Featured Publications
The durability of natural infection and vaccine-induced immunity against future infection by SARS-CoV-2
Townsend JP, Hassler HB, Sah P, Galvani AP, Dornburg A. The durability of natural infection and vaccine-induced immunity against future infection by SARS-CoV-2. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2204336119. PMID: 35858382, PMCID: PMC9351502, DOI: 10.1073/pnas.2204336119.Peer-Reviewed Original ResearchThe durability of immunity against reinfection by SARS-CoV-2: a comparative evolutionary study
Townsend JP, Hassler HB, Wang Z, Miura S, Singh J, Kumar S, Ruddle NH, Galvani AP, Dornburg A. The durability of immunity against reinfection by SARS-CoV-2: a comparative evolutionary study. The Lancet Microbe 2021, 2: e666-e675. PMID: 34632431, PMCID: PMC8486316, DOI: 10.1016/s2666-5247(21)00219-6.Peer-Reviewed Original ResearchConceptsDurability of immunitySARS-CoV-2Human-infecting coronavirusesProbability of reinfectionAntibody levelsMERS-CoVSARS-CoVLong-term immune responsePeak antibody responsePublic health decision makingCOVID-19 pandemic continuesEndemic conditionsCOVID-19 morbidityPublic health measuresVirus SARS-CoVHealth decision makingOptical density levelsDevastating COVID-19 pandemicAntibody declineLikely reinfectionAntibody responseEndemic coronavirusesHCoV-NL63Immune responseHuman coronavirusesTesting for COVID-19 is Much More Effective When Performed Immediately Prior to Social Mixing
Wells CR, Gokcebel S, Pandey A, Galvani AP, Townsend JP. Testing for COVID-19 is Much More Effective When Performed Immediately Prior to Social Mixing. International Journal Of Public Health 2022, 67: 1604659. PMID: 35967267, PMCID: PMC9363582, DOI: 10.3389/ijph.2022.1604659.Peer-Reviewed Original ResearchAPOBEC mutagenesis and selection for NFE2L2 contribute to the origin of lung squamous-cell carcinoma
Cannataro VL, Kudalkar S, Dasari K, Gaffney SG, Lazowski HM, Jackson LK, Yildiz I, Das RK, Rothberg BE, Anderson KS, Townsend JP. APOBEC mutagenesis and selection for NFE2L2 contribute to the origin of lung squamous-cell carcinoma. Lung Cancer 2022, 171: 34-41. PMID: 35872531, PMCID: PMC10126952, DOI: 10.1016/j.lungcan.2022.07.004.Peer-Reviewed Original ResearchConceptsCytidine deaminationMutagenic processesDefective homologous recombinationGenomic sequencesHomologous recombinationAttractive potential targetAPOBEC mutagenesisLung squamous cell carcinomaDeamination activityCancer cell growthAPOBEC proteinsAPOBEC activityCell growthCellular proliferationNFE2L2MutationsMolecular investigationsCancer effectsPotential targetMolecular variantsAPOBECSurvival of cancerSquamous cell carcinomaDeaminationVariantsAttribution 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 lineagesProliferationPremetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma
Fisk JN, Mahal AR, Dornburg A, Gaffney SG, Aneja S, Contessa JN, Rimm D, Yu JB, Townsend JP. Premetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma. Cancer Letters 2021, 526: 346-351. PMID: 34780851, PMCID: PMC8702484, DOI: 10.1016/j.canlet.2021.11.011.Peer-Reviewed Original ResearchConceptsMutational processesSingle ancestral lineageAncestral lineageProgression of cancerMetastatic lineagesPhylogenetic analysisGenetic resistanceEvolutionary processesExogenous mutational processesCancer evolutionConsolidative therapyMutational signature analysisEGFR-positive non-small cell lung cancerNon-small cell lung cancerKey eventsLineagesCell populationsTherapeutic resistanceLocal consolidative therapyClinical time courseCell lung cancerDisease etiologyTherapeutic decision makingCisplatin therapyLung cancerHeavy mutagenesis by tobacco leads to lung adenocarcinoma tumors with KRAS G12 mutations other than G12D, leading KRAS G12D tumors—on average—to exhibit a lower mutation burden
Tan C, Mandell JD, Dasari K, Cannataro VL, Alfaro-Murillo JA, Townsend JP. Heavy mutagenesis by tobacco leads to lung adenocarcinoma tumors with KRAS G12 mutations other than G12D, leading KRAS G12D tumors—on average—to exhibit a lower mutation burden. Lung Cancer 2021, 166: 265-269. PMID: 34736794, DOI: 10.1016/j.lungcan.2021.10.008.Peer-Reviewed Original ResearchThe Prognostic Value of an RT-PCR Test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Is Contingent on Timing across Disease Time Course in addition to Assay Sensitivity
Townsend JP, Wells CR. The Prognostic Value of an RT-PCR Test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Is Contingent on Timing across Disease Time Course in addition to Assay Sensitivity. Journal Of Molecular Diagnostics 2021, 24: 101-103. PMID: 34974875, PMCID: PMC8717055, DOI: 10.1016/j.jmoldx.2021.10.002.Peer-Reviewed Original ResearchEnvironmental and sex-specific molecular signatures of glioma causation
Claus EB, Cannataro VL, Gaffney SG, Townsend JP. Environmental and sex-specific molecular signatures of glioma causation. Neuro-Oncology 2021, 24: 29-36. PMID: 33942853, PMCID: PMC8730771, DOI: 10.1093/neuonc/noab103.Peer-Reviewed Original ResearchConceptsIDH wild-type tumorsWild-type tumorsEnvironmental risk factorsIDH-mutant tumorsRisk factorsCases of gliomaMolecular signaturesPIK3CA mutationsPossible risk exposuresMutation subtypesCancer effectsExogenous exposureAdult gliomasTumorsWhole-exome sequencing dataGliomasKinase domainMutational signaturesCancer-causing mutationsMalesFemalesNon-coding regionsPIK3R1SexCancer mutational signaturesOptimal COVID-19 quarantine and testing strategies
Wells CR, Townsend JP, Pandey A, Moghadas SM, Krieger G, Singer B, McDonald RH, Fitzpatrick MC, Galvani AP. Optimal COVID-19 quarantine and testing strategies. Nature Communications 2021, 12: 356. PMID: 33414470, PMCID: PMC7788536, DOI: 10.1038/s41467-020-20742-8.Peer-Reviewed Original ResearchInfection 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 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 mutationsInfection by SARS‐CoV‐2 with alternate frequencies of mRNA vaccine boosting
Townsend J, Hassler H, Dornburg A. Infection by SARS‐CoV‐2 with alternate frequencies of mRNA vaccine boosting. Journal Of Medical Virology 2023, 95: e28461. PMID: 36602045, DOI: 10.1002/jmv.28461.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Anti-spike IgG antibodiesWaning of antibodiesVaccine boostingBooster vaccinationBreakthrough infectionsAntibody levelsIgG antibodiesMRNA vaccinesProbability of infectionInfectionEndemic transmissionIndividual infectionsPredominant variantCOVID-19 pandemicMessenger RNAAntibodiesDisease spreadBNT162b2HospitalizationMorbidityVaccinationWidespread uptakeVaccineMortality
2022
Not only mutations but also tumorigenesis can be substantially attributed to DNA damage from reactive oxygen species in RUNX1::RUNX1T1-fusion-positive acute myeloid leukemia
Mandell J, Fisk J, Cyrenne E, Xu M, Cannataro V, Townsend J. Not only mutations but also tumorigenesis can be substantially attributed to DNA damage from reactive oxygen species in RUNX1::RUNX1T1-fusion-positive acute myeloid leukemia. Leukemia 2022, 36: 2931-2933. PMID: 36369483, PMCID: PMC9712081, DOI: 10.1038/s41375-022-01752-5.Peer-Reviewed Original ResearchPlacing 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 approachFamilyA phylogenetic approach to study the evolution of somatic mutational processes in cancer
Miura S, Vu T, Choi J, Townsend JP, Karim S, Kumar S. A phylogenetic approach to study the evolution of somatic mutational processes in cancer. Communications Biology 2022, 5: 617. PMID: 35732905, PMCID: PMC9217972, DOI: 10.1038/s42003-022-03560-0.Peer-Reviewed Original ResearchConceptsMutational processesPattern of conservationFalse-positive discovery rateCollection of mutationsSomatic mutational processesPhylogenetic approachGenomic variationSomatic variationCell lineagesMutational signaturesTumor evolutionMutation signaturesPhylogenyCancer cellsDiscovery rateMutationsComputer-simulated datasetsRelative activityLineagesComputational methodsSignaturesConservationDivergenceEvolutionJoint analysis
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