ArticleBioinformatics (Oxford, England)2016
A weighted exact test for mutually exclusive mutations in cancer.
Article in Bioinformatics (Oxford, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Variant-Specific Landscape of Mutual Exclusivity Among BRAF, EGFR, and KRAS Oncogenes Reveals Overlap With Functionally Antagonistic Mutant Pairs.International journal of cancer · 2026Article
- Empowering Inference of Epistasis on the Basis of Mutual Exclusivity, Co-Occurrence, Functional Antagonism and Synergy in ERK-Pathway Oncogenes.International journal of cancer · 2026Article
- Review
- A latent variable model for evaluating mutual exclusivity and co-occurrence between driver mutations in cancer.bioRxiv : the preprint server for biology · 2024Article
- Adaptation of a mutual exclusivity framework to identify driver mutations within oncogenic pathways.American journal of human genetics · 2024Article
- The genomic landscape of canine diffuse large B-cell lymphoma identifies distinct subtypes with clinical and therapeutic implications.Lab animal · 2022Article
- Concurrent TP53 Mutations Facilitate Resistance Evolution in EGFR-Mutant Lung Adenocarcinoma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2022Article
- Germline mutations in mitochondrial complex I reveal genetic and targetable vulnerability in IDH1-mutant acute myeloid leukaemia.Nature communications · 2022Article
- A computational approach for the discovery of significant cancer genes by weighted mutation and asymmetric spreading strength in networks.Scientific reports · 2021Article
- MEScan: a powerful statistical framework for genome-scale mutual exclusivity analysis of cancer mutations.Bioinformatics (Oxford, England) · 2021Article
- Analysis, identification and visualization of subgroups in genomics.Briefings in bioinformatics · 2021Review
- Genomic Alterations inCancer research · 2021Article
- A forward selection algorithm to identify mutually exclusive alterations in cancer studies.Journal of human genetics · 2021Article
- ORN: Inferring patient-specific dysregulation status of pathway modules in cancer with OR-gate Network.PLoS computational biology · 2021Article
- The origins and genetic interactions of KRAS mutations are allele- and tissue-specific.Nature communications · 2021Article
- Fast mutual exclusivity algorithm nominates potential synthetic lethal gene pairs through brute force matrix product computations.Computational and structural biotechnology journal · 2021Article
- A Network-Centric Framework for the Evaluation of Mutual Exclusivity Tests on Cancer Drivers.Frontiers in genetics · 2021Article
- Genome-wide methylation patterns predict clinical benefit of immunotherapy in lung cancer.Clinical epigenetics · 2020Article
- Identifying multi-hit carcinogenic gene combinations: Scaling up a weighted set cover algorithm using compressed binary matrix representation on a GPU.Scientific reports · 2020Article
- Genomic basis for RNA alterations in cancer.Nature · 2020Article
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Authors and funding
3 authors.
Funding
Abstract
motivationThe somatic mutations in the pathways that drive cancer development tend to be mutually exclusive across tumors, providing a signal for distinguishing driver mutations from a larger number of random passenger mutations. This mutual exclusivity signal can be confounded by high and highly variable mutation rates across a cohort of samples. Current statistical tests for exclusivity that incorporate both per-gene and per-sample mutational frequencies are computationally expensive and have limited precision.
resultsWe formulate a weighted exact test for assessing the significance of mutual exclusivity in an arbitrary number of mutational events. Our test conditions on the number of samples with a mutation as well as per-event, per-sample mutation probabilities. We provide a recursive formula to compute P-values for the weighted test exactly as well as a highly accurate and efficient saddlepoint approximation of the test. We use our test to approximate a commonly used permutation test for exclusivity that conditions on per-event, per-sample mutation frequencies. However, our test is more efficient and it recovers more significant results than the permutation test. We use our Weighted Exclusivity Test (WExT) software to analyze hundreds of colorectal and endometrial samples from The Cancer Genome Atlas, which are two cancer types that often have extremely high mutation rates. On both cancer types, the weighted test identifies sets of mutually exclusive mutations in cancer genes with fewer false positives than earlier approaches. AVAILABILITY AND IMPLEMENTATION: See http://compbio.cs.brown.edu/projects/wext for software. CONTACT: braphael@cs.brown.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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