Featured Publications
Attribution of Cancer Origins to Endogenous, Exogenous, and Preventable Mutational Processes
Cannataro VL, Mandell JD, Townsend JP. Attribution of Cancer Origins to Endogenous, Exogenous, and Preventable Mutational Processes. Molecular Biology And Evolution 2022, 39: msac084. PMID: 35580068, PMCID: PMC9113445, DOI: 10.1093/molbev/msac084.Peer-Reviewed Original ResearchConceptsBurden of cancerPublic health strategiesWhole-exome sequencingTobacco exposureLung cancerProstate adenocarcinomaBreast cancerCancer effectsHealth strategiesOncogenic driversCancer originCancer typesCancer cell lineagesCancerPathogen exposureExogenous mutational processesMajority of mutationsTumorsSingle nucleotide variantsPreventable processActivity accountsSurvivalOncogenic variantsCell lineagesProliferationInfection with alternate frequencies of SARS-CoV-2 vaccine boosting for patients undergoing antineoplastic cancer treatments
Townsend J, Hassler H, Emu B, Dornburg A. Infection with alternate frequencies of SARS-CoV-2 vaccine boosting for patients undergoing antineoplastic cancer treatments. Journal Of The National Cancer Institute 2023, 115: 1626-1628. PMID: 37599438, PMCID: PMC10699797, DOI: 10.1093/jnci/djad158.Peer-Reviewed Original ResearchConceptsReinfection riskAntineoplastic therapyAntibody dataSARS-CoV-2 infectionSARS-CoV-2 vaccinesChemotherapy-immunotherapy combinationsPfizer-BioNTech BNT162b2COVID-19 vaccinationHigh infection riskFrequent boostingRituximab therapyBreakthrough infectionsVaccination scheduleAntibody levelsBooster scheduleVaccination frequencyImmune responseAdditional interventionsReduced riskHigh riskHormonal treatmentGeneral populationNecessitating assessmentPatientsInfection riskCancer 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 understandingDiscoveryCancer
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 interactionIdentifying modules of cooperating cancer drivers
Klein MI, Cannataro VL, Townsend JP, Newman S, Stern DF, Zhao H. Identifying modules of cooperating cancer drivers. Molecular Systems Biology 2021, 17: msb20209810. PMID: 33769711, PMCID: PMC7995435, DOI: 10.15252/msb.20209810.Peer-Reviewed Original ResearchConceptsCancer typesNRAS-mutant melanomaCombination of alterationsMultiple cancer typesClinical outcomesNFE2L2 mutationsIndividual patientsDriver alterationsEffective personalized treatmentPathway inhibitionTherapeutic potentialCancer etiologyPersonalized treatmentTumor formationTCGA cancer typesAlterationsPatientsCancer driversEtiologyMelanomaCancer
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 typesVariantsNeutral Theory and the Somatic Evolution of Cancer
Cannataro VL, Townsend JP. Neutral Theory and the Somatic Evolution of Cancer. Molecular Biology And Evolution 2018, 35: 1308-1315. PMID: 29684198, PMCID: PMC5967571, DOI: 10.1093/molbev/msy079.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, BiologicalAnimalsEvolution, MolecularGenetic DriftHumansNeoplasmsSelection, GeneticHeterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C
Cannataro VL, Gaffney SG, Stender C, Zhao ZM, Philips M, Greenstein AE, Townsend JP. Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C. Oncogene 2018, 37: 2444-2455. PMID: 29453361, DOI: 10.1038/s41388-017-0105-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SubstitutionAnimalsCase-Control StudiesDisease ProgressionDrug Resistance, NeoplasmFemaleGenetic HeterogeneityHigh-Throughput Nucleotide SequencingHumansMaleMiceMice, Inbred BALB CMice, NudeNeoplasmsOncogenesPoint MutationPolymorphism, Single NucleotideProto-Oncogene Proteins p21(ras)Sequence Analysis, DNAYoung AdultConceptsTime of treatmentTargeted therapyLung tumorsDe novo mutationsNew targeted therapiesPatient-derived xenograftsHighest fitness advantageKRAS G12C variantNovo mutationsEvidence of heterogeneityNovel KRAS mutationPreclinical promiseSuch therapyHigh prevalenceKRAS mutationsTreatment resistanceBRAF V600EKRASTherapyTargeted inhibitorsTumorsAssociated oncogeneRAS genesHuman cancersOncogenic mutationsSomatic evolutionary timings of driver mutations
Gomez K, Miura S, Huuki LA, Spell BS, Townsend JP, Kumar S. Somatic evolutionary timings of driver mutations. BMC Cancer 2018, 18: 85. PMID: 29347918, PMCID: PMC5774140, DOI: 10.1186/s12885-017-3977-y.Peer-Reviewed Original Research
2017
Radiation-Specific Clinical Data Should Be Included in Existing Large-Scale Genomic Datasets
Chen WS, Townsend JP, Yu JB. Radiation-Specific Clinical Data Should Be Included in Existing Large-Scale Genomic Datasets. International Journal Of Radiation Oncology • Biology • Physics 2017, 98: 8-10. PMID: 28587055, DOI: 10.1016/j.ijrobp.2017.01.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
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 interventionsPathScore: a web tool for identifying altered pathways in cancer data
Gaffney SG, Townsend JP. PathScore: a web tool for identifying altered pathways in cancer data. Bioinformatics 2016, 32: 3688-3690. PMID: 27503224, DOI: 10.1093/bioinformatics/btw512.Peer-Reviewed Original ResearchEarly 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
2008
HCLS 2.0/3.0: Health care and life sciences data mashup using Web 2.0/3.0
Cheung KH, Yip KY, Townsend JP, Scotch M. HCLS 2.0/3.0: Health care and life sciences data mashup using Web 2.0/3.0. Journal Of Biomedical Informatics 2008, 41: 694-705. PMID: 18487092, PMCID: PMC2933816, DOI: 10.1016/j.jbi.2008.04.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsBiological Science DisciplinesDatabase Management SystemsDelivery of Health CareEnvironmental PollutionGeographic Information SystemsHumansHypermediaInformation DisseminationInformation Storage and RetrievalInterdisciplinary CommunicationInternetNatural Language ProcessingNeoplasmsOligonucleotide Array Sequence AnalysisPublic Health InformaticsSoftware DesignSystems IntegrationUser-Computer InterfaceConceptsData mashupSemantic WebWeb 2.0Google MapsData integration tasksWeb 3.0 technologiesInformation system interfaceLife science domainWeb 2.0 technologiesWeb 2.0 toolsSet of technologiesGeographic information system interfaceMashup technologySemantic mashupWeb 2.0/3.0Data integrationMashupsSystem interfaceScience domainIntegration taskYahooHealth dataPublic health dataWebMicroarray research