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
2021
The somatic molecular evolution of cancer: Mutation, selection, and epistasis
Dasari K, Somarelli JA, Kumar S, Townsend JP. The somatic molecular evolution of cancer: Mutation, selection, and epistasis. Progress In Biophysics And Molecular Biology 2021, 165: 56-65. PMID: 34364910, PMCID: PMC8819680, DOI: 10.1016/j.pbiomolbio.2021.08.003.Peer-Reviewed Original ResearchConceptsCancer evolutionEpistatic interactionsNeutral mutation rateCancer progressionEvolution of neoplasmsSingle nucleotide variantsMolecular evolutionRate of fixationGenetic interactionsEvolutionary biologyPhylogenetic analysisCopy number aberrationsPhylogenetic relationsNeutral mutationsGenomic dataSelective pressureSynonymous mutationsMutation rateChromosomal instabilityPhenotypic changesLoss of heterozygosityFitness landscapeClonal deconvolutionTumor microenvironmentEnvironment interaction
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
2005
Concerted Evolution in the Repeats of an Immunomodulating Cell Surface Protein, SOWgp, of the Human Pathogenic Fungi Coccidioides immitis and C. posadasii
Johannesson H, Townsend JP, Hung CY, Cole GT, Taylor JW. Concerted Evolution in the Repeats of an Immunomodulating Cell Surface Protein, SOWgp, of the Human Pathogenic Fungi Coccidioides immitis and C. posadasii. Genetics 2005, 171: 109-117. PMID: 15965255, PMCID: PMC1456504, DOI: 10.1534/genetics.105.040923.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, FungalCoccidioidesCoccidioidomycosisDNA, FungalEvolution, MolecularGene ConversionGenetic VariationHumansMembrane GlycoproteinsMutationPhylogenyPolymorphism, GeneticRecombination, GeneticRepetitive Sequences, Nucleic AcidSequence Analysis, DNASpecies SpecificityTandem Repeat SequencesConceptsPathogenic fungus Coccidioides immitisConcerted evolutionProtein-coding genesC. posadasiiGenetic distance analysisPoint mutation rateHost-pathogen interactionsCell surface proteinsGenome dynamicsPathogen's benefitMultigene familyUnequal crossingGeographic rangeFungus Coccidioides immitisRepetitive domainEntire geneMutation rateRepetitive arraysSurface proteinsDistance analysisGenesHost immune systemImmune systemImmunodominant proteinsParasitic phase