{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T20:13:52Z","timestamp":1783196032879,"version":"3.54.6"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T00:00:00Z","timestamp":1558310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21AG061646"],"award-info":[{"award-number":["R21AG061646"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS081301"],"award-info":[{"award-number":["R01NS081301"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that culminates in paralysis and death. Here, we present our analyses of publicly available multiOMIC data sets generated using motor neurons from ALS patients and control cohorts. Functional annotation of differentially expressed genes in induced pluripotent stem cell (iPSC)-derived motor neurons generated from patients with mutations in C9ORF72 (C9-ALS) suggests elevated expression of genes that pertain to extracellular matrix (ECM) and cell adhesion, inflammation and TGF\u03b2 targets. On the other end of the continuum, we detected diminished expression of genes repressed by quiescence-promoting E2F4\/DREAM complex. Proteins whose abundance was significantly altered in C9-ALS neurons faithfully recapitulated the transcriptional aberrations. Importantly, patterns of gene expression in spinal motor neurons dissected from C9-ALS or sporadic ALS patients were highly concordant with each other and with the C9-ALS iPSC neurons. In contrast, motor neurons from patients with mutations in SOD1 exhibited dramatically different signatures. Elevated expression of gene sets such as ECM and cell adhesion genes occurs in C9 and sporadic ALS but not SOD1-ALS. These analyses indicate that despite the similarities in outward manifestations, transcriptional and proteomic signatures in ALS motor neurons can vary significantly depending on the identity of the causal mutations.<\/jats:p>","DOI":"10.1093\/hmg\/ddz104","type":"journal-article","created":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T19:37:27Z","timestamp":1557862647000},"page":"2799-2810","source":"Crossref","is-referenced-by-count":32,"title":["Motor neurons from ALS patients with mutations in C9ORF72 and SOD1 exhibit distinct transcriptional landscapes"],"prefix":"10.1093","volume":"28","author":[{"given":"Ching-On","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Sciences Center (UTHealth), Houston, TX 77030, USA"},{"name":"Graduate Program in Biochemistry and Cell Biology, MD Anderson Cancer Center and UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3055-9265","authenticated-orcid":false,"given":"Kartik","family":"Venkatachalam","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Sciences Center (UTHealth), Houston, TX 77030, USA"},{"name":"Graduate Program in Biochemistry and Cell Biology, MD Anderson Cancer Center and UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,20]]},"reference":[{"key":"2019080902144447000_ref1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature20413","article-title":"Decoding ALS: from genes to mechanism","volume":"539","author":"Taylor","year":"2016","journal-title":"Nature"},{"key":"2019080902144447000_ref2","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.neuron.2013.07.033","article-title":"Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis","volume":"79","author":"Ling","year":"2013","journal-title":"Neuron"},{"key":"2019080902144447000_ref3","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS\u2013FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"2019080902144447000_ref4","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS","volume":"72","author":"DeJesus-Hernandez","year":"2011","journal-title":"Neuron"},{"key":"2019080902144447000_ref5","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1212\/WNL.0b013e3182661d14","article-title":"Hexanucleotide repeat expansions in C9ORF72 in the spectrum of motor neuron diseases","volume":"79","author":"van Rheenen","year":"2012","journal-title":"Neurology"},{"key":"2019080902144447000_ref6","doi-asserted-by":"crossref","first-page":"2232.e11","DOI":"10.1016\/j.neurobiolaging.2012.05.002","article-title":"A hexanucleotide repeat expansion in C9ORF72 causes familial and sporadic ALS in Taiwan","volume":"33","author":"Tsai","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"2019080902144447000_ref7","doi-asserted-by":"crossref","first-page":"1851.e1","DOI":"10.1016\/j.neurobiolaging.2012.02.021","article-title":"High frequency of the expanded C9ORF72 hexanucleotide repeat in familial and sporadic Greek ALS patients","volume":"33","author":"Mok","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"2019080902144447000_ref8","doi-asserted-by":"crossref","first-page":"1848.e15","DOI":"10.1016\/j.neurobiolaging.2012.02.011","article-title":"C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population","volume":"33","author":"Sabatelli","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"2019080902144447000_ref9","doi-asserted-by":"crossref","first-page":"145ra104","DOI":"10.1126\/scitranslmed.3004052","article-title":"Drug screening for ALS using patient-specific induced pluripotent stem cells","volume":"4","author":"Egawa","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"2019080902144447000_ref10","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.stem.2014.03.004","article-title":"Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1","volume":"14","author":"Kiskinis","year":"2014","journal-title":"Cell Stem Cell"},{"key":"2019080902144447000_ref11","doi-asserted-by":"crossref","first-page":"208ra149","DOI":"10.1126\/scitranslmed.3007529","article-title":"Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion","volume":"5","author":"Sareen","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"2019080902144447000_ref12","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.stemcr.2017.02.019","article-title":"Genetic correction of SOD1 mutant iPSCs reveals ERK and JNK activated AP1 as a driver of neurodegeneration in amyotrophic lateral sclerosis","volume":"8","author":"Bhinge","year":"2017","journal-title":"Stem Cell Reports"},{"key":"2019080902144447000_ref13","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/hmg\/ddp498","article-title":"Sporadic ALS has compartment-specific aberrant exon splicing and altered cell\u2013matrix adhesion biology","volume":"19","author":"Rabin","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"2019080902144447000_ref14","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13023-016-0531-y","article-title":"Gene expression profiles and protein\u2013protein interaction networks in amyotrophic lateral sclerosis patients with C9orf72 mutation","volume":"11","author":"Kotni","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"2019080902144447000_ref15","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1111\/nan.12148","article-title":"Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones","volume":"40","author":"Highley","year":"2014","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"2019080902144447000_ref16","doi-asserted-by":"crossref","first-page":"e37754","DOI":"10.7554\/eLife.37754","article-title":"Unexpected similarities between C9ORF72 and sporadic forms of ALS\/FTD suggest a common disease mechanism","volume":"7","author":"Conlon","year":"2018","journal-title":"Elife"},{"key":"2019080902144447000_ref17","doi-asserted-by":"crossref","first-page":"e53575","DOI":"10.1371\/journal.pone.0053575","article-title":"RNA-Seq profiling of spinal cord motor neurons from a presymptomatic SOD1 ALS mouse","volume":"8","author":"Bandyopadhyay","year":"2013","journal-title":"PLoS One"},{"key":"2019080902144447000_ref18","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1126\/science.8209258","article-title":"Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation","volume":"264","author":"Gurney","year":"1994","journal-title":"Science"},{"key":"2019080902144447000_ref19","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13029-017-0063-4","article-title":"DEApp: an interactive web interface for differential expression analysis of next generation sequence data","volume":"12","author":"Li","year":"2017","journal-title":"Source Code Biol. Med."},{"key":"2019080902144447000_ref20","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"2019080902144447000_ref21","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2019080902144447000_ref22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","article-title":"PGC-1\u03b1-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat. Genet."},{"key":"2019080902144447000_ref23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neuron.2005.06.005","article-title":"p53 mediates cellular dysfunction and behavioral abnormalities in Huntington\u2019s disease","volume":"47","author":"Bae","year":"2005","journal-title":"Neuron"},{"key":"2019080902144447000_ref24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuropharm.2018.11.019","article-title":"Amyloid-\u00df promotes neurotoxicity by Cdk5-induced p53 stabilization","volume":"146","author":"Lapresa","year":"2019","journal-title":"Neuropharmacology"},{"key":"2019080902144447000_ref25","doi-asserted-by":"crossref","first-page":"5371","DOI":"10.1172\/JCI70911","article-title":"Inhibition of mitochondrial fragmentation diminishes Huntington\u2019s disease\u2013associated neurodegeneration","volume":"123","author":"Guo","year":"2013","journal-title":"J. Clin. Invest."},{"key":"2019080902144447000_ref26","doi-asserted-by":"crossref","first-page":"e19105","DOI":"10.7554\/eLife.19105","article-title":"A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins","volume":"5","author":"Sung","year":"2016","journal-title":"Elife"},{"key":"2019080902144447000_ref27","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1126\/science.aar2663","article-title":"NUFIP1 is a ribosome receptor for starvation-induced ribophagy","volume":"360","author":"Wyant","year":"2018","journal-title":"Science (80-.)"},{"key":"2019080902144447000_ref28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41556-017-0007-x","article-title":"Systematic analysis of ribophagy in human cells reveals bystander flux during selective autophagy","volume":"20","author":"An","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"2019080902144447000_ref29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2019080902144447000_ref30","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"2019080902144447000_ref31","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1038\/nn.4065","article-title":"Distinct brain transcriptome profiles in C9orf72-associated and sporadic ALS","volume":"18","author":"Prudencio","year":"2015","journal-title":"Nat. Neurosci."},{"key":"2019080902144447000_ref32","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s00401-018-1870-7","article-title":"Transcriptome\u2013pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS","volume":"136","author":"Krach","year":"2018","journal-title":"Acta Neuropathol."},{"key":"2019080902144447000_ref33","doi-asserted-by":"crossref","first-page":"e17820","DOI":"10.7554\/eLife.17820","article-title":"The C9ORF72 GGGGCC expansion forms RNA G-quadruplex inclusions and sequesters hnRNP H to disrupt splicing in ALS brains","volume":"5","author":"Conlon","year":"2016","journal-title":"Elife"},{"key":"2019080902144447000_ref34","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s13238-017-0397-3","article-title":"CRISPR\/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs","volume":"8","author":"Wang","year":"2017","journal-title":"Protein Cell"},{"key":"2019080902144447000_ref35","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1083\/jcb.200205027","article-title":"A neurotoxic peripherin splice variant in a mouse model of ALS","volume":"160","author":"Robertson","year":"2003","journal-title":"J. Cell Biol."},{"key":"2019080902144447000_ref36","doi-asserted-by":"crossref","first-page":"45951","DOI":"10.1074\/jbc.M408139200","article-title":"A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis","volume":"279","author":"Gros-Louis","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2019080902144447000_ref37","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/j.1750-3639.2004.tb00066.x","article-title":"A pathogenic peripherin gene mutation in a patient with amyotrophic lateral sclerosis","volume":"14","author":"Leung","year":"2004","journal-title":"Brain Pathol."},{"key":"2019080902144447000_ref38","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1083\/jcb.147.3.531","article-title":"Late onset of motor neurons in mice overexpressing wild-type peripherin","volume":"147","author":"Beaulieu","year":"1999","journal-title":"J. Cell Biol."},{"key":"2019080902144447000_ref39","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1083\/jcb.200107058","article-title":"Apoptotic death of neurons exhibiting peripherin aggregates is mediated by the proinflammatory cytokine tumor necrosis factor-\u03b1","volume":"155","author":"Robertson","year":"2001","journal-title":"J. Cell Biol."},{"key":"2019080902144447000_ref40","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1523\/JNEUROSCI.3222-07.2008","article-title":"An aggregate-inducing peripherin isoform generated through intron retention is upregulated in amyotrophic lateral sclerosis and associated with disease pathology","volume":"28","author":"Xiao","year":"2008","journal-title":"J. Neurosci."},{"key":"2019080902144447000_ref41","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.neurobiolaging.2008.07.005","article-title":"Vesicle associated membrane protein B (VAPB) is decreased in ALS spinal cord","volume":"31","author":"Anagnostou","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"2019080902144447000_ref42","doi-asserted-by":"crossref","first-page":"E7701","DOI":"10.1073\/pnas.1611673113","article-title":"Two familial ALS proteins function in prevention\/repair of transcription-associated DNA damage","volume":"113","author":"Hill","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2019080902144447000_ref43","doi-asserted-by":"crossref","first-page":"175909141454447","DOI":"10.1177\/1759091414544472","article-title":"Functions of FUS\/TLS from DNA repair to stress response: implications for ALS","volume":"6","author":"Sama","year":"2014","journal-title":"ASN Neuro"},{"key":"2019080902144447000_ref44","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/nn.3514","article-title":"Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons","volume":"16","author":"Wang","year":"2013","journal-title":"Nat. Neurosci."},{"key":"2019080902144447000_ref45","doi-asserted-by":"crossref","first-page":"24731","DOI":"10.1074\/jbc.M113.497974","article-title":"The RNA-binding protein fused in sarcoma (FUS) functions downstream of poly (ADP-ribose) polymerase (PARP) in response to DNA damage","volume":"288","author":"Mastrocola","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2019080902144447000_ref46","doi-asserted-by":"crossref","first-page":"10493","DOI":"10.1016\/S0021-9258(19)70490-6","article-title":"ADP-ribosylation in mammalian cell ghosts. Dependence of poly (ADP-ribose) synthesis on strand breakage in DNA","volume":"255","author":"Benjamin","year":"1980","journal-title":"J. Biol. Chem."},{"key":"2019080902144447000_ref47","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/nar\/gkt835","article-title":"PARP-1 dependent recruitment of the amyotrophic lateral sclerosis-associated protein FUS\/TLS to sites of oxidative DNA damage","volume":"42","author":"Rulten","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2019080902144447000_ref48","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41467-017-02299-1","article-title":"Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation","volume":"9","author":"Naumann","year":"2018","journal-title":"Nat. Commun."},{"key":"2019080902144447000_ref49","doi-asserted-by":"crossref","first-page":"3683","DOI":"10.1038\/s41467-018-06111-6","article-title":"Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in amyotrophic lateral sclerosis","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"2019080902144447000_ref50","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.nbd.2017.02.004","article-title":"Neurobiology of axonal transport defects in motor neuron diseases: opportunities for translational research?","volume":"105","author":"De Vos","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"2019080902144447000_ref51","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nrc3556","article-title":"The DREAM complex: master coordinator of cell cycle-dependent gene expression","volume":"13","author":"Sadasivam","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"2019080902144447000_ref52","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.devcel.2017.11.008","article-title":"E2F\/DP prevents cell-cycle progression in endocycling fat body cells by suppressing dATM expression","volume":"43","author":"Guarner","year":"2017","journal-title":"Dev. Cell"},{"key":"2019080902144447000_ref53","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1101\/gad.949802","article-title":"E2F integrates cell cycle progression with DNA repair, replication, and G2\/M checkpoints","volume":"16","author":"Ren","year":"2002","journal-title":"Genes Dev."},{"key":"2019080902144447000_ref54","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0092-8674(02)00801-2","article-title":"E2F4\/5 and p107 as Smad cofactors linking the TGF\u03b2 receptor to c-myc repression","volume":"110","author":"Chen","year":"2002","journal-title":"Cell"},{"key":"2019080902144447000_ref55","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.1038\/onc.2008.165","article-title":"Rb\/E2F4 and Smad2\/3 link surviving to TGF-beta-induced apoptosis and tumor progression","volume":"27","author":"Yang","year":"2008","journal-title":"Oncogene"},{"key":"2019080902144447000_ref56","doi-asserted-by":"crossref","first-page":"3558","DOI":"10.1093\/nar\/gkq1313","article-title":"Wide-ranging functions of E2F4 in transcriptional activation and repression revealed by genome-wide analysis","volume":"39","author":"Lee","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2019080902144447000_ref57","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/ng1032","article-title":"Microarray data normalization and transformation","volume":"32","author":"Quackenbush","year":"2002","journal-title":"Nat. Genet."},{"key":"2019080902144447000_ref58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2202\/1544-6115.1027","article-title":"Linear models and empirical Bayes methods for assessing differential expression in microarray experiments","volume":"3","author":"Smyth","year":"2004","journal-title":"Stat. Appl. Genet. Mol. Biol."},{"key":"2019080902144447000_ref59","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1186\/1471-2105-9-542","article-title":"Corra: computational framework and tools for LC-MS discovery and targeted mass spectrometry-based proteomics","volume":"9","author":"Brusniak","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2019080902144447000_ref60","first-page":"3874","article-title":"Assessment and improvement of statistical tools for comparative proteomics analysis of sparse data sets with few experimental replicates","volume-title":"Journal of Proteome Research","author":"Schw\u00e4","year":"2013"},{"key":"2019080902144447000_ref61","doi-asserted-by":"crossref","first-page":"W300","DOI":"10.1093\/nar\/gkx444","article-title":"ProteoSign: an end-user online differential proteomics statistical analysis platform","volume":"45","author":"Efstathiou","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2019080902144447000_ref62","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12864-018-5362-x","article-title":"DEBrowser: interactive differential expression analysis and visualization tool for count data","volume":"20","author":"Kucukural","year":"2019","journal-title":"BMC Genomics"},{"key":"2019080902144447000_ref63","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1186\/1471-2105-12-436","article-title":"clusterMaker: a multi-algorithm clustering plugin for Cytoscape","volume":"12","author":"Morris","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2019080902144447000_ref64","doi-asserted-by":"crossref","first-page":"e13984","DOI":"10.1371\/journal.pone.0013984","article-title":"Enrichment map: a network-based method for gene-set enrichment visualization and interpretation","volume":"5","author":"Merico","year":"2010","journal-title":"PLoS One"},{"key":"2019080902144447000_ref65","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/0020-0190(89)90102-6","article-title":"An algorithm for drawing general undirected graphs","volume":"31","author":"Kamada","year":"1989","journal-title":"Inf. Process. Lett."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddz104\/28855770\/ddz104.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/28\/16\/2799\/29111676\/ddz104.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T01:05:22Z","timestamp":1663463122000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/28\/16\/2799\/5489939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,20]]},"references-count":65,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2019,5,20]]},"published-print":{"date-parts":[[2019,8,15]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddz104","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,8,15]]},"published":{"date-parts":[[2019,5,20]]}}}