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 exclusivity
2018
Analysis of mutation, selection, and epistasis: an informed approach to cancer clinical trials
Wilkins JF, Cannataro VL, Shuch B, Townsend JP. Analysis of mutation, selection, and epistasis: an informed approach to cancer clinical trials. Oncotarget 2018, 9: 22243-22253. PMID: 29854275, PMCID: PMC5976461, DOI: 10.18632/oncotarget.25155.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsStrength of selectionMutation rateSomatic variantsSynergistic epistasisAnalysis of mutationsDetailed mechanistic knowledgeGenetic architectureContribution of mutationsLineage selectionDrug development effortsEvolutionary principlesTherapeutic potentialDrug developmentMechanistic knowledgeEpistasisMutationsCancer typesVariant frequencyVariantsGenesSelectionClinical trialsPotential therapeutic benefitSubstantial clinical benefitRigorous guidance
2015
Gene Expression Evolves under a House-of-Cards Model of Stabilizing Selection
Hodgins-Davis A, Rice DP, Townsend JP. Gene Expression Evolves under a House-of-Cards Model of Stabilizing Selection. Molecular Biology And Evolution 2015, 32: 2130-2140. PMID: 25901014, PMCID: PMC4592357, DOI: 10.1093/molbev/msv094.Peer-Reviewed Original ResearchConceptsGene expression evolvesGene expressionPhenotypic evolutionGenetic architectureExpression evolvesEvolutionary quantitative genetic modelsMutation accumulation linesNatural genetic variationStrength of selectionGenomic mutation rateQuantitative genetic modelGenomic data setsGene expression levelsEffects of selectionEvolutionary timeRegulatory evolutionStabilizing selectionAccumulation linesGene regulationMost genesNatural selectionGenetic variationMutational effectsFruit flyPhenotype space
2004
Monitoring and modeling horizontal gene transfer
Nielsen KM, Townsend JP. Monitoring and modeling horizontal gene transfer. Nature Biotechnology 2004, 22: 1110-1114. PMID: 15340481, DOI: 10.1038/nbt1006.Peer-Reviewed Original ResearchConceptsHorizontal gene transfer eventsPopulation genetic approachesGene transfer eventsStrength of selectionHorizontal gene transferPopulation genetic modelsWild-type bacteriaLarge bacterial populationsHGT hypothesisBacterial generation timesHGT eventsTransgenic plantsGenetic approachesBacterial communitiesBacterial transformantsBacterial populationsPopulation sizeCurrent monitoring effortsGene transferTransfer eventsYears of growthGeneration timeGenetic modelsBacteriaTime of sampling