2023
More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome
Minteer C, Thrush K, Gonzalez J, Niimi P, Rozenblit M, Rozowsky J, Liu J, Frank M, McCabe T, Sehgal R, Higgins-Chen A, Hofstatter E, Pusztai L, Beckman K, Gerstein M, Levine M. More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome. Science Advances 2023, 9: eadf4163. PMID: 37467337, PMCID: PMC10355820, DOI: 10.1126/sciadv.adf4163.Peer-Reviewed Original ResearchConceptsStem cell divisionImmortalized human cellsTissue-specific cancer riskTumorigenic stateCell divisionDNA methylationEpigenetic changesAge-related accumulationHuman cellsMultiple tissuesSomatic mutationsClinical tissuesTissue differencesEpigenomeCellsTissueNormal tissuesMethylationMutationsReplicationNormal breast tissueSignaturesVitroAccumulationDivision
2020
NIMBus: a negative binomial regression based Integrative Method for mutation Burden Analysis
Zhang J, Liu J, McGillivray P, Yi C, Lochovsky L, Lee D, Gerstein M. NIMBus: a negative binomial regression based Integrative Method for mutation Burden Analysis. BMC Bioinformatics 2020, 21: 474. PMID: 33092526, PMCID: PMC7580035, DOI: 10.1186/s12859-020-03758-1.Peer-Reviewed Original ResearchConceptsDNase I hypersensitive sitesMutation rate heterogeneityDNA elementsCancer whole genome sequencesMutational hotspotsMutation burden analysisFunctional genomics dataNon-coding regionsGene regulatory networksWhole Genomes (PCAWG) projectWhole genome sequencesBackground mutation rateBurden analysisChromatin organizationReplication timingGenome sequenceRegulatory networksTranscription factorsHypersensitive sitesGenomic featuresRate heterogeneityGenome ProjectGenomic dataIntegrative methodGamma-Poisson mixture modelAn integrative ENCODE resource for cancer genomics
Zhang J, Lee D, Dhiman V, Jiang P, Xu J, McGillivray P, Yang H, Liu J, Meyerson W, Clarke D, Gu M, Li S, Lou S, Xu J, Lochovsky L, Ung M, Ma L, Yu S, Cao Q, Harmanci A, Yan KK, Sethi A, Gürsoy G, Schoenberg MR, Rozowsky J, Warrell J, Emani P, Yang YT, Galeev T, Kong X, Liu S, Li X, Krishnan J, Feng Y, Rivera-Mulia JC, Adrian J, Broach JR, Bolt M, Moran J, Fitzgerald D, Dileep V, Liu T, Mei S, Sasaki T, Trevilla-Garcia C, Wang S, Wang Y, Zang C, Wang D, Klein RJ, Snyder M, Gilbert DM, Yip K, Cheng C, Yue F, Liu XS, White KP, Gerstein M. An integrative ENCODE resource for cancer genomics. Nature Communications 2020, 11: 3696. PMID: 32728046, PMCID: PMC7391744, DOI: 10.1038/s41467-020-14743-w.Peer-Reviewed Original ResearchConceptsCell typesFunctional genomics datasetsEffect of MycStem-like stateNetwork-based annotationUncharacterized RBPsOncogenic TFSTARR-seqOncogene knockdownTranscription factorsGenomic datasetsOncogenic transformationGenome interpretationUniversal annotationCancer genomicsDifferential expressionSiRNA knockdownLuciferase assayTargeted validationRegulatorTumor transitionCustom annotationsAnnotationKnockdownCoherent workflow