{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T05:48:21Z","timestamp":1768888101802,"version":"3.49.0"},"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["412854449"],"award-info":[{"award-number":["412854449"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Description of robust transcriptomic alterations in Huntington\u2019s disease is essential to identify targets for biochemical studies and drug development. We analysed publicly available transcriptome data from the brain and blood of 220 HD patients and 241 healthy controls and identified 737 and 661 genes with robustly altered mRNA levels in the brain and blood of HD patients, respectively. In the brain, a subnetwork of 320 genes strongly correlated with HD and was enriched in transport-related genes. Bioinformatical analysis of this subnetwork highlighted CDC42, PAK1, YWHAH, NFY, DLX1, HMGN3, and PRMT3. Moreover, we found that CREB1 can regulate 78.0% of genes whose mRNA levels correlated with HD in the blood of patients. Alterations in protein transport, metabolism, transcriptional regulation, and CDC42-mediated functions are likely central features of HD. Further our data substantiate the role of transcriptional regulators that have not been reported in the context of HD (e.g. DLX1, HMGN3 and PRMT3) and strongly suggest dysregulation of NFY and its target genes across tissues. A large proportion of the identified genes such as CDC42 were also altered in Parkinson\u2019s (PD) and Alzheimer\u2019s disease (AD). The observed dysregulation of CDC42 and YWHAH in samples from HD, AD and PD patients indicates that those genes and their upstream regulators may be interesting therapeutic targets.<\/jats:p>","DOI":"10.1371\/journal.pone.0253037","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T23:39:03Z","timestamp":1623368343000},"page":"e0253037","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":29,"title":["A meta-analysis of transcriptomic profiles of Huntington\u2019s disease patients"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6581-1419","authenticated-orcid":true,"given":"Manuel","family":"Seefelder","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Kochanek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"pone.0253037.ref001","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.neuron.2016.02.003","article-title":"The Biology of Huntingtin","volume":"89","author":"F Saudou","year":"2016","journal-title":"Neuron"},{"key":"pone.0253037.ref002","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes","volume":"72","author":"The Huntington\u2019s Disease Collaborative Research Group","year":"1993","journal-title":"Cell"},{"key":"pone.0253037.ref003","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S1474-4422(10)70245-3","article-title":"Huntington\u2019s disease: from molecular pathogenesis to clinical treatment","volume":"10","author":"CA Ross","year":"2011","journal-title":"The Lancet Neurology"},{"key":"pone.0253037.ref004","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S1474-4422(09)70178-4","article-title":"Beyond the brain: widespread pathology in Huntington\u2019s disease","volume":"8","author":"JMM van der Burg","year":"2009","journal-title":"The Lancet Neurology"},{"key":"pone.0253037.ref005","first-page":"243","volume-title":"Huntington\u2019s disease","author":"C Zuccato","year":"2014","edition":"4"},{"key":"pone.0253037.ref006","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neuron.2012.05.024","article-title":"Network organization of the huntingtin proteomic interactome in mammalian brain","volume":"75","author":"DI Shirasaki","year":"2012","journal-title":"Neuron"},{"key":"pone.0253037.ref007","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.it.2015.04.007","article-title":"The choreography of neuroinflammation in Huntington\u2019s disease","volume":"36","author":"A Crotti","year":"2015","journal-title":"Trends Immunol"},{"key":"pone.0253037.ref008","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/1531-8249(199901)45:1<25::AID-ART6>3.0.CO;2-E","article-title":"Biochemical abnormalities and excitotoxicity in Huntington\u2019s disease brain","volume":"45","author":"SJ Tabrizi","year":"1999","journal-title":"Ann Neurol"},{"key":"pone.0253037.ref009","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.pneurobio.2006.11.003","article-title":"N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington\u2019s disease","volume":"81","author":"MMY Fan","year":"2007","journal-title":"Prog Neurobiol"},{"key":"pone.0253037.ref010","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.4161\/rna.26706","article-title":"Aberrantly spliced HTT, a new player in Huntington\u2019s disease pathogenesis","volume":"10","author":"TA Gipson","year":"2013","journal-title":"RNA Biol"},{"key":"pone.0253037.ref011","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S0968-0004(03)00168-3","article-title":"The hunt for huntingtin function: interaction partners tell many different stories","volume":"28","author":"P Harjes","year":"2003","journal-title":"Trends in Biochemical Sciences"},{"key":"pone.0253037.ref012","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1006\/exnr.1998.6832","article-title":"Wild-type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways","volume":"152","author":"J Velier","year":"1998","journal-title":"Exp Neurol"},{"key":"pone.0253037.ref013","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s12920-019-0581-9","article-title":"The caudate nucleus undergoes dramatic and unique transcriptional changes in human prodromal Huntington\u2019s disease brain","volume":"12","author":"F Agus","year":"2019","journal-title":"BMC Med Genomics"},{"key":"pone.0253037.ref014","doi-asserted-by":"crossref","first-page":"e0143563","DOI":"10.1371\/journal.pone.0143563","article-title":"RNA Sequence Analysis of Human Huntington Disease Brain Reveals an Extensive Increase in Inflammatory and Developmental Gene Expression","volume":"10","author":"A Labadorf","year":"2015","journal-title":"PLoS ONE"},{"key":"pone.0253037.ref015","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3389\/fnmol.2017.00430","article-title":"Evidence for a Pan-Neurodegenerative Disease Response in Huntington\u2019s and Parkinson\u2019s Disease Expression Profiles","volume":"10","author":"A Labadorf","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"pone.0253037.ref016","doi-asserted-by":"crossref","first-page":"743","DOI":"10.15252\/msb.20145304","article-title":"Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases","volume":"10","author":"M Narayanan","year":"2014","journal-title":"Mol Syst Biol"},{"key":"pone.0253037.ref017","doi-asserted-by":"crossref","first-page":"17141","DOI":"10.1073\/pnas.1104409108","article-title":"Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington disease activity in man and mouse","volume":"108","author":"Y Hu","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0253037.ref018","doi-asserted-by":"crossref","first-page":"14424","DOI":"10.1073\/pnas.0703652104","article-title":"Analysis of potential transcriptomic biomarkers for Huntington\u2019s disease in peripheral blood","volume":"104","author":"H Runne","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0253037.ref019","doi-asserted-by":"crossref","first-page":"11023","DOI":"10.1073\/pnas.0504921102","article-title":"Genome-wide expression profiling of human blood reveals biomarkers for Huntington\u2019s disease","volume":"102","author":"F Borovecki","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0253037.ref020","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12920-014-0060-2","article-title":"A common gene expression signature in Huntington\u2019s disease patient brain regions","volume":"2014","author":"A Neueder","year":"2014","journal-title":"BMC Med Genomics"},{"key":"pone.0253037.ref021","doi-asserted-by":"crossref","first-page":"42875","DOI":"10.1038\/srep42875","article-title":"Altered enhancer transcription underlies Huntington\u2019s disease striatal transcriptional signature","volume":"7","author":"S Le Gras","year":"2017","journal-title":"Sci Rep."},{"key":"pone.0253037.ref022","doi-asserted-by":"crossref","first-page":"6763","DOI":"10.1073\/pnas.100110097","article-title":"The Huntington\u2019s disease protein interacts with p53 and CREB-binding protein and represses transcription","volume":"97","author":"JS Steffan","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0253037.ref023","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1093\/hmg\/9.14.2197","article-title":"CREB-binding protein sequestration by expanded polyglutamine","volume":"9","author":"A McCampbell","year":"2000","journal-title":"Hum Mol Genet"},{"key":"pone.0253037.ref024","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0166-2236(00)01609-X","article-title":"Transcriptional dysregulation in Huntington\u2019s disease","volume":"23","author":"JH Cha","year":"2000","journal-title":"Trends Neurosci"},{"key":"pone.0253037.ref025","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0168-9525(03)00074-X","article-title":"Transcriptional abnormalities in Huntington disease","volume":"19","author":"KL Sugars","year":"2003","journal-title":"Trends Genet"},{"key":"pone.0253037.ref026","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/bpa.12427","article-title":"RNA toxicity induced by expanded CAG repeats in Huntington\u2019s disease","volume":"26","author":"E. Mart\u00ed","year":"2016","journal-title":"Brain Pathol"},{"key":"pone.0253037.ref027","doi-asserted-by":"crossref","first-page":"e752","DOI":"10.1038\/cddis.2013.276","article-title":"Mechanisms of RNA-induced toxicity in CAG repeat disorders","volume":"4","author":"R Nalavade","year":"2013","journal-title":"Cell Death Dis"},{"key":"pone.0253037.ref028","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"D Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pone.0253037.ref029","doi-asserted-by":"crossref","first-page":"37527","DOI":"10.1074\/jbc.M604342200","article-title":"Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas","volume":"281","author":"K Modzelewska","year":"2006","journal-title":"J Biol Chem"},{"key":"pone.0253037.ref030","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1083\/jcb.200408085","article-title":"Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis","volume":"168","author":"F Oceguera-Yanez","year":"2005","journal-title":"J Cell Biol"},{"key":"pone.0253037.ref031","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1091\/mbc.e03-07-0493","article-title":"Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs","volume":"15","author":"C Gauthier-Campbell","year":"2004","journal-title":"Mol Biol Cell"},{"key":"pone.0253037.ref032","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/367040a0","article-title":"A brain serine\/threonine protein kinase activated by Cdc42 and Rac1","volume":"367","author":"E Manser","year":"1994","journal-title":"Nature"},{"key":"pone.0253037.ref033","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1423-0127-18-12","article-title":"Functional characterization of Trip10 in cancer cell growth and survival","volume":"18","author":"C-C Hsu","year":"2011","journal-title":"J Biomed Sci"},{"key":"pone.0253037.ref034","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1073\/pnas.0437967100","article-title":"Cdc42-interacting protein 4 binds to huntingtin: neuropathologic and biological evidence for a role in Huntington\u2019s disease","volume":"100","author":"S Holbert","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0253037.ref035","doi-asserted-by":"crossref","first-page":"38249","DOI":"10.1038\/srep38249","article-title":"Rab14 specifies the apical membrane through Arf6-mediated regulation of lipid domains and Cdc42","volume":"6","author":"R Lu","year":"2016","journal-title":"Sci Rep"},{"key":"pone.0253037.ref036","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.ajhg.2018.09.005","article-title":"Activating Mutations in PAK1, Encoding p21-Activated Kinase 1, Cause a Neurodevelopmental Disorder","volume":"103","author":"FL Harms","year":"2018","journal-title":"Am J Hum Genet"},{"key":"pone.0253037.ref037","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13041-019-0436-5","article-title":"Gene expression meta-analysis of Parkinson\u2019s disease and its relationship with Alzheimer\u2019s disease","volume":"12","author":"J Kelly","year":"2019","journal-title":"Mol Brain"},{"key":"pone.0253037.ref038","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"P Shannon","year":"2003","journal-title":"Genome Res"},{"key":"pone.0253037.ref039","doi-asserted-by":"crossref","first-page":"W214","DOI":"10.1093\/nar\/gkq537","article-title":"The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function","volume":"38","author":"D Warde-Farley","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"pone.0253037.ref040","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nrm974","article-title":"Sorting out the cellular functions of sorting nexins","volume":"3","author":"CA Worby","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pone.0253037.ref041","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1152\/physrev.00006.2017","article-title":"The Arp2\/3 Regulatory System and Its Deregulation in Cancer","volume":"98","author":"N Molinie","year":"2018","journal-title":"Physiol Rev"},{"key":"pone.0253037.ref042","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1080\/21541248.2016.1215657","article-title":"Cdc42 in actin dynamics: An ordered pathway governed by complex equilibria and directional effector handover","volume":"8","author":"JR Watson","year":"2017","journal-title":"Small GTPases"},{"key":"pone.0253037.ref043","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fnsyn.2019.00003","article-title":"Altered Regulation of Striatal Neuronal N-Methyl-D-Aspartate Receptor Trafficking by Palmitoylation in Huntington Disease Mouse Model","volume":"11","author":"R Kang","year":"2019","journal-title":"Front Synaptic Neurosci"},{"key":"pone.0253037.ref044","doi-asserted-by":"crossref","first-page":"9768","DOI":"10.1074\/jbc.RA120.012983","article-title":"FACS-array-based cell purification yields a specific transcriptome of striatal medium spiny neurons in a murine Huntington disease model","volume":"295","author":"H Miyazaki","year":"2020","journal-title":"J Biol Chem"},{"key":"pone.0253037.ref045","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1093\/hmg\/ddq018","article-title":"Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis","volume":"19","author":"K Becanovic","year":"2010","journal-title":"Hum Mol Genet"},{"key":"pone.0253037.ref046","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nn.4256","article-title":"Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice","volume":"19","author":"P Langfelder","year":"2016","journal-title":"Nat Neurosci"},{"key":"pone.0253037.ref047","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1091\/mbc.e03-09-0639","article-title":"RNAi-mediated Hip1R silencing results in stable association between the endocytic machinery and the actin assembly machinery","volume":"15","author":"AEY Engqvist-Goldstein","year":"2004","journal-title":"Mol Biol Cell"},{"key":"pone.0253037.ref048","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/sj.emboj.7601576","article-title":"A Hip1R-cortactin complex negatively regulates actin assembly associated with endocytosis","volume":"26","author":"C Le Clainche","year":"2007","journal-title":"EMBO J"},{"key":"pone.0253037.ref049","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/jnc.13703","article-title":"Huntingtin-associated protein-1 is a synapsin I-binding protein regulating synaptic vesicle exocytosis and synapsin I trafficking","volume":"138","author":"KD Mackenzie","year":"2016","journal-title":"J Neurochem"},{"key":"pone.0253037.ref050","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.cellsig.2017.02.023","article-title":"Huntingtin-associated protein-1 (HAP1) regulates endocytosis and interacts with multiple trafficking-related proteins","volume":"35","author":"KD Mackenzie","year":"2017","journal-title":"Cell Signal"},{"key":"pone.0253037.ref051","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-94-007-0763-4_3","article-title":"Role of SNAREs in membrane fusion","volume":"713","author":"BP Jena","year":"2011","journal-title":"Adv Exp Med Biol"},{"key":"pone.0253037.ref052","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3233\/JHD-130080","article-title":"Striatal synaptosomes from Hdh140Q\/140Q knock-in mice have altered protein levels, novel sites of methionine oxidation, and excess glutamate release after stimulation","volume":"2","author":"A Valencia","year":"2013","journal-title":"J Huntingtons Dis"},{"key":"pone.0253037.ref053","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1471-4159.2007.04703.x","article-title":"Loss of SNAP-25 and rabphilin 3a in sensory-motor cortex in Huntington\u2019s disease","volume":"103","author":"R Smith","year":"2007","journal-title":"J Neurochem"},{"key":"pone.0253037.ref054","doi-asserted-by":"crossref","first-page":"4510","DOI":"10.1093\/hmg\/ddu166","article-title":"Progressive axonal transport and synaptic protein changes correlate with behavioral and neuropathological abnormalities in the heterozygous Q175 KI mouse model of Huntington\u2019s disease","volume":"23","author":"GA Smith","year":"2014","journal-title":"Hum Mol Genet"},{"key":"pone.0253037.ref055","doi-asserted-by":"crossref","first-page":"e82","DOI":"10.1371\/journal.pgen.0030082","article-title":"Huntingtin interacting proteins are genetic modifiers of neurodegeneration","volume":"3","author":"LS Kaltenbach","year":"2007","journal-title":"PLoS Genet"},{"key":"pone.0253037.ref056","first-page":"20","article-title":"The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin","author":"M Seefelder","year":"2020","journal-title":"BMC Evolutionary Biology"},{"key":"pone.0253037.ref057","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1128\/MCB.00969-10","article-title":"p21-Activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties","volume":"31","author":"W Huang","year":"2011","journal-title":"Mol Cell Biol"},{"key":"pone.0253037.ref058","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1242\/jcs.050013","article-title":"Huntingtin promotes cell survival by preventing Pak2 cleavage","volume":"122","author":"S Luo","year":"2009","journal-title":"J Cell Sci"},{"key":"pone.0253037.ref059","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1093\/hmg\/ddm362","article-title":"p21-activated kinase 1 promotes soluble mutant huntingtin self-interaction and enhances toxicity","volume":"17","author":"S Luo","year":"2008","journal-title":"Hum Mol Genet"},{"key":"pone.0253037.ref060","doi-asserted-by":"crossref","first-page":"6709","DOI":"10.1074\/jbc.M113.523696","article-title":"A large scale Huntingtin protein interaction network implicates Rho GTPase signaling pathways in Huntington disease","volume":"289","author":"C Tourette","year":"2014","journal-title":"J Biol Chem"},{"key":"pone.0253037.ref061","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng882","article-title":"Disruption of CREB function in brain leads to neurodegeneration","volume":"31","author":"T Mantamadiotis","year":"2002","journal-title":"Nat Genet"},{"key":"pone.0253037.ref062","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"M Uhl\u00e9n","year":"2015","journal-title":"Science"},{"key":"pone.0253037.ref063","doi-asserted-by":"crossref","first-page":"19176","DOI":"10.1073\/pnas.0606373103","article-title":"ESET\/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington\u2019s disease","volume":"103","author":"H Ryu","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0253037.ref064","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1186\/s12864-017-3745-z","article-title":"The dynamics of early-state transcriptional changes and aggregate formation in a Huntington\u2019s disease cell model","volume":"18","author":"M van Hagen","year":"2017","journal-title":"BMC Genomics"},{"key":"pone.0253037.ref065","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/emboj.2008.23","article-title":"Mutant Huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factor","volume":"27","author":"T Yamanaka","year":"2008","journal-title":"EMBO J"},{"key":"pone.0253037.ref066","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.3349\/ymj.2003.44.6.1059","article-title":"Characterization of the two genes differentially expressed during development in human fetal astrocytes","volume":"44","author":"SS Lee","year":"2003","journal-title":"Yonsei Med J"},{"key":"pone.0253037.ref067","doi-asserted-by":"crossref","first-page":"7418","DOI":"10.1073\/pnas.1921007117","article-title":"Parcellation of the striatal complex into dorsal and ventral districts","volume":"117","author":"S-Y Chen","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0253037.ref068","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1093\/cercor\/bhx241","article-title":"Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis","volume":"28","author":"R Pla","year":"2018","journal-title":"Cereb Cortex"},{"key":"pone.0253037.ref069","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/ejn.12413","article-title":"Dlx1 transcription factor regulates dendritic growth and postsynaptic differentiation through inhibition of neuropilin-2 and PAK3 expression","volume":"39","author":"X Dai","year":"2014","journal-title":"Eur J Neurosci"},{"key":"pone.0253037.ref070","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.brainres.2010.07.033","article-title":"PRMT3 is essential for dendritic spine maturation in rat hippocampal neurons","volume":"1352","author":"S Miyata","year":"2010","journal-title":"Brain Res"},{"key":"pone.0253037.ref071","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1016\/j.neuroscience.2006.05.022","article-title":"Immunohistochemical and western analyses of protein arginine N-methyltransferase 3 in the mouse brain","volume":"141","author":"K Ikenaka","year":"2006","journal-title":"Neuroscience"},{"key":"pone.0253037.ref072","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.nbd.2009.05.007","article-title":"Systematic behavioral evaluation of Huntington\u2019s disease transgenic and knock-in mouse models","volume":"35","author":"L Menalled","year":"2009","journal-title":"Neurobiol Dis"},{"key":"pone.0253037.ref073","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/978-1-4939-7825-0_6","article-title":"Mouse Models of Huntington\u2019s Disease","volume":"1780","author":"PP Farshim","year":"2018","journal-title":"Methods Mol Biol"},{"key":"pone.0253037.ref074","first-page":"74","article-title":"Imputation with the R Package VIM","author":"A Kowarik","year":"2016","journal-title":"J Stat Soft."},{"key":"pone.0253037.ref075","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11634-011-0102-y","article-title":"Exploring incomplete data using visualization techniques","volume":"6","author":"M Templ","year":"2012","journal-title":"Adv Data Anal Classif"},{"key":"pone.0253037.ref076","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S1525-1578(10)60455-2","article-title":"Analysis of Microarray Data Using Z Score Transformation","volume":"5","author":"C Cheadle","year":"2003","journal-title":"The Journal of Molecular Diagnostics"},{"key":"pone.0253037.ref077","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/bioinformatics\/btr709","article-title":"Robust rank aggregation for gene list integration and meta-analysis","volume":"28","author":"R Kolde","year":"2012","journal-title":"Bioinformatics"},{"key":"pone.0253037.ref078","author":"GR Warnes","year":"2020","journal-title":"gplots: Various R Programming Tools for Plotting Data"},{"key":"pone.0253037.ref079","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"P Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"pone.0253037.ref080","first-page":"4","article-title":"A general framework for weighted gene co-expression network analysis","author":"B Zhang","year":"2005","journal-title":"Stat Appl Genet Mol Biol"},{"key":"pone.0253037.ref081","doi-asserted-by":"crossref","first-page":"289","DOI":"10.32614\/RJ-2016-021","article-title":"mclust 5: Clustering, Classification and Density Estimation Using Gaussian Finite Mixture Models","volume":"8","author":"L Scrucca","year":"2016","journal-title":"The R Journal"},{"key":"pone.0253037.ref082","first-page":"1165","article-title":"The control of the false discovery rate in multiple testing under dependency","volume":"29","author":"D Yekutieli","year":"2001","journal-title":"Ann Statist"},{"key":"pone.0253037.ref083","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"M Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"pone.0253037.ref084","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1186\/s12859-016-1203-6","article-title":"NEAT: an efficient network enrichment analysis test","volume":"17","author":"M Signorelli","year":"2016","journal-title":"BMC Bioinformatics"},{"key":"pone.0253037.ref085","doi-asserted-by":"crossref","first-page":"W212","DOI":"10.1093\/nar\/gkz446","article-title":"ChEA3: transcription factor enrichment analysis by orthogonal omics integration","volume":"47","author":"AB Keenan","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pone.0253037.ref086","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria; 2020."},{"key":"pone.0253037.ref087","volume-title":"ggplot2. Elegant graphics for data analysis","author":"H. Wickham","year":"2016"},{"issue":"4","key":"pone.0253037.ref088","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1186\/1752-0509-8-S4-S11","article-title":"cytoHubba: identifying hub objects and sub-networks from complex interactome","volume":"8","author":"C-H Chin","year":"2014","journal-title":"BMC Syst Biol"},{"key":"pone.0253037.ref089","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: an open-source package for R and S+ to analyze and compare ROC curves","volume":"12","author":"X Robin","year":"2011","journal-title":"BMC Bioinformatics"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T19:37:26Z","timestamp":1699126646000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253037"}},"subtitle":[],"editor":[{"given":"Xiao-Hong","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,6,10]]},"references-count":89,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0253037","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,10]]}}}