Featured Publications
Cancer Relevance of Human Genes
Qing T, Mohsen H, Cannataro VL, Marczyk M, Rozenblit M, Foldi J, Murray M, Townsend J, Kluger Y, Gerstein M, Pusztai L. Cancer Relevance of Human Genes. Journal Of The National Cancer Institute 2022, 114: 988-995. PMID: 35417011, PMCID: PMC9275765, DOI: 10.1093/jnci/djac068.Peer-Reviewed Original ResearchConceptsCore cancer genesHuman genesFunctional importanceSomatic mutation frequencySelection pressureGene/protein networksCancer genesHigher somatic mutation frequencyNegative selection pressureGene-gene interaction networksMutation frequencyProtein-truncating variantsGenomic contextCell viabilityGenes decreasesCancer Genome AtlasInteraction networksProtein networkCancer relevanceCancer cell viabilityCell survivalGenesCancer biologyGenome AtlasSearch toolsMolecular Biology and Evolution of Cancer: From Discovery to Action
Somarelli JA, Gardner H, Cannataro VL, Gunady EF, Boddy AM, Johnson NA, Fisk J, Gaffney SG, Chuang JH, Li S, Ciccarelli FD, Panchenko AR, Megquier K, Kumar S, Dornburg A, DeGregori J, Townsend JP. Molecular Biology and Evolution of Cancer: From Discovery to Action. Molecular Biology And Evolution 2019, 37: 320-326. PMID: 31642480, PMCID: PMC6993850, DOI: 10.1093/molbev/msz242.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEvolutionary processesMolecular evolutionary processesEvolution of cancerCancer cell populationsEcological nichesNew therapeutic modesCancer evolutionEcological theoryMolecular biologyCancer biologyCancer progressionSuite of conceptsCell populationsBiologyNicheEvolutionCirculatory systemDeeper understandingDiscoveryCancerEstimation 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
2022
Placing human gene families into their evolutionary context
Dornburg A, Mallik R, Wang Z, Bernal M, Thompson B, Bruford E, Nebert D, Vasiliou V, Yohe L, Yoder J, Townsend J. Placing human gene families into their evolutionary context. Human Genomics 2022, 16: 56. PMID: 36369063, PMCID: PMC9652883, DOI: 10.1186/s40246-022-00429-5.Peer-Reviewed Original ResearchConceptsHuman gene familyGene familyHuman genomeEvolutionary contextGene family evolutionNon-model organismsFirst human genomeGenome biologyComparative genomicsFamily evolutionDistant speciesDraft sequenceGenomic studiesGene expressionGenome sequencingSequence complexityGenomeCancer biologyUnprecedented insightsNovel discoveriesCritical roleOrganismsBiologyComparative approachFamily
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
PhyloOncology: Understanding cancer through phylogenetic analysis
Somarelli JA, Ware KE, Kostadinov R, Robinson JM, Amri H, Abu-Asab M, Fourie N, Diogo R, Swofford D, Townsend JP. PhyloOncology: Understanding cancer through phylogenetic analysis. Biochimica Et Biophysica Acta (BBA) - Reviews On Cancer 2016, 1867: 101-108. PMID: 27810337, PMCID: PMC9583457, DOI: 10.1016/j.bbcan.2016.10.006.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAdaptation, PhysiologicalAlgorithmsAnimalsBiomarkers, TumorCell Transformation, NeoplasticEvolution, MolecularGene Expression Regulation, NeoplasticGenetic FitnessGenetic Predisposition to DiseaseGenomicsHeredityHumansModels, GeneticMutationNeoplasmsPedigreePhenotypePhylogenySignal TransductionSystems BiologyTime FactorsConceptsDr. Robert A. GatenbyGenome-scale dataSystems biology approachPowerful systems biology approachUse of phylogeneticsPhylogenetic analysisBiology approachPhylogenetic applicationsSubclonal evolutionCancer biologyCancer progressionSuite of algorithmsPhylogeneticsCancer data setsCancer samplesImproved therapeutic interventionRobust approachDecades of researchFundamental insightsNew toolBiologyDiverse fieldsGatenbyData setsTherapeutic interventionsEarly 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
2015
Inferring the Origin of Metastases from Cancer Phylogenies
Hong WS, Shpak M, Townsend JP. Inferring the Origin of Metastases from Cancer Phylogenies. Cancer Research 2015, 75: 4021-4025. PMID: 26260528, PMCID: PMC4833389, DOI: 10.1158/0008-5472.can-15-1889.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsComplete phylogenyEvolutionary historyPhylogeny-based testsFuture phylogenetic studiesMolecular evolutionary modelsMetastatic subclonesMonophyletic cladePhylogenetic reconstructionCancer lineagesPhylogenetic studiesNatural selectionPhylogenyCancer phylogeniesOrigin of metastasesCancer biologyMetastatic cascadeSubclonesTargeted sequencingEvolutionary modelsDriver mutationsUltra-deep sequencingSequencingRecent studiesMonophylyClade