InVEx (Integrated Variant Explorer)

Overview

InVEx (Integrated Variant Explorer) is a statistical framework for identifying significantly mutated genes in cancer exome sequencing studies. It evaluates the enrichment of non-synonymous mutations relative to synonymous mutations within individual genes, accounting for gene-specific background mutation rates and trinucleotide context. InVEx complements MutSig by using an within-gene ratio-based test, making it particularly effective for detecting genes under positive selection in cancer cohorts.

Used by

  • Used together with MutSig in the TCGA GBM 2013 study to identify 71 significantly mutated genes from 291 exomes; jointly identified established drivers (PTEN, TP53, EGFR, PIK3CA, PIK3R1, NF1, RB1, IDH1, PDGFRA) and the novel GBM driver LZTR1 (mutated in 10 samples; hemizygous deletion at 22q in 5/6 with copy number data) PMID:24120142
  • InVEx (Bonferroni p < 0.05 or Q < 0.1) used alongside MutSig to identify 13 significantly mutated genes in 318 melanoma WES cases, including RAC1 UV hot-spot (6.9%) and NF1 loss-of-function enrichment (LoF p = 1.8eā€“11). PMID:26091043

Notes

  • InVEx evaluates non-synonymous to synonymous mutation ratios within genes, complementing the MutSig approach which uses a background mutation rate model.
  • The combined use of MutSig and InVEx increases sensitivity for detecting genes under selection with diverse mutation profiles.
  • InVEx was developed at the Broad Institute as part of the TCGA GBM analysis pipeline.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26091043

This page was processed by crosslinker on 2026-05-14.