 13.54 50.12 11.67 23.46 -0.3537038689290147 -0.2302674844790025 -0.27863415866607466 -0.6450691732239997 -0.4149982959219702 NA NA NA NA NA None documented 0.638739087578901 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_9AZ2YW9W -0.39625437419851783 -0.003001247324849965 PT_DTQE1NRN BS_9AZ2YW9W PT_DTQE1NRN_7316-4865_Solid Tissue_Initial CNS Tumor MB, SHH gamma MB, SHH SHH gamma 7316-4865 6.8199863107460645 MB_SHH_2 0.809681722220806 SHH_gamma NA NA NA NA NA NA NA NA NA NA NA NA NA NA neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [5,10) +BS_KC9C1TP7 -0.3749488046883851 0.631940573519435 PT_W5PW7QVB BS_KC9C1TP7 PT_W5PW7QVB_7316-6361_Solid Tissue_Initial CNS Tumor MB, SHH gamma MB, SHH SHH gamma 7316-6361 1.839835728952772 MB_SHH_2 0.992926404876636 SHH_gamma NA NA NA NA NA NA NA NA NA NA NA NA NA NA neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_AAHD7HKE -0.07555475468435091 -0.6825387853492237 PT_7WYPEC3Q BS_AAHD7HKE PT_7WYPEC3Q_7316-5881_Solid Tissue_Progressive MB, SHH gamma MB, SHH SHH gamma 7316-5881 1.9712525667351128 MB_SHH_2 0.85921126925921 SHH_gamma 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral loss amplification NA loss NA NA NA NA NA NA NA NA NA NA 0 NA NA frameshift_variant NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Other inherited conditions NOS NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_NHDD620E 3.2875316727716957 -2.550533261643615 PT_DY2GNA83 BS_5S47QSET PT_DY2GNA83_7316-8419_Solid Tissue_Deceased MB, SHH delta MB, SHH SHH delta 7316-8419 18.67488021902806 MB_SHH_4 0.8071268799422935 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 gain neutral neutral neutral NA NA loss NA missense_variant stop_gained NA NA NA NA NA NA NA 0 NA NA NA NA 88.38 18.7 122.13 16.18 18.39 -0.09570386517699392 -0.08529926703557839 -0.03373246667164003 -0.5064517929969168 -0.5579594747099178 NA NA NA NA NA None documented 0.7549142304178995 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype >=15 +BS_YQ09RJ0G 3.178156955358306 -2.5803876208068743 PT_DY2GNA83 BS_5S47QSET PT_DY2GNA83_7316-8419_Solid Tissue_Deceased MB, SHH delta MB, SHH SHH delta 7316-8419 18.67488021902806 MB_SHH_4 0.8071268799422935 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 gain neutral neutral neutral NA NA loss NA missense_variant stop_gained NA NA NA NA NA NA NA 0 NA NA NA NA 88.38 18.7 122.13 16.18 18.39 -0.09570386517699392 -0.08529926703557839 -0.03373246667164003 -0.5064517929969168 -0.5579594747099178 NA NA NA NA NA None documented 0.7549142304178995 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype >=15 +BS_WJP330JF 3.5934408664850173 -2.635651392515193 PT_DY2GNA83 BS_5S47QSET PT_DY2GNA83_7316-8419_Solid Tissue_Deceased MB, SHH delta MB, SHH SHH delta 7316-8419 18.67488021902806 MB_SHH_4 0.8071268799422935 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 gain neutral neutral neutral NA NA loss NA missense_variant stop_gained NA NA NA NA NA NA NA 0 NA NA NA NA 88.38 18.7 122.13 16.18 18.39 -0.09570386517699392 -0.08529926703557839 -0.03373246667164003 -0.5064517929969168 -0.5579594747099178 NA NA NA NA NA None documented 0.7549142304178995 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype >=15 +BS_A46S5GG6 3.440187728007876 -2.667951615403279 PT_DY2GNA83 BS_5S47QSET PT_DY2GNA83_7316-8419_Solid Tissue_Deceased MB, SHH delta MB, SHH SHH delta 7316-8419 18.67488021902806 MB_SHH_4 0.8071268799422935 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 gain neutral neutral neutral NA NA loss NA missense_variant stop_gained NA NA NA NA NA NA NA 0 NA NA NA NA 88.38 18.7 122.13 16.18 18.39 -0.09570386517699392 -0.08529926703557839 -0.03373246667164003 -0.5064517929969168 -0.5579594747099178 NA NA NA NA NA None documented 0.7549142304178995 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype >=15 +BS_S26W7E5B -3.617208598251326 3.1199845629139675 PT_GFGHFJ3S BS_S26W7E5B PT_GFGHFJ3S_7316-4694_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-4694 0.3531827515400411 MB_SHH_1 0.934894223982845 SHH_beta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA splice_donor_variant NA NA NA NA NA NA 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_7J3TGDGX -2.8588210841350232 3.4899065240536684 PT_M39RC0Y1 BS_19Z0ERYF PT_M39RC0Y1_7316-4523_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-4523 0.6872005475701575 MB_SHH_1 0.999769332524683 SHH_beta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA frameshift_variant;missense_variant NA NA NA NA NA NA NA 0 NA splice_donor_variant NA NA 56.22 25.3 59.45 41.6 30.98 -0.2768276399131866 0.10012519713624318 -0.24690338812992585 0.27484616828300573 -0.2029533127887619 NA NA NA NA NA None documented 0.5220571444987683 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_VJF0JW0Y 0.3582520258522921 -0.4272878939893243 PT_7WYPEC3Q BS_D46WVFCP PT_7WYPEC3Q_7316-4529_Solid Tissue_Initial CNS Tumor MB, SHH gamma NA SHH gamma 7316-4529 1.9712525667351128 MB_SHH_2 0.689137328643069 NA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA loss NA NA NA NA NA NA NA NA NA NA 0 NA NA frameshift_variant NA 96.61 9.16 45.66 35.47 20.97 -0.04935284944071075 -0.3533219016112113 -0.2938023512267632 0.0864371791938662 -0.4852099991136841 NA NA NA NA NA Other inherited conditions NOS 0.5026113649811991 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Molecular TP53 wildtype [0,5) +BS_6YWZ165E -2.699219746054194 1.8769921477344238 PT_PHY9WJR1 BS_6YWZ165E PT_PHY9WJR1_7316-4283_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-4283 1.894592744695414 MB_SHH_1 0.982574656048589 SHH_beta 0 0 0 0 0 0 0 1 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA frameshift_variant NA 117.39 16.59 67.42 20.57 27.3 0.06767924132477697 -0.14457890633899403 -0.21979789604277625 -0.371522680092949 -0.3067200066624596 NA NA NA NA NA None documented 0.482505315673096 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_AB2YMESE 3.044082115636531 -2.120412194720581 PT_2WSNYKAC BS_AB2YMESE PT_2WSNYKAC_7316-5320_Solid Tissue_Initial CNS Tumor MB, SHH delta MB, SHH SHH delta 7316-5320 17.853524982888434 MB_SHH_4 0.95682746508053 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA missense_variant NA NA NA NA NA NA NA NA 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype >=15 +BS_HP7S6Y13 -2.5595259455972474 3.5447064307248177 PT_Q0N3AG4D BS_C0GQVFWA PT_Q0N3AG4D_7316-9804_Solid Tissue_Initial CNS Tumor MB, SHH gamma NA SHH gamma 7316-9804 1.486652977412731 MB_SHH_2 0.596721019133947 NA 0 0 0 0 1 0 0 1 0 0 1 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 107.85 11.15 49.23 75.54 43.29 0.01395036038624214 -0.29741361620182877 -0.2816609952981403 1.3180111095041138 0.14415755720722126 NA NA NA NA NA None documented 0.5937837214749853 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Molecular TP53 wildtype [0,5) +BS_PYTJAVWN -0.611103521144361 -0.4753185793021919 PT_2S6A3RV8 BS_C8RVHTVV PT_2S6A3RV8_7316-2711_Solid Tissue_Initial CNS Tumor MB, SHH unk NA NA 7316-2711 13.61533196440794 NA NA NA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 1.94 0.58 3.56 14.07 4.53 -0.5825303293622084 -0.5943737050345793 -0.43698192674357605 -0.5713038267616939 -0.9487764250059638 NA NA NA NA NA None documented 0.598394280113084 NA NA NA NA NA 1 0 p.R342* NA 0 0 1 loss Unavailable TP53 loss [10,15) +BS_CT0QDRYM 1.2751460428862433 -0.8737890993740225 PT_KNJDVV4K BS_CT0QDRYM PT_KNJDVV4K_7316-4681_Solid Tissue_Initial CNS Tumor MB, SHH alpha NA SHH alpha 7316-4681 10.00684462696783 MB_SHH_3 0.55067973377944 NA 0 0 0 0 0 0 0 1 0 0 0 0 0 0 neutral neutral neutral loss amplification NA loss NA NA NA frameshift_variant NA NA NA NA NA NA 0 splice_acceptor_variant NA NA NA 44.67 15.11 46.77 22.92 28.94 -0.34187675677273344 -0.18615893769873584 -0.2900273077867711 -0.2992941116819412 -0.2604761539578769 NA NA NA NA NA None documented 0.6251149512527668 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Molecular TP53 wildtype [10,15) +BS_63JEXTS8 3.235062791287846 -1.9499081519898243 PT_SBSXK3XB BS_63JEXTS8 PT_SBSXK3XB_7316-8430_Solid Tissue_Initial CNS Tumor MB, SHH delta MB, SHH SHH delta 7316-8430 25.232032854209447 MB_SHH_4 0.979042678116461 SHH_delta 0 0 0 0 1 0 1 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA stop_gained NA frameshift_variant NA NA NA NA NA non_coding_transcript_exon_variant 1 NA NA NA NA 73.28 20.39 37.74 29.13 77.14 -0.1807464335388257 -0.0378193663612786 -0.3207377963121113 -0.10842627771072498 1.098641956018272 NA NA NA NA NA None documented 0.5566821703278613 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype >=15 +BS_C7G3F912 -1.0057473529943919 1.3308531621707227 PT_S0XSZAF2 BS_C7G3F912 PT_S0XSZAF2_7316-8068_Solid Tissue_Initial CNS Tumor MB, SHH gamma MB, SHH SHH gamma 7316-8068 0.36413415468856947 MB_SHH_2 0.998910818515608 SHH_gamma NA NA NA NA NA NA NA NA NA NA NA NA NA NA neutral neutral neutral neutral NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_336M1VHM 1.084886928263379 -1.351828883716159 PT_H9QTP1JF BS_336M1VHM PT_H9QTP1JF_7316-3334_Solid Tissue_Recurrence MB, SHH alpha MB, SHH SHH alpha 7316-3334 5.06776180698152 MB_SHH_3 0.881702842801557 SHH_alpha 0 0 0 0 1 0 0 1 0 0 0 0 0 0 neutral neutral neutral neutral NA gain NA NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [5,10) +BS_ABMPSB4H -3.583829142542 3.3464660828415607 PT_J6CREPMB BS_6W0VHGQE PT_J6CREPMB_7316-6528_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-6528 0.9801505817932924 MB_SHH_1 0.998880050882945 SHH_beta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral loss NA NA NA NA NA stop_gained frameshift_variant NA NA NA NA NA NA 0 NA NA NA NA 45.84 7.85 51.62 17.15 26.5 -0.3352873657142339 -0.3901258482877395 -0.2735327486120314 -0.47663829880173486 -0.32927798359152427 NA NA NA NA NA None documented 0.4692223175124489 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_DSXA9WZK 1.7279848268469893 -0.7534942475606237 PT_6H0WGQ6E BS_91NSXESW PT_6H0WGQ6E_7316-7503_Solid Tissue_Initial CNS Tumor MB, SHH alpha MB, SHH SHH alpha 7316-7503 7.383983572895278 MB_SHH_3 0.914490804936151 SHH_alpha 0 1 0 1 0 0 0 1 0 0 0 0 0 0 gain gain neutral neutral amplification gain NA NA NA NA NA NA NA NA NA NA NA 0 frameshift_variant NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [5,10) +BS_P14GK1PS 1.365537464090183 -2.4421277915064765 PT_W4M7YD0J BS_P14GK1PS PT_W4M7YD0J_7316-7598_Solid Tissue_Initial CNS Tumor MB, SHH alpha NA SHH alpha 7316-7598 11.38672142368241 MB_SHH_3 0.517898480548091 NA 0 0 0 0 0 0 0 0 0 0 0 0 1 0 amplification neutral neutral loss loss NA loss NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 87.57 4.64 37.01 49.77 38.63 -0.1002657512944167 -0.48030956495312543 -0.3232204825384124 0.5259557018651051 0.01275734159541942 NA NA NA NA NA None documented 0.8443400735613433 NA NA NA NA yes 1 1 p.R175H 1 1 0 0 loss Molecular TP53 loss [10,15) +BS_FM94M3PS 1.291683842279859 -1.4946552704510976 PT_RM8V31DA BS_1DMAMKFZ PT_RM8V31DA_7316-5539_Solid Tissue_Initial CNS Tumor MB, SHH alpha NA SHH alpha 7316-5539 9.270362765229295 MB_SHH_4 0.498608258755839 NA 0 0 0 0 0 1 0 1 0 0 0 0 0 0 neutral neutral neutral neutral NA NA loss NA NA NA NA NA NA NA NA NA NA 0 frameshift_variant NA NA NA 190.35 27.02 154.6 54.19 42.67 0.4785869093830052 0.14844793628405115 0.07669605629821544 0.6618068815998515 0.12667512508719617 NA NA NA NA NA None documented 0.5581852083525883 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Molecular TP53 wildtype [5,10) +BS_NK7H671N 1.2875397235292851 -1.7467816725100545 PT_VW5Y6N97 BS_DPRBAXTR PT_VW5Y6N97_7316-5515_Solid Tissue_Initial CNS Tumor MB, SHH alpha MB, SHH SHH alpha 7316-5515 14.557152635181383 MB_SHH_3 0.971707862308703 SHH_alpha 0 0 0 0 0 1 0 1 0 0 0 0 0 0 gain neutral neutral neutral NA gain NA NA stop_gained NA NA NA NA NA NA NA NA 0 frameshift_variant NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [10,15) +BS_PR38DGDZ -0.7888292979501621 -0.0872226612637177 PT_6XT5HH0S BS_3RGJ4VP1 PT_6XT5HH0S_7316-9450_Solid Tissue_Initial CNS Tumor MB, SHH gamma NA SHH gamma 7316-9450 3.7399041752224504 MB_SHH_2 0.781471535154154 SHH_gamma 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA missense_variant;missense_variant;missense_variant;missense_variant:missense_variant;missense_variant;missense_variant;missense_variant;missense_variant;missense_variant stop_gained missense_variant;splice_acceptor_variant;missense_variant missense_variant;stop_gained;splice_acceptor_variant:missense_variant;stop_gained;missense_variant;missense_variant;stop_gained;splice_acceptor_variant;missense_variant NA frameshift_variant:frameshift_variant;missense_variant missense_variant;missense_variant;missense_variant NA NA NA 0 NA NA NA NA 62.03 7.35 126.52 28.08 88.47 -0.24410596294747516 -0.4041731561795442 -0.01880233991347355 -0.1406986167879838 1.4181193042761506 NA NA NA NA NA None documented 0.6376484489366663 NA NA NA NA NA 3 0 p.R273C, p.Y236C, p.R158H NA 1 1 0 activated Methylation TP53 activation [0,5) +BS_CZNXC2S4 2.239458478884 -1.8398240205393506 PT_PTTBTPS6 BS_B5V3KSQY PT_PTTBTPS6_7316-9028_Solid Tissue_Recurrence MB, SHH alpha NA SHH alpha 7316-9028 8.952772073921972 MB_SHH_4 0.560980494148111 NA 0 0 0 0 1 0 1 0 0 0 0 0 0 0 loss amplification neutral loss NA NA loss NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 96.02 188.26 67.05 22.3 65.91 -0.05267570476080883 4.6784237852332184 -0.2210562438561069 -0.31835015951803686 0.7819843548765258 NA GLI2 high NA NA NA None documented 0.813935180703918 NA NA NA NA yes 1 1 p.R248W 1 1 1 0 activated Molecular TP53 activation [5,10) +BS_V8M4STE2 -0.5285163864458835 1.2951872556797146 PT_QF2ZH1V5 BS_EQKYB3JB PT_QF2ZH1V5_7316-680_Solid Tissue_Initial CNS Tumor MB, SHH gamma MB, SHH SHH gamma 7316-680 0.7994524298425736 MB_SHH_2 0.999158003626786 SHH_gamma 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral loss NA NA NA NA NA NA NA NA NA NA NA NA NA 0 NA splice_acceptor_variant NA NA 27.16 4.35 63.32 10.41 30.12 -0.4404923443234404 -0.4884570035303722 -0.23374175019049437 -0.6837959801167103 -0.2272031379875065 NA NA NA NA NA None documented 0.620174237944931 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_A83P2345 2.8121352165447213 -1.8806603142389309 PT_2N647SBA BS_A83P2345 PT_2N647SBA_7316-6685_Solid Tissue_Initial CNS Tumor MB, SHH delta MB, SHH SHH delta 7316-6685 20.71457905544148 MB_SHH_4 0.98961040786072 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA NA NA stop_gained,splice_region_variant NA NA NA NA NA NA 0 NA NA NA NA 67.35 14.41 39.68 38.71 53.95 -0.21414394548489607 -0.20582516874726237 -0.3141399726422154 0.18602039691797911 0.4447425997870086 NA NA NA NA NA None documented 0.5234109462974219 NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype >=15 +BS_SDV5CN6V -2.5367666529657726 3.2409489687004394 PT_M26VF62B BS_B1YQHE16 PT_M26VF62B_7316-3124_Solid Tissue_Initial CNS Tumor MB, SHH beta MB, SHH SHH beta 7316-3124 2.00684462696783 MB_SHH_1 0.966530581485858 SHH_beta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 gain neutral neutral loss NA NA NA NA NA NA stop_gained,frameshift_variant NA NA NA NA NA NA 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype [0,5) +BS_4VD4ZEQQ 2.9333472976633344 -2.293528903381066 PT_9KRSSPSF BS_4VD4ZEQQ PT_9KRSSPSF_7316-520_Solid Tissue_Initial CNS Tumor MB, SHH delta MB, SHH SHH delta 7316-520 22.458590006844627 MB_SHH_4 0.928933850371562 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA NA NA missense_variant NA stop_gained NA NA NA NA NA NA 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA None documented NA NA NA NA NA NA 0 0 NA NA 0 0 0 Other Methylation TP53 wildtype >=15 +BS_ZDJB4BK4 1.7691568478083992 -2.8534780543156693 PT_97EQQMT9 BS_397XFJY9 PT_97EQQMT9_7316-3114_Solid Tissue_Initial CNS Tumor MB, SHH alpha NA SHH alpha 7316-3114 11.759069130732374 MB_SHH_4 0.660800126438475 NA 0 0 0 0 0 0 0 0 1 0 0 0 1 0 neutral gain amplification loss loss NA loss NA NA NA NA NA NA NA NA NA non_coding_transcript_exon_variant 1 NA NA NA NA 33.04 5.57 82.88 6.22 31.8 -0.40737643028585285 -0.4541815722743688 -0.16721936308577084 -0.8125779808154858 -0.17983138643647056 NA NA NA NA NA None documented 0.8587780780259405 NA NA NA NA yes 1 1 p.R175H 1 1 0 0 loss Molecular TP53 loss [10,15) +BS_TVTTHYXP 2.0161363668523524 -1.346884234982041 PT_C9F2B4QF BS_JMMPW4G3 PT_C9F2B4QF_7316-4270_Solid Tissue_Initial CNS Tumor MB, SHH delta MB, SHH SHH delta 7316-4270 13.431895961670088 MB_SHH_4 0.992079901791254 SHH_delta 0 0 0 0 0 0 0 0 0 0 0 0 0 0 neutral neutral neutral neutral NA NA loss NA NA NA intron_variant,splice_donor_region_variant NA NA NA NA NA NA 0 NA NA NA NA 84.97 22.99 23.69 25.15 29.52 -0.11490884253552676 0.03522663467610558 -0.3685210038183161 -0.2307538105940488 -0.24412162068430504 NA NA NA NA NA None documented 0.610349716451152 NA NA NA NA yes 0 1 NA 1 0 0 0 loss Methylation TP53 wildtype [10,15) +BS_Z5QBHB6Z 1.7202096880581799 -2.6388783215723866 PT_V0C2E99Z BS_CN0GW92K PT_V0C2E99Z_7316-6991_Solid Tissue_Initial CNS Tumor MB, SHH alpha MB, SHH SHH alpha 7316-6991 6.882956878850103 MB_SHH_3 0.8342129803541252 SHH_alpha 0 0 0 0 0 0 0 0 0 0 0 0 0 0 amplification gain gain neutral NA NA loss NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 429.18 11.28 69.17 15.97 6.28 1.823667479042362 -0.29376131614995954 -0.21384625097972584 -0.5129062608123686 -0.8994308504736348 NA NA NA NA NA None documented 0.6841839824754014 NA NA NA NA yes 0 1 NA 1 0 0 0 loss Methylation TP53 wildtype [5,10) +BS_PRKJWXS8 1.514477117917667 -2.0931420326076378 PT_WF4Q4SF2 BS_3RAM3K7B PT_WF4Q4SF2_7316-8860_Solid Tissue_Initial CNS Tumor MB, SHH alpha MB, SHH SHH alpha 7316-8860 18.351813826146476 MB_SHH_3 0.932424020621748 SHH_alpha 0 0 0 0 1 0 0 1 0 0 0 0 0 0 neutral neutral amplification loss NA NA loss NA NA NA NA NA NA NA NA NA NA 0 NA NA NA NA 121.97 28.54 175.65 20.55 1.09 0.09347360974180938 0.19115175227513737 0.14828584405662193 -0.3721373913134682 -1.045775725800942 NA NA NA NA NA None documented 0.7742678447610065 DEL 1 TP53--FXR2 1 yes 0 1 NA 1 0 0 0 loss Methylation TP53 wildtype >=15