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 exclusivityCancer 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 tools
2023
Lineage-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 barrier
2022
Differential Expression of Cell Wall Remodeling Genes Is Part of the Dynamic Phase-Specific Transcriptional Program of Conidial Germination of Trichoderma asperelloides
Gortikov M, Yakubovich E, Wang Z, López-Giráldez F, Tu Y, Townsend JP, Yarden O. Differential Expression of Cell Wall Remodeling Genes Is Part of the Dynamic Phase-Specific Transcriptional Program of Conidial Germination of Trichoderma asperelloides. Journal Of Fungi 2022, 8: 854. PMID: 36012842, PMCID: PMC9410309, DOI: 10.3390/jof8080854.Peer-Reviewed Original ResearchPolar growthTranscript abundanceConidial germinationGlucanase-encoding geneOnset of germinationTranscriptional hubsTranscriptional programsTrichoderma asperelloidesHyphal growthTranscriptional profilesDevelopmental eventsChitin synthaseHost recognitionDifferential expressionGerminationSpecific membersDormant conidiaFirst branchingGenomeGenesInitial branchingAbundanceNetwork analysisExpressionMorphological progression
2020
Comparative Genomics within and across Bilaterians Illuminates the Evolutionary History of ALK and LTK Proto-Oncogene Origination and Diversification
Dornburg A, Wang Z, Wang J, Mo ES, López-Giráldez F, Townsend JP. Comparative Genomics within and across Bilaterians Illuminates the Evolutionary History of ALK and LTK Proto-Oncogene Origination and Diversification. Genome Biology And Evolution 2020, 13: evaa228. PMID: 33196781, PMCID: PMC7851593, DOI: 10.1093/gbe/evaa228.Peer-Reviewed Original ResearchConceptsLeukocyte tyrosine kinaseEvolutionary historyPhylogenetic analysisProtein-coding genesComparative genomic analysisEarly embryonic expressionMetazoan genomesComparative genomicsPhylogenetic contextModel organismsEmbryonic expressionModel speciesHuman genesKey genesGenomic analysisImportant genesMammal systemsFunctional convergenceTyrosine kinaseMolecular homologyGenesFunctional roleVertebratesMammal modelsHomology
2019
Comparative Genomics and Transcriptomics During Sexual Development Gives Insight Into the Life History of the Cosmopolitan Fungus Fusarium neocosmosporiellum
Kim W, Cavinder B, Proctor RH, O’Donnell K, Townsend JP, Trail F. Comparative Genomics and Transcriptomics During Sexual Development Gives Insight Into the Life History of the Cosmopolitan Fungus Fusarium neocosmosporiellum. Frontiers In Microbiology 2019, 10: 1247. PMID: 31231336, PMCID: PMC6568001, DOI: 10.3389/fmicb.2019.01247.Peer-Reviewed Original ResearchPolyketide synthase genesPerithecium developmentSynthase geneLife historySecondary metabolite gene clustersDiverse ecological nichesRoot rot pathogensComparative genomicsGene numberPlant pathogensLarger peritheciaGene clusterEcological nichesTransport genesMetabolic potentialGenomic underpinningsTranscriptomic analysisCosmopolitan fungusLarger ascosporesTransporter geneGenomeGenesNovel insightsField cropsSexual development
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 typesVariantsAnalysis 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 guidanceLvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira
Adhikarla H, Wunder EA, Mechaly AE, Mehta S, Wang Z, Santos L, Bisht V, Diggle P, Murray G, Adler B, Lopez F, Townsend JP, Groisman E, Picardeau M, Buschiazzo A, Ko AI. Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira. Frontiers In Cellular And Infection Microbiology 2018, 8: 45. PMID: 29600195, PMCID: PMC5863495, DOI: 10.3389/fcimb.2018.00045.Peer-Reviewed Original ResearchConceptsResponse regulatorTwo-component system proteinsDNA-binding response regulatorGlobal transcriptional regulationHybrid histidine kinaseGlobal gene regulationNovel signal pathwayComprehensive genomic analysisPhosphotransfer assaysTCS genesHistidine kinaseGene duplicationTranscriptional regulationGene regulationCorresponding genesPhylogenetic analysisGenomic analysisMolecular basisMutant strainSystem proteinsSignaling systemInfection processGenesBranched pathwayVirulence
2017
Light sensing by opsins and fungal ecology: NOP‐1 modulates entry into sexual reproduction in response to environmental cues
Wang Z, Wang J, Li N, Li J, Trail F, Dunlap JC, Townsend JP. Light sensing by opsins and fungal ecology: NOP‐1 modulates entry into sexual reproduction in response to environmental cues. Molecular Ecology 2017, 27: 216-232. PMID: 29134709, PMCID: PMC5797489, DOI: 10.1111/mec.14425.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceConserved SequenceEcological and Environmental PhenomenaFungal ProteinsGene Expression Regulation, FungalGene Knockout TechniquesGene Regulatory NetworksGenes, FungalLightModels, BiologicalMultienzyme ComplexesNADH, NADPH OxidoreductasesNeurospora crassaOpsinsOxidation-ReductionOxidative StressPhenotypePhylogenyProtein Structure, SecondaryReproductionUp-RegulationConceptsNOP-1Opsin-like proteinFungal ecologyPlant-associated fungiRapid environmental changeOxidative stress responseKey amino acidsFungal genomesComparative transcriptomicsSexual reproductionOrganismal functionNeurospora crassaEnvironmental cuesGenetic basisSensory rhodopsinStress responseNAD/NADPTransmembrane movementRetinal binding siteGenesAmino acidsFungiEnvironmental changesSexual developmentOpsin
2014
Genome-Wide Characterization of Light-Regulated Genes in Neurospora crassa
Wu C, Yang F, Smith KM, Peterson M, Dekhang R, Zhang Y, Zucker J, Bredeweg EL, Mallappa C, Zhou X, Lyubetskaya A, Townsend JP, Galagan JE, Freitag M, Dunlap JC, Bell-Pedersen D, Sachs MS. Genome-Wide Characterization of Light-Regulated Genes in Neurospora crassa. G3: Genes, Genomes, Genetics 2014, 4: 1731-1745. PMID: 25053707, PMCID: PMC4169166, DOI: 10.1534/g3.114.012617.Peer-Reviewed Original ResearchConceptsNeurospora crassaRNA-seqFilamentous fungus Neurospora crassaGenome-wide characterizationProtein coding genesFungus Neurospora crassaPrevious microarray studyRibosome biogenesisCoding genesTranscriptional responseRRNA metabolismCellular metabolismMicroarray studiesGenesCrassaSignificant oxidative stressRNA levelsOrganismsMRNA levelsOxidative stressMRNAMetabolismBiogenesisTranscriptsMycelium
2013
Phylogenetic and phylogenomic overview of the Polyporales
Binder M, Justo A, Riley R, Salamov A, Lopez-Giraldez F, Sjökvist E, Copeland A, Foster B, Sun H, Larsson E, Larsson KH, Townsend J, Grigoriev IV, Hibbett DS. Phylogenetic and phylogenomic overview of the Polyporales. Mycologia 2013, 105: 1350-1373. PMID: 23935031, DOI: 10.3852/13-003.Peer-Reviewed Original ResearchConceptsSingle-copy genePhylogenetic informativeness analysesResidual polyporoid cladeBayesian phylogenetic analysisPolyporales speciesMajor lineagesPhylogenomic datasetsAvailable genomesCorresponding cladesPhlebioid cladePolyporoid cladeNew genomesGenome dataPhylogenetic analysisSuprageneric taxonomyCertain taxaPhylogenetic systematicsGenomic datasetsIdentical topologiesPolyporalesGenomeCladeSupport valuesGenesLineagesSex-linked transcriptional divergence in the hermaphrodite fungus Neurospora tetrasperma
Samils N, Gioti A, Karlsson M, Sun Y, Kasuga T, Bastiaans E, Wang Z, Li N, Townsend JP, Johannesson H. Sex-linked transcriptional divergence in the hermaphrodite fungus Neurospora tetrasperma. Proceedings Of The Royal Society B 2013, 280: 20130862. PMID: 23782882, PMCID: PMC3712418, DOI: 10.1098/rspb.2013.0862.Peer-Reviewed Original ResearchConceptsMating typesFilamentous ascomycete Neurospora tetraspermaNeurospora tetraspermaMating-type locusGene expression levelsExpression divergenceTranscriptional divergencePhenotypic divergenceFungal AnaloguesRecombinational suppressionMat ASequence divergenceN. tetraspermaMale developmentDivergent regionsFemale developmentMolecular phenotypesGenesSexual dimorphismMale tissuesExpression levelsDivergencePhenotypeAgar mediumGenomeEpidemiological mechanisms of genetic resistance to kuru
Atkins KE, Townsend JP, Medlock J, Galvani AP. Epidemiological mechanisms of genetic resistance to kuru. Journal Of The Royal Society Interface 2013, 10: 20130331. PMID: 23740487, PMCID: PMC4043168, DOI: 10.1098/rsif.2013.0331.Peer-Reviewed Original ResearchConceptsTransmissible spongiform encephalopathiesGenotype frequency dataPopulation geneticsProtein geneGenetic resistanceEpidemiological mechanismsPrion protein geneMechanistic basisPrion proteinHost resistanceFatal neurodegenerative conditionHuman populationHuman resistancePapua New GuineaNew GuineaSpongiform encephalopathiesIncubation periodCodon 129Neurodegenerative conditionsIncidence dataReduced susceptibilityLong incubation periodKuruGenesMechanismEvaluating Phylogenetic Informativeness as a Predictor of Phylogenetic Signal for Metazoan, Fungal, and Mammalian Phylogenomic Data Sets
López-Giráldez F, Moeller AH, Townsend JP. Evaluating Phylogenetic Informativeness as a Predictor of Phylogenetic Signal for Metazoan, Fungal, and Mammalian Phylogenomic Data Sets. BioMed Research International 2013, 2013: 621604. PMID: 23878813, PMCID: PMC3708382, DOI: 10.1155/2013/621604.Peer-Reviewed Original ResearchConceptsPhylogenomic data setsPhylogenetic informativenessPhylogenetic signalEffects of homoplasyPoor phylogenetic resolutionPhylogenetic resolutionSister cladeOutgroup taxaPhylogenetic researchTaxonomic groupsPhylogenetic inferenceAdvantageous genesGenesMetazoansCladeTaxaDiverse groupDiverse time scalesHomoplasyHaphazard samplingMammalsFungiOrganismsFungalMarkers
2012
Sex-specific gene expression during asexual development of Neurospora crassa
Wang Z, Kin K, López-Giráldez F, Johannesson H, Townsend JP. Sex-specific gene expression during asexual development of Neurospora crassa. Fungal Genetics And Biology 2012, 49: 533-543. PMID: 22626843, PMCID: PMC3397379, DOI: 10.1016/j.fgb.2012.05.004.Peer-Reviewed Original ResearchConceptsMating-type genesAsexual developmentMating typesNeurospora crassaGene expressionSex-specific gene expressionFungal life historyLight-responsive genesOverall gene expressionExpression levelsDifferent mating typesExpression of pheromonePheromone genesHigh expression levelsMat AType genesLife historyResponse genesExpression differencesDevelopment stagesGenesClonal developmentImpact of lightReceptor geneCrassaRBE controls microRNA164 expression to effect floral organogenesis
Huang T, López-Giráldez F, Townsend JP, Irish VF. RBE controls microRNA164 expression to effect floral organogenesis. Development 2012, 139: 2161-2169. PMID: 22573623, DOI: 10.1242/dev.075069.Peer-Reviewed Original ResearchConceptsCUP-SHAPED COTYLEDON1Zinc finger transcriptional repressorKey transcriptional regulatorMiR164 expressionPetal organogenesisArabidopsis flowersPetal developmentPlant developmentEffector genesTranscriptional regulatorsTranscriptional repressorFloral organogenesisGene productsDevelopmental eventsConcomitant regulationGenesOrgan boundariesOrganogenesisExpressionMiR164cCUC2RepressorBoundary specificationPromoterFlowersCodon Deviation Coefficient: a novel measure for estimating codon usage bias and its statistical significance
Zhang Z, Li J, Cui P, Ding F, Li A, Townsend JP, Yu J. Codon Deviation Coefficient: a novel measure for estimating codon usage bias and its statistical significance. BMC Bioinformatics 2012, 13: 43. PMID: 22435713, PMCID: PMC3368730, DOI: 10.1186/1471-2105-13-43.Peer-Reviewed Original ResearchConceptsCodon usage biasNucleotide compositionUsage biasGenome evolutionGene functionProtein functionCodon usageNatural selectionCodon positionsTranslational efficiencySelective pressureSequence compositionGene expressionSequence analysisSimulated sequencesSequenceGenomeGenesFundamental importanceMutationsInformative estimationExpressionPhylogenetic Signal and Noise: Predicting the Power of a Data Set to Resolve Phylogeny
Townsend JP, Su Z, Tekle YI. Phylogenetic Signal and Noise: Predicting the Power of a Data Set to Resolve Phylogeny. Systematic Biology 2012, 61: 835-849. PMID: 22389443, DOI: 10.1093/sysbio/sys036.Peer-Reviewed Original ResearchConceptsPhylogenetic signalPhylogenetic noisePhylogenetic treeAdditional sequence dataRate of evolutionPhylogenetic researchPhylogenetic experimental designSequence dataImpact of collectionInternodesPower of resolutionFundamental unitTreesPhylogeneticsPhylogenyPolytomyGenesLociPotential signalsSignalsExample data setsData setsAbundant Gene-by-Environment Interactions in Gene Expression Reaction Norms to Copper within Saccharomyces cerevisiae
Hodgins-Davis A, Adomas AB, Warringer J, Townsend JP. Abundant Gene-by-Environment Interactions in Gene Expression Reaction Norms to Copper within Saccharomyces cerevisiae. Genome Biology And Evolution 2012, 4: 1061-1079. PMID: 23019066, PMCID: PMC3514956, DOI: 10.1093/gbe/evs084.Peer-Reviewed Original ResearchMeSH KeywordsCluster AnalysisCopperDNA-Binding ProteinsDose-Response Relationship, DrugGene Expression ProfilingGene Expression Regulation, FungalGene-Environment InteractionGenes, FungalGenetic VariationMetabolic Networks and PathwaysMicroarray AnalysisNuclear ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscription FactorsTranscriptomeConceptsPopulation variationReaction normsGene expression reaction normsGene expressionNovel ecological contextsGenome-wide mRNA levelsGenetic backgroundRelevant copper concentrationsAbundance of variationMitotic fitnessSulfur homeostasisPlastic phenotypesDownstream metabolic consequencesPlastic variationMost genesCopper stressPhenotypic variationGene networksAbundant genesGenetic variationCopper gradientExpression variationEcological contextDifferential expressionGenes