Featured Publications
Premetastatic 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 cancer
2022
A 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
2019
APOBEC-induced mutations and their cancer effect size in head and neck squamous cell carcinoma
Cannataro VL, Gaffney SG, Sasaki T, Issaeva N, Grewal NKS, Grandis JR, Yarbrough WG, Burtness B, Anderson KS, Townsend JP. APOBEC-induced mutations and their cancer effect size in head and neck squamous cell carcinoma. Oncogene 2019, 38: 3475-3487. PMID: 30647454, PMCID: PMC6499643, DOI: 10.1038/s41388-018-0657-6.Peer-Reviewed Original ResearchConceptsPositive selectionCancer phenotypeStrong positive selectionIntensity of selectionEffects of mutationsBasis of mutationsSomatic genetic variantsSomatic evolutionNeutral driftMutational processesAPOBEC mutagenesisBiochemical experimentsSelection intensityMolecular understandingCytosine basesIndividual substitutionsAPOBEC3B proteinMutant stateMutational signaturesGenetic variantsNeck squamous cell carcinomaMutationsE545KGene variantsPhenotype
2014
Detecting rare gene transfer events in bacterial populations
Nielsen KM, Bøhn T, Townsend JP. Detecting rare gene transfer events in bacterial populations. Frontiers In Microbiology 2014, 4: 415. PMID: 24432015, PMCID: PMC3882822, DOI: 10.3389/fmicb.2013.00415.Peer-Reviewed Original ResearchHorizontal gene transferHGT eventsHost fitnessBacterial populationsDetection of HGTNew hostPopulation sizeGene transfer eventsKey population genetics parametersStrong positive selectionPopulation genetic parametersGene transfer mechanismsPopulation genetic modelingLarge population sizesGenetic diversityRelative population sizeGenetic compatibilityHGT ratesPositive selectionGenetic variationMutational processesNovel functionDonor organismHighlight knowledge gapsStructured populations