update tp53 status classification

analyses/molecular-subtyping-MB/05-subtype-mb-shh.R

@@ -237,7 +237,7 @@ expr_df <- as.data.frame(t(subset_expr)) %>%
  GLI2_TPM = max(GLI2_TPM),
  CCND2_TPM = max(CCND2_TPM),
  PTEN_TPM = min(PTEN_TPM),
- TP53_TPM = min(PTEN_TPM),
+ TP53_TPM = min(TP53_TPM),
  .groups = "drop") %>%
  mutate(MYCN_TPM_zscore = as.vector(scale(MYCN_TPM)),
  GLI2_TPM_zscore = as.vector(scale(GLI2_TPM)),
@@ -262,8 +262,9 @@ tp53_df <- read_tsv(tp53_alterations_file) %>%
  tp53_HGVSp_Short = HGVSp_Short,
  tp53_CNV_loss_evidence = CNV_loss_evidence,
  tp53_hotspot = hotspot,
- tp53_activating = activating) %>%
- dplyr::select(match_id, starts_with("tp53"))
+ tp53_activating = activating,
+ tp53_overlap_domain = overlap_domain) %>%
+ dplyr::select(match_id, cancer_predispositions, starts_with("tp53"))
 
 
 # Create subtypes df that:
@@ -351,7 +352,21 @@ final_subtypes <- mb_subtypes %>%
  TRUE ~ NA_character_
  )) %>%
  dplyr::mutate(tp53_status = case_when(
- !is.na(TP53_germline_plp) | tp53_hotspot > 0 | !is.na(tp53_SV_type) | !is.na(tp53_Fusions) | grepl("amplification", consensus_CN_MYCN) |grepl("amplification", consensus_CN_GLI2) ~ "TP53 altered",
+ # check for activating mutations
+ tp53_activating == 1 ~ "TP53 activation",
+ # Loss
+ # germline P/LP
+ !is.na(TP53_germline_plp) | 
+ # other hotspot mutation 
+ tp53_hotspot >= 1 | 
+ # SNV + (CNV|SV)
+ tp53_SNV_indel_counts >= 1 & (tp53_CNV_loss_counts >=1 | tp53_SV_counts >=1) |
+ # >1 SNV/indel
+ tp53_SNV_indel_counts > 1 |
+ # frameshift or nonsense variant overlaps functional domain
+ tp53_overlap_domain >=1 |
+ # LFS + SNV/indel/CNV/SV
+ grepl("Li-Fraumeni syndrome",cancer_predispositions) & (tp53_SNV_indel_counts >= 1 | tp53_CNV_loss_counts >= 1 | tp53_SV_counts >=1) ~ "TP53 loss",
  TRUE ~ "TP53 wildtype"
  )) %>%
  right_join(mb_shh) %>%