2025
KRAS G12C-associated immunotherapy benefit in NSCLC is substantially mediated by tobacco-induced tumor mutation burden, not allele-specific effects
Liu M, Townsend J. KRAS G12C-associated immunotherapy benefit in NSCLC is substantially mediated by tobacco-induced tumor mutation burden, not allele-specific effects. Lung Cancer 2025, 108749. DOI: 10.1016/j.lungcan.2025.108749.Peer-Reviewed Original ResearchNon-small cell lung cancerImmune-checkpoint inhibitionTumor mutational burdenMutational burdenG12C mutationLung adenocarcinomaElevated tumor mutation burdenHigh tumor mutational burdenOncogenic potentialCell lung cancerKRAS G12C mutationImmunotherapy benefitICI outcomesSmoking historyLung cancerG12D mutationHazard ratioAllele-specific effectsKRASClinical trendsKRAS G12CResponse rateTumorG12CMutationsTracing the evolution of single-cell 3D genomes in Kras-driven cancers
Liu M, Jin S, Agabiti S, Jensen T, Yang T, Radda J, Ruiz C, Baldissera G, Rajaei M, Li F, Townsend J, Muzumdar M, Wang S. Tracing the evolution of single-cell 3D genomes in Kras-driven cancers. Nature Genetics 2025, 1-13. PMID: 40825871, DOI: 10.1038/s41588-025-02297-w.Peer-Reviewed Original ResearchCell-to-cell heterogeneityGenome-wide chromatinGenome compactionGenome architectureGenomic structureGenome mappingGenome regulationLung adenocarcinomaDependent genesKRAS-driven cancersGenomeMouse lung adenocarcinomaCancer progressionEarly tumor progressionSingle cellsCancer stateGenesPancreatic ductal adenocarcinomaInvasive tumorsTherapeutic biomarkersDuctal adenocarcinomaTumor progressionCompartmental changesChromatinCancerApplying multilevel selection to understand cancer evolution and progression
Laplane L, Lamoureux A, Richker H, Alcaraz G, Fortunato A, Shaffer Z, Aktipis A, Mischel P, Plutynski A, Townsend J, Maley C. Applying multilevel selection to understand cancer evolution and progression. PLOS Biology 2025, 23: e3003290. PMID: 40680084, PMCID: PMC12303392, DOI: 10.1371/journal.pbio.3003290.Peer-Reviewed Original ResearchRates of Evolution of Developmental Changes in Gene Expression in Sordariomycetes
Wang Y, Wang F, Meng G, Lopez-Giraldez F, Dong C, Wang Z, Townsend J. Rates of Evolution of Developmental Changes in Gene Expression in Sordariomycetes. Molecular Biology And Evolution 2025, 42: msaf131. PMID: 40452442, PMCID: PMC12203517, DOI: 10.1093/molbev/msaf131.Peer-Reviewed Original ResearchConceptsRate of gene expression evolutionGene expression evolutionExpression evolutionGene expressionPhenotypic evolutionHeterogeneous rates of evolutionNonsynonymous to synonymous substitution ratesRates of phenotypic evolutionDevelopmental stagesSingle-copy orthologsGene sequence evolutionSynonymous substitution ratesRate of evolutionExpression of genesFunctional pathway analysisCarbon metabolismEvolutionary forcesConsequent phenotypesSexual reproductionSequence evolutionConserved pathwaysMeiosis pathwaysSubstitution ratesCell cyclePathway analysisPrecision projections of the delay of resistance mutations in non-small cell lung cancer via suppression of APOBEC
Nousias O, Mandell J, Anderson K, Townsend J. Precision projections of the delay of resistance mutations in non-small cell lung cancer via suppression of APOBEC. Lung Cancer 2025, 202: 108487. PMID: 40090261, DOI: 10.1016/j.lungcan.2025.108487.Peer-Reviewed Original ResearchNon-small cell lung cancer patientsNon-small cell lung cancerCell lung cancer patientsCell lung cancerLung cancer patientsEvolution of drug resistanceLung cancerDrug resistanceCancer patientsTyrosine kinase inhibitor therapyKinase inhibitor therapyTyrosine kinase inhibitorsPersonalized therapeutic strategiesTKI therapyInhibitor therapyTherapeutic failureResistance mutationsTherapeutic efficacyKinase inhibitorsAPOBEC mutationsTherapeutic strategiesTreatment efficacyCancer progressionImprove outcomesCancer
2024
Optimal Annual COVID-19 Vaccine Boosting Dates Following Previous Booster Vaccination or Breakthrough Infection
Townsend J, Hassler H, Dornburg A. Optimal Annual COVID-19 Vaccine Boosting Dates Following Previous Booster Vaccination or Breakthrough Infection. Clinical Infectious Diseases 2024, 80: 316-322. PMID: 39589144, PMCID: PMC11848277, DOI: 10.1093/cid/ciae559.Peer-Reviewed Original ResearchBooster vaccinationBooster administrationMortality associated with infectionHealthcare provider recommendationPrevention of infectionCases of infectionBreakthrough infectionCOVID-19 booster vaccinationTiming of booster vaccinationsProvider recommendationImmune statusBarriers to uptakePrevent infectionInfectionVaccination dateVaccineInfection rateBooster vaccination campaignsOptimal timingOptimal dateTranscription factor-dependent regulatory networks of sexual reproduction in Fusarium graminearum
Kim W, Kim D, Wang Z, Liu M, Townsend J, Trail F. Transcription factor-dependent regulatory networks of sexual reproduction in Fusarium graminearum. MBio 2024, 16: e03030-24. PMID: 39589130, PMCID: PMC11708053, DOI: 10.1128/mbio.03030-24.Peer-Reviewed Original ResearchMating-type locusSexual reproductionKnockout mutantsTranscription factorsTranscriptome dataStage of sexual developmentRegulatory networksTranscriptional cascadeDevelopmental phenotypesSexual developmentAscospore productionRegulation of sexual developmentUpstream activatorSexual fruiting bodiesTranscriptional regulatory cascadeMulticellular body planRegulate sexual developmentMultiple transcription factorsFusarium graminearumSystems biology approachComplex reproductive biologyEarly stages of sexual developmentArrest phenotypeTF networksFilamentous fungiCorrigendum: The Sordariomycetes: an expanding resource with Big Data for mining in evolutionary genomics and transcriptomics
Wang Z, Kim W, Wang Y, Yakubovich E, Dong C, Trail F, Townsend J, Yarden O. Corrigendum: The Sordariomycetes: an expanding resource with Big Data for mining in evolutionary genomics and transcriptomics. Frontiers In Fungal Biology 2024, 5: 1478516. PMID: 39228963, PMCID: PMC11368851, DOI: 10.3389/ffunb.2024.1478516.Peer-Reviewed Original ResearchRare Drivers at Low Prevalence with High Cancer Effects in T-Cell and B-Cell Pediatric Acute Lymphoblastic Leukemia
Mandell J, Diviti S, Xu M, Townsend J. Rare Drivers at Low Prevalence with High Cancer Effects in T-Cell and B-Cell Pediatric Acute Lymphoblastic Leukemia. International Journal Of Molecular Sciences 2024, 25: 6589. PMID: 38928295, PMCID: PMC11203805, DOI: 10.3390/ijms25126589.Peer-Reviewed Original ResearchGenomic analysisPediatric acute lymphoblastic leukemiaCancer effectsAcute lymphoblastic leukemiaT cellsTherapeutic targetSomatic substitutionsRare driversB-ALLLymphoblastic leukemiaEpistatic effectsT-cell ALL patientsMutational contributionsMutated genesCancer phenotypeMutated formDevelopment of leukemiaLow prevalenceB-cell lineageDisease mechanismsMutationsPrecision therapeuticsTherapeutic opportunitiesT-ALLALL patientsSufficient COVID-19 quarantine and testing on international travelers to forestall cross-border transmission after China's removal of the zero-COVID policy in early 2023
Bojja D, Zuo S, Townsend J. Sufficient COVID-19 quarantine and testing on international travelers to forestall cross-border transmission after China's removal of the zero-COVID policy in early 2023. International Journal Of Infectious Diseases 2024, 145: 107097. PMID: 38750721, DOI: 10.1016/j.ijid.2024.107097.Peer-Reviewed Original Research
2023
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 exclusivitySeasonality of endemic COVID-19
Townsend J, Hassler H, Lamb A, Sah P, Nishio A, Nguyen C, Tew A, Galvani A, Dornburg A. Seasonality of endemic COVID-19. MBio 2023, 14: e01426-23. PMID: 37937979, PMCID: PMC10746271, DOI: 10.1128/mbio.01426-23.Peer-Reviewed Original ResearchPublic health interventionsSARS-CoV-2Health interventionsSARS-CoV-2 infectionCOVID-19SARS-CoV-2 circulationEffective public health policiesLocal public health effortsEndemic COVID-19Public health effortsPublic healthPublic health policyLong-term dataCOVID-19 transmissionHealth effortsMedical preparednessVaccination driveHealth policyVaried interventionsEndemic diseaseSeasonal surgesInterventionInfectionEffective healthcareEndemic pathogensLineage-specific genes are clustered with HET-domain genes and respond to environmental and genetic manipulations regulating reproduction in Neurospora
Wang Z, Wang Y, Kasuga T, Lopez-Giraldez F, Zhang Y, Zhang Z, Wang Y, Dong C, Sil A, Trail F, Yarden O, Townsend J. Lineage-specific genes are clustered with HET-domain genes and respond to environmental and genetic manipulations regulating reproduction in Neurospora. PLOS Genetics 2023, 19: e1011019. PMID: 37934795, PMCID: PMC10684091, DOI: 10.1371/journal.pgen.1011019.Peer-Reviewed Original ResearchConceptsLineage-specific genesHET domain genesSexual reproductionFunctional roleUnusual carbon sourcesPotential functional roleMating lociAsexual growthGenetic mutantsNeurospora crassaPossible functional roleSexual phaseGenetic manipulationTranscriptomic profilingReproduction regulationGene knockoutPP-1ADV-1Environmental alterationsGenesSexual developmentNeurosporaReproductionCarbon sourceGenetic barrierOrigins of lineage‐specific elements via gene duplication, relocation, and regional rearrangement in Neurospora crassa
Wang Z, Wang Y, Kasuga T, Hassler H, Lopez‐Giraldez F, Dong C, Yarden O, Townsend J. Origins of lineage‐specific elements via gene duplication, relocation, and regional rearrangement in Neurospora crassa. Molecular Ecology 2023, 33: e17168. PMID: 37843462, PMCID: PMC11628664, DOI: 10.1111/mec.17168.Peer-Reviewed Original ResearchLineage-specific genesGene duplicationNew genesLineage-specific elementsWeighted gene correlation network analysisRecent gene duplicationNon-coding DNACell wall integrityCo-regulatory modulesGene correlation network analysisNon-coding sequencesCorrelation network analysisAntifungal toxinsGene syntenyNeurospora speciesGenus NeurosporaEvolutionary biologistsSuch cladesRegulatory machinerySequence repeatsModel speciesAncestral statusNeurospora crassaTranscriptomic dataDiverse functionsInfection 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 riskThe Sordariomycetes: an expanding resource with Big Data for mining in evolutionary genomics and transcriptomics
Wang Z, Kim W, Wang Y, Yakubovich E, Dong C, Trail F, Townsend J, Yarden O. The Sordariomycetes: an expanding resource with Big Data for mining in evolutionary genomics and transcriptomics. Frontiers In Fungal Biology 2023, 4: 1214537. PMID: 37746130, PMCID: PMC10512317, DOI: 10.3389/ffunb.2023.1214537.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsEvolutionary genomicsOmics dataFungal sexual developmentAncestral state analysisRichness of speciesDifferent taxonomic levelsAspects of biologySpecies/generaSystems biological analysisRegulatory network modelKnowledge of evolutionAscomycete genomesSordariomycetes classFungal evolutionTrait diversityDivergent lineagesFungal kingdomFungal biologyGenomic scaleSecondary metabolismModel genomesModel fungusModel speciesEcological diversityKey genetic elementsInfection 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 uptakeVaccineMortalityComparative Transcriptomics of Fusarium graminearum and Magnaporthe oryzae Spore Germination Leading up To Infection
Miguel-Rojas C, Cavinder B, Townsend J, Trail F. Comparative Transcriptomics of Fusarium graminearum and Magnaporthe oryzae Spore Germination Leading up To Infection. MBio 2023, 14: e02442-22. PMID: 36598191, PMCID: PMC9973345, DOI: 10.1128/mbio.02442-22.Peer-Reviewed Original ResearchConceptsComparative transcriptomicsMagnaporthe oryzaePlant surfacesFusarium graminearumF. graminearumGene expressionPlant pathogensAppressorium formationFungal plant pathogensComparative gene expressionBiosynthesis of deoxynivalenolHost-pathogen interfaceTrichothecene genesTrichome basesLaser dissection microscopyM. oryzaeFungal ingressTranscriptomic analysisInfection strategiesHelp of enzymesPlant cuticlesSpore germlingsTranscriptomicsMode of penetrationResistant cultivarsChapter 5 Measurement and meaning in gene expression evolution
Diaz R, Wang Z, Townsend J. Chapter 5 Measurement and meaning in gene expression evolution. 2023, 111-129. DOI: 10.1016/b978-0-323-91810-7.00008-x.ChaptersGene expressionPhenotypic evolutionGene expression evolutionMessenger RNAEffects of epistasisIndividual gene expressionRibonucleic acid sequencingExpression evolutionNonmodel speciesFunctional genomicsGenomic scaleTranscriptional networksGene functionRelative mRNA abundancePhenotypic variationPopulation geneticsReference genomeTranscriptome profilingBiological traitsMolecular adjustmentsQuantitative traitsPhenotypic varianceGene interactionsGenetic controlExpression variation
2022
Estimation 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
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