Featured Publications
Pairwise and higher-order epistatic effects among somatic cancer mutations across oncogenesis
Alfaro-Murillo J, Townsend J. Pairwise and higher-order epistatic effects among somatic cancer mutations across oncogenesis. Mathematical Biosciences 2023, 366: 109091. PMID: 37996064, PMCID: PMC10847963, DOI: 10.1016/j.mbs.2023.109091.Peer-Reviewed Original ResearchStrength of selectionEpistatic effectsSelection coefficientsMutation rateHigher-order epistatic effectsLarge mutation ratesLarge selection coefficientsSomatic cancer mutationsUncontrolled cell growthSomatic evolutionMultiple somatic mutationsDriver genesCancer mutationsCancer research communityGenesSomatic genotypeCell growthOncogenesisMutationsSomatic mutationsEvolutionary modelsConsequent trajectoriesCancer genotypesPersonalized cancer therapyMutual exclusivityEstimation of neutral mutation rates and quantification of somatic variant selection using canceffectsizeR
Mandell J, Cannataro V, Townsend J. Estimation of neutral mutation rates and quantification of somatic variant selection using canceffectsizeR. Cancer Research 2022, 83: 500-505. PMID: 36469362, PMCID: PMC9929515, DOI: 10.1158/0008-5472.can-22-1508.Peer-Reviewed Original ResearchConceptsMutation rateEpistatic effectsSite-specific mutation ratesNeutral mutation rateNucleotide mutation ratePan-cancer datasetCancer cell survivalFunctional impact scoresCustom genomesPairwise epistasisSet of variantsHuman genomeR packageTranscriptomic dataSomatic variant dataModel of selectionSingle nucleotideCancer effectsCell survivalNucleotide mutationsCancer biologyVariant dataMutational signature analysisMutationsSomatic mutations
2020
Germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden
Qing T, Mohsen H, Marczyk M, Ye Y, O’Meara T, Zhao H, Townsend JP, Gerstein M, Hatzis C, Kluger Y, Pusztai L. Germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden. Nature Communications 2020, 11: 2438. PMID: 32415133, PMCID: PMC7228928, DOI: 10.1038/s41467-020-16293-7.Peer-Reviewed Original ResearchConceptsAge groupsGermline variantsSomatic mutationsLate-onset cancerEarly-onset cancersCancer hallmark genesSomatic mutation burdenMutation burdenMalignant transformationCancer genesYounger ageGermline alterationsCancerVariant burdenBurdenAverage numberHallmark genesAgeNegative correlationStrong negative correlationMutationsPatientsGroup
2018
Effect Sizes of Somatic Mutations in Cancer
Cannataro VL, Gaffney SG, Townsend JP. Effect Sizes of Somatic Mutations in Cancer. Journal Of The National Cancer Institute 2018, 110: 1171-1177. PMID: 30365005, PMCID: PMC6235682, DOI: 10.1093/jnci/djy168.Peer-Reviewed Original ResearchConceptsSelection intensityRecurrent single nucleotide variantsCancer cell lineagesSomatic variantsSingle nucleotide variantsSequence surveysSomatic tissuesReproductive advantageCancer genomesDevelopment of cancerCell lineagesSelective advantageEvolutionary processesDriver genesNucleotide variantsCancer biologyGenetic alterationsSomatic mutationsCancer cellsRelative importanceCancer growthGenesMutationsCancer typesVariants
2016
Early and multiple origins of metastatic lineages within primary tumors
Zhao ZM, Zhao B, Bai Y, Iamarino A, Gaffney SG, Schlessinger J, Lifton RP, Rimm DL, Townsend JP. Early and multiple origins of metastatic lineages within primary tumors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 2140-2145. PMID: 26858460, PMCID: PMC4776530, DOI: 10.1073/pnas.1525677113.Peer-Reviewed Original ResearchConceptsMetastatic lineagesGenetic changesEarly genetic divergenceMolecular evolutionary modelsSingle genetic changeDivergent lineagesTumor phylogeneticsDivergence timesAncestral stateGenetic divergenceCancer lineagesPhylogenetic analysisEvolutionary processesLineagesCancer evolutionMultiple originsDriver genesCancer biologyCancer progressionSomatic mutationsTumor developmentEvolutionary modelsDriver mutationsChronogramMutations