2022
Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes
Montal V, Diez I, Kim C, Orwig W, Bueichekú E, Gutiérrez-Zúñiga R, Bejanin A, Pegueroles J, Dols-Icardo O, Vannini P, El-Fakhri G, Johnson K, Sperling R, Fortea J, Sepulcre J. Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes. Science Translational Medicine 2022, 14: eabn7273. PMID: 35895837, PMCID: PMC9942690, DOI: 10.1126/scitranslmed.abn7273.Peer-Reviewed Original ResearchConceptsTau spreadingIntracellular accumulation of tau proteinAccumulation of tau proteinAlzheimer's diseasePathological tau accumulationGenetic gradientGenetic dataTau proteinNeurofibrillary tanglesSynaptic genesTau accumulationGenetic traitsGenesDrug development strategiesExpression gradientIntracellular accumulationTauExpressionCognitively normal older participantsHuman brain cortexTanglesProteinApoTraitsAlzheimerNeurogenetic traits outline vulnerability to cortical disruption in Parkinson’s disease
Basaia S, Agosta F, Diez I, Bueichekú E, Uquillas F, Delgado-Alvarado M, Caballero-Gaudes C, Rodriguez-Oroz M, Stojkovic T, Kostic V, Filippi M, Sepulcre J. Neurogenetic traits outline vulnerability to cortical disruption in Parkinson’s disease. NeuroImage Clinical 2022, 33: 102941. PMID: 35091253, PMCID: PMC8800137, DOI: 10.1016/j.nicl.2022.102941.Peer-Reviewed Original ResearchConceptsParkinson's diseaseBrain circuitsGene expression patternsBrain connectivityPD-related pathologyPD participantsHuman brainHuman cortexTopological intersectionConnectivity networksCortical propagation patternsPostmortem dataGenetic traitsBrainExpression patternsSNCA geneConnectivity trajectoriesGenesCellular componentsNeuronal damageNeuronal vulnerabilityVulnerabilityParkinsonTraits
2021
Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration
Jimenez‐Marin A, Diez I, Labayru G, Sistiaga A, Caballero M, Andres‐Benito P, Sepulcre J, Ferrer I, de Munain A, Cortes J. Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration. Neuropathology And Applied Neurobiology 2021, 47: 1092-1108. PMID: 33955002, PMCID: PMC9292638, DOI: 10.1111/nan.12725.Peer-Reviewed Original ResearchConceptsMicrotubule-associated protein tauAllen Human Brain AtlasRNA analysisSynaptic vesicle recyclingSynaptic vesicle genesHypothesis-driven genesGene clusterDopamine neurotransmitter pathwaysVesicle recyclingProtein tauTranscriptome mapTranscriptome interactionsTau pathologyMyotonic dystrophy type IBrain degenerationBiological processesGenesHuman Brain AtlasAlzheimer's diseaseTranscriptional signatureNeurobiological mechanismsCognitive functionAlpha-synucleinNeurotransmitter pathwaysRNAUnveiling the neuroimaging-genetic intersections in the human brain
Diez I, Sepulcre J. Unveiling the neuroimaging-genetic intersections in the human brain. Current Opinion In Neurology 2021, 34: 480-487. PMID: 34227572, PMCID: PMC8265485, DOI: 10.1097/wco.0000000000000952.Peer-Reviewed Original ResearchConceptsSingle-cell transcriptomic dataExpression of genesFunctional annotationGenetic networksGenetic dataTranscriptome dataTranscriptomic datasetsBrain genesGenesBrain phenotypesBrain expressionBiological mechanismsNeuroimaging workNeuroimaging mapsBrain-wideNeuroimaging findingsLife spanExpressionTranscriptomeHuman brainNeuroimaging
2020
Linking Lysosomal Enzyme Targeting Genes and Energy Metabolism with Altered Gray Matter Volume in Children with Persistent Stuttering
Chow H, Garnett E, Li H, Etchell A, Sepulcre J, Drayna D, Chugani D, Chang S. Linking Lysosomal Enzyme Targeting Genes and Energy Metabolism with Altered Gray Matter Volume in Children with Persistent Stuttering. Neurobiology Of Language 2020, 1: 365-380. PMID: 34041495, PMCID: PMC8138901, DOI: 10.1162/nol_a_00017.Peer-Reviewed Original ResearchGray matter volume differencesGray matter volumeParticipating genomesMatter volumeTarget genesExpression patternsPersistent stutteringGene expression dataEnergy metabolismGene expression patternsGene set enrichment analysisVolume differencesVoxel-based morphometryChildhood-onset neurodevelopmental disorderExpression dataIntracellular traffickingEnrichment analysisGene expressionGenesDevelopmental stutteringFluent peersNeuroanatomical changesStuttering casesBrain structuresAllen Institute for Brain Science
2019
Neurofilament-lysosomal genetic intersections in the cortical network of stuttering
Benito-Aragón C, Gonzalez-Sarmiento R, Liddell T, Diez I, d'Oleire Uquillas F, Ortiz-Terán L, Bueichekú E, Chow H, Chang S, Sepulcre J. Neurofilament-lysosomal genetic intersections in the cortical network of stuttering. Progress In Neurobiology 2019, 184: 101718. PMID: 31669185, PMCID: PMC6938554, DOI: 10.1016/j.pneurobio.2019.101718.Peer-Reviewed Original ResearchConceptsCytoskeleton organizationNeurofilament genesCortical networksGenetic expression levelsMannose-6-phosphateGenetic interactomesInteractome networkTranscriptome dataLarge-scale cortical networksLysosomal pathwayAllen Human Brain AtlasPresence of stutteringGenetic intersectionFunctional connectivity MRIBiological functionsNeuronal circuitsSpatial similarity analysisGenesHuman Brain AtlasTarget pathwaysFunctional linkInteractomeNeurobiological underpinningsCo-localizationLysosomal dysfunction
2018
Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain
Xin Q, Ortiz-Terán L, Diez I, Perez D, Ginsburg J, Fakhri G, Sepulcre J. Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain. Cerebral Cortex 2018, 29: 3828-3835. PMID: 30307489, PMCID: PMC6686751, DOI: 10.1093/cercor/bhy262.Peer-Reviewed Original ResearchConceptsGenetic sequence alterationsGene expression profilesSequence alterationsGenetic expression dataExpression profilesBrain regionsFunctional connectivity variabilityCortical genesCortical regionsAllen Brain AtlasExpression dataGenetic variationGenetic signaturesFunctional connectivity magnetic resonance imagingCortical areasDiscrete cortical regionsGenesGraph theory analysisFunctional profilesNeurobiological underpinningsSequenceDegree of individual variabilityBrain areasBrain individualizationBrain organization
2016
Increased expression of dedicator-cytokinesis-10, caspase-2 and Synaptotagmin-like 2 is associated with clinical disease activity in multiple sclerosis
Agirrezabal I, Palacios R, Moreno B, Sepulcre J, Abernathy A, Saiz A, Llufriu S, Comabella M, Montalban X, Martinez A, Arteta D, Villoslada P. Increased expression of dedicator-cytokinesis-10, caspase-2 and Synaptotagmin-like 2 is associated with clinical disease activity in multiple sclerosis. Multiple Sclerosis And Demyelinating Disorders 2016, 1: 7. DOI: 10.1186/s40893-016-0009-8.Peer-Reviewed Original ResearchRelapsing-remitting multiple sclerosisCaspase-2Gene OntologyTranscription factorsAnalysis of regulatory networksDisease activityLymphocyte activationAssociated with clinical disease activityGene tripletsRegulatory networksClinical disease activityCohort of MS patientsDNA arraysCo-regulationJASPAR databaseMAPKinase pathwayDEGsStable patientsProspective cohortDisability accumulationHealthy controlsClinical activityMS patientsTranscriptionGenes
2008
A computational analysis of protein-protein interaction networks in neurodegenerative diseases
Goñi J, Esteban F, de Mendizábal N, Sepulcre J, Ardanza-Trevijano S, Agirrezabal I, Villoslada P. A computational analysis of protein-protein interaction networks in neurodegenerative diseases. BMC Systems Biology 2008, 2: 52. PMID: 18570646, PMCID: PMC2443111, DOI: 10.1186/1752-0509-2-52.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsAnalysis of protein-protein interaction networksProtein-protein interaction informationProtein-protein interaction networkAlzheimer's diseaseNeurodegenerative diseasesProtein-protein interaction analysisSeed proteinStudy of biological networksGene expression studiesDNA array experimentsProperties of proteinsMultifactorial neurodegenerative diseaseAD brainInteraction networkExpression studiesBiological networksGene expressionBackgroundRecent developmentsMolecular pathwaysGenesArray experimentsComputational analysisParameters of degreePathway