2025
APOBEC affects tumor evolution and age at onset of lung cancer in smokers
Zhang T, Sang J, Hoang P, Zhao W, Rosenbaum J, Johnson K, Klimczak L, McElderry J, Klein A, Wirth C, Bergstrom E, Díaz-Gay M, Vangara R, Colon-Matos F, Hutchinson A, Lawrence S, Cole N, Zhu B, Przytycka T, Shi J, Caporaso N, Homer R, Pesatori A, Consonni D, Imielinski M, Chanock S, Wedge D, Gordenin D, Alexandrov L, Harris R, Landi M. APOBEC affects tumor evolution and age at onset of lung cancer in smokers. Nature Communications 2025, 16: 4711. PMID: 40394004, PMCID: PMC12092836, DOI: 10.1038/s41467-025-59923-8.Peer-Reviewed Original ResearchConceptsLung cancerTumor evolutionMulti-omics profilingLung tumor samplesCell of originProgenitor-like cellsMulti-OmicsMutagenic processesMutational processesOff-target activityTP53 mutationsMutational burdenSignaling pathwayKRAS mutationsMutagenesisAPOBEC mutagenesisSomatic mutationsSolid tumorsTumor samplesClonal expansionDNA damageTumor developmentCell typesMutationsStemness markersIntegrative Plasma Multi-Omics Profiling Reveals Novel Mechanisms of Pulmonary Arterial Hypertension
Kheyfets V, Sweatt A, Zhang H, Nemkov T, Aizin M, Heerdt P, Dzieciatkowska M, Stephenson D, LaCroix I, D'Alessandro A, Oldham W, Hansen K, Zamanian R, Stenmark K. Integrative Plasma Multi-Omics Profiling Reveals Novel Mechanisms of Pulmonary Arterial Hypertension. American Journal Of Respiratory And Critical Care Medicine 2025, 211: a7246-a7246. DOI: 10.1164/ajrccm.2025.211.abstracts.a7246.Peer-Reviewed Original Research
2024
Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder
Zillich E, Belschner H, Avetyan D, Andrade-Brito D, Martínez-Magaña J, Frank J, Mechawar N, Turecki G, Cabana-Domínguez J, Fernàndez-Castillo N, Cormand B, Montalvo-Ortiz J, Nöthen M, Hansson A, Rietschel M, Spanagel R, Witt S, Zillich L. Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder. Translational Psychiatry 2024, 14: 428. PMID: 39384764, PMCID: PMC11464785, DOI: 10.1038/s41398-024-03139-9.Peer-Reviewed Original ResearchConceptsCocaine use disorderUse disorderAlternative splicingHuman prefrontal cortexProfiling of DNA methylationBrodmann area 9Differential alternative splicingDeregulated biological processesPostmortem brain tissueMulti-omics approachCocaine intakeMulti-omics studiesPrefrontal cortexBrain alterationsMulti-omics profilingGene expression alterationsArea 9Fatty acid metabolismReceptor-targeting drugsSpliced transcriptsEpigenome-wideDNA methylationNeuronal morphogenesisAS changesDrug repositioning analysisExposome-Wide Ranking to Uncover Environmental Chemicals Associated with Dyslipidemia: A Panel Study in Healthy Older Chinese Adults from the BAPE Study.
Ding E, Deng F, Fang J, Liu J, Yan W, Yao Q, Miao K, Wang Y, Sun P, Li C, Liu Y, Dong H, Dong L, Zhang X, Lu Y, Lin X, Ding C, Li T, Shi Y, Cai Y, Liu X, Godri Pollitt K, Ji J, Tong S, Tang S, Shi X. Exposome-Wide Ranking to Uncover Environmental Chemicals Associated with Dyslipidemia: A Panel Study in Healthy Older Chinese Adults from the BAPE Study. Environmental Health Perspectives 2024, 132: 97005. PMID: 39240788, PMCID: PMC11379127, DOI: 10.1289/ehp13864.Peer-Reviewed Original ResearchConceptsDyslipidemia markersCardiovascular diseaseMulti-OmicsMarkers of dyslipidemiaExamination of cytokinesMeasurement of cytokinesSerum lipidomeSystemic inflammationMulti-omics profilingCardiac functionDyslipidemiaPrimary preventionClinical measuresSerumChinese adultsBlood transcriptomeImpact spectraCytokinesExposome-wide association studyInflammationMarkersBiomolecular pathwaysAssociationHealthy older adultsElectrocardiogramA systems vaccinology resource to develop and test computational models of immunity
Shinde P, Willemsen L, Orfield S, Kojima M, Reyna J, Ha B, Greenbaum J, Overton J, Nili S, Rasmussen M, Gygi J, Antunes R, Sette A, Olsen L, Grant B, Konstorum A, Guan L. A systems vaccinology resource to develop and test computational models of immunity. The Journal Of Immunology 2024, 212: 1571_5604-1571_5604. DOI: 10.4049/jimmunol.212.supp.1571.5604.Peer-Reviewed Original ResearchMulti-Omics Profiling of Human Hippocampus Reveals Increased Inflammation and Transcription Instability in Major Depressive Disorder
Xiao Y, Mariani M, Su G, Deng Y, Sissoko C, Li T, Ma S, Bai Z, Liu Y, Rosoklija G, Wu T, Dwork A, Hen R, Mann J, Fan R, Leong K, Boldrini M. Multi-Omics Profiling of Human Hippocampus Reveals Increased Inflammation and Transcription Instability in Major Depressive Disorder. Biological Psychiatry 2024, 95: s68-s69. DOI: 10.1016/j.biopsych.2024.02.168.Peer-Reviewed Original Research
2023
TMIC-20. A SPATIALLY RESOLVED HUMAN GLIOBLASTOMA ATLAS REVEALS DISTINCT CELLULAR AND MOLECULAR PATTERNS OF ANATOMICAL NICHES
Shah N, Park H, Sonpatki P, Han K, Yu H, Kim S, Chowdhury T, Byun Y, Kang H, Lee J, Lee S, Won J, Kim T, Choi S, Shin Y, Ku J, Lee S, Yun H, Park S, Park C, Park W. TMIC-20. A SPATIALLY RESOLVED HUMAN GLIOBLASTOMA ATLAS REVEALS DISTINCT CELLULAR AND MOLECULAR PATTERNS OF ANATOMICAL NICHES. Neuro-Oncology 2023, 25: v282-v282. PMCID: PMC10639919, DOI: 10.1093/neuonc/noad179.1086.Peer-Reviewed Original ResearchCellular componentsBulk RNA-seq dataAnatomical nichesSingle-cell atlasSingle-cell RNARNA-seq dataMulti-omics profilingDifferent cellular componentsInteraction networksSpatial transcriptomeCellular heterogeneitySpatial interaction networkDistinct cellularMolecular patternsCellular architectureNicheUnrecognized subtypesSpatial organizationAbstract GlioblastomaValuable resourceGlioma samplesStromal cellsEffective combinatorial therapiesComprehensive insightGlioblastomaMulti-omic profiling of the developing human cerebral cortex at the single-cell level
Zhu K, Bendl J, Rahman S, Vicari J, Coleman C, Clarence T, Latouche O, Tsankova N, Li A, Brennand K, Lee D, Yuan G, Fullard J, Roussos P. Multi-omic profiling of the developing human cerebral cortex at the single-cell level. Science Advances 2023, 9: eadg3754. PMID: 37824614, PMCID: PMC10569714, DOI: 10.1126/sciadv.adg3754.Peer-Reviewed Original ResearchConceptsCis-regulatory elementsChromatin accessibilityGene expressionPseudotime trajectory analysisNeuronal lineage commitmentMulti-omics profilingSingle-cell levelSpecific genetic lociDevelopmental time pointsChromatin structureType-specific domainsLineage determinationCellular complexityLineage commitmentNeuropsychiatric traitsComplex regulationGenetic lociSpatiotemporal activityDynamic changesCritical roleExpressionSpatiotemporal alterationsCell compositionCritical stageNeuropsychiatric diseasesMulti-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells
Wang Y, Popovic Z, Charkoftaki G, Garcia-Milian R, Lam T, Thompson D, Chen Y, Vasiliou V. Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells. Chemico-Biological Interactions 2023, 384: 110714. PMID: 37716420, PMCID: PMC10807983, DOI: 10.1016/j.cbi.2023.110714.Peer-Reviewed Original ResearchColon cancer cellsCellular stress response pathwaysStress response pathwaysMulti-omics analysisCancer cellsSecond messenger signalingMulti-omics profilingNew molecular informationFunctional annotationCellular functionsResponse pathwaysKinase signalingCellular pathwaysColon adenocarcinoma cell lineHuman colon adenocarcinoma cell lineApoptosis signalingEnrichment analysisAldehyde dehydrogenase 1B1Molecular signaturesAdenocarcinoma cell lineMolecular informationSignalingNovel targetProtein expressionCell linesProfiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex
Rompala G, Nagamatsu S, Martínez-Magaña J, Nuñez-Ríos D, Wang J, Girgenti M, Krystal J, Gelernter J, Hurd Y, Montalvo-Ortiz J. Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex. Nature Communications 2023, 14: 4544. PMID: 37507366, PMCID: PMC10382503, DOI: 10.1038/s41467-023-40285-y.Peer-Reviewed Original ResearchConceptsOpioid use disorderMulti-omics findingsGene expression patternsCo-methylation analysisGene expression profilesMulti-omics profilingGene networksDNA methylationNeuronal methylomesDNA hydroxymethylationMethylomic analysisExpression patternsExpression profilesEpigenetic disturbancesUse disordersPsychiatric traitsOrbitofrontal cortexOpioid-related drugsPostmortem orbitofrontal cortexEnvironmental factorsDrug interaction analysisOUD treatmentHuman orbitofrontal cortexOpioid signalingInteraction analysisMulti-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature
Li Q, Feng T, Zhu T, Zhang W, Qian Y, Zhang H, Zheng X, Li D, Yun X, Zhao J, Li Y, Yu H, Gao M, Qian B. Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature. Journal Of Translational Medicine 2023, 21: 206. PMID: 36941725, PMCID: PMC10026500, DOI: 10.1186/s12967-023-04045-2.Peer-Reviewed Original ResearchConceptsTCGA patientsPositive thyroglobulin antibodiesPapillary thyroid microcarcinomaNew therapeutic hypothesesUnique transcriptomic signaturesImmune-related genesWhole-exome sequencingImmune interventionPeroxidase antibodiesThyroglobulin antibodiesEtiology of cancerRET fusionsThyroid microcarcinomaTCGA cohortBRAF mutationsPatientsDifferent somatic mutationsMulti-omics profilingLarger studyConclusionsOur findingsResultsIn additionExome sequencingTherapeutic hypothesesTranscriptomic signaturesMolecular landscapeComprehensive multi-omic profiling of somatic mutations in malformations of cortical development
Chung C, Yang X, Bae T, Vong K, Mittal S, Donkels C, Westley Phillips H, Li Z, Marsh A, Breuss M, Ball L, Garcia C, George R, Gu J, Xu M, Barrows C, James K, Stanley V, Nidhiry A, Khoury S, Howe G, Riley E, Xu X, Copeland B, Wang Y, Kim S, Kang H, Schulze-Bonhage A, Haas C, Urbach H, Prinz M, Limbrick D, Gurnett C, Smyth M, Sattar S, Nespeca M, Gonda D, Imai K, Takahashi Y, Chen H, Tsai J, Conti V, Guerrini R, Devinsky O, Silva W, Machado H, Mathern G, Abyzov A, Baldassari S, Baulac S, Gleeson J. Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development. Nature Genetics 2023, 55: 209-220. PMID: 36635388, PMCID: PMC9961399, DOI: 10.1038/s41588-022-01276-9.Peer-Reviewed Original ResearchConceptsSingle-nucleus RNA sequencingSpatiotemporal expression patternsSomatic mutationsTarget amplicon sequencingLow allelic fractionsMulti-omics profilingGene setsRNA sequencingFunctional validationCellular organizationExpression patternsGenotype-phenotype correlation analysisGenetic landscapeCortical developmentMutationsGenetic causeUtero electroporationSomatic mosaic mutationsGenesCritical roleMosaic mutationsSequencingNeuronal hyperexcitabilityBrain resectionProfiling
2022
Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine
Cotero V, Graf J, Miwa H, Hirschstein Z, Qanud K, Huerta TS, Tai N, Ding Y, Jimenez-Cowell K, Tomaio JN, Song W, Devarajan A, Tsaava T, Madhavan R, Wallace K, Loghin E, Morton C, Fan Y, Kao TJ, Akhtar K, Damaraju M, Barenboim L, Maietta T, Ashe J, Tracey KJ, Coleman TR, Di Carlo D, Shin D, Zanos S, Chavan SS, Herzog RI, Puleo C. Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine. Nature Biomedical Engineering 2022, 6: 683-705. PMID: 35361935, PMCID: PMC10127248, DOI: 10.1038/s41551-022-00870-w.Peer-Reviewed Original ResearchConceptsGlucose homeostasisGlucose toleranceNerve plexusAfferent autonomic nervesHyperinsulinemic euglycaemic clampNon-pharmacologic therapiesType 2 diabetesInsulin-resistant diabetesHepatic portal systemAutonomic nervesNerve pathwaysDiabetic miceFocused ultrasound stimulationPeripheral neuronsSensory projectionsIntestinal tissueMetabolic diseasesMulti-omics profilingPortal systemMetabolic tissuesGlucose availabilityDiabetesSelective activationPlexusUltrasound stimulation
2020
DeepCDR: a hybrid graph convolutional network for predicting cancer drug response
Liu Q, Hu Z, Jiang R, Zhou M. DeepCDR: a hybrid graph convolutional network for predicting cancer drug response. Bioinformatics 2020, 36: i911-i918. PMID: 33381841, DOI: 10.1093/bioinformatics/btaa822.Peer-Reviewed Original ResearchConceptsCancer drug responsePredicting cancer drug responseDrug responseAnti-cancer drug designCancer-associated genesMulti-omics profilingSupplementary dataHybrid graph convolutional networkDrug designTranscriptome profilingOmics profilesCancer cellsCancer biologyChemical structures of drugsBioinformaticsProfile of individual patientsGraph convolutional networkCancer typesBonding of drugHeterogeneity of cancer patientsConvolutional networkIntrinsic chemical structuresStructure of drugsFeatures of drugsGenesTransformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease
Wang M, Li A, Sekiya M, Beckmann ND, Quan X, Schrode N, Fernando MB, Yu A, Zhu L, Cao J, Lyu L, Horgusluoglu E, Wang Q, Guo L, Wang YS, Neff R, Song WM, Wang E, Shen Q, Zhou X, Ming C, Ho SM, Vatansever S, Kaniskan HÜ, Jin J, Zhou MM, Ando K, Ho L, Slesinger PA, Yue Z, Zhu J, Katsel P, Gandy S, Ehrlich ME, Fossati V, Noggle S, Cai D, Haroutunian V, Iijima KM, Schadt E, Brennand KJ, Zhang B. Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease. Neuron 2020, 109: 257-272.e14. PMID: 33238137, PMCID: PMC7855384, DOI: 10.1016/j.neuron.2020.11.002.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseAlzheimer's diseaseKey regulatorPluripotent stem cell-derived neuronsRNAi-based knockdownStem cell-derived neuronsNovel therapeutic targetNext-generation therapeutic agentsCell-derived neuronsKey brain regionsIntegrative network analysisMulti-omics dataComplex molecular interactionsMulti-omics profilingNCH-51Neuronal impairmentGene subnetworksDisease-related processesCortical areasTherapeutic targetDrosophila modelNeuropathological phenotypeBrain regionsTherapeutic agentsMolecular mechanisms
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