{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T16:04:13Z","timestamp":1774022653808,"version":"3.50.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"23","funder":[{"name":"the Self Regional Healthcare Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>Motivation: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with clinical heterogeneity and a substantial polygenic component. High-throughput methods for ASD risk gene identification produce numerous candidate genes that are time-consuming and expensive to validate. Prioritization methods can identify high-confidence candidates. Previous ASD gene prioritization methods have focused on a priori knowledge, which excludes genes with little functional annotation or no protein product such as long non-coding RNAs (lncRNAs).<\/jats:p>\n               <jats:p>Results: We have developed a support vector machine (SVM) model, trained using brain developmental gene expression data, for the classification and prioritization of ASD risk genes. The selected feature model had a mean accuracy of 76.7%, mean specificity of 77.2% and mean sensitivity of 74.4%. Gene lists comprised of an ASD risk gene and adjacent genes were ranked using the model\u2019s decision function output. The known ASD risk genes were ranked on average in the 77.4th, 78.4th and 80.7th percentile for sets of 101, 201 and 401 genes respectively. Of 10,840 lncRNA genes, 63 were classified as ASD-associated candidates with a confidence greater than 0.95. Genes previously associated with brain development and neurodevelopmental disorders were prioritized highly within the lncRNA gene list.<\/jats:p>\n               <jats:p>Contact: \u00a0liangjw@clemson.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw498","type":"journal-article","created":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T00:52:41Z","timestamp":1470790361000},"page":"3611-3618","source":"Crossref","is-referenced-by-count":54,"title":["Support vector machine model of developmental brain gene expression data for prioritization of Autism risk gene candidates"],"prefix":"10.1093","volume":"32","author":[{"given":"S.","family":"Cogill","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,8,9]]},"reference":[{"key":"2023020114070705600_btw498-B1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/2040-2392-4-36","article-title":"SFARI Gene 2.0: A Community-Driven Knowledgebase for the Autism Spectrum Disorders (ASDs)","volume":"4","author":"Abrahams","year":"2013","journal-title":"Mol. Autism"},{"key":"2023020114070705600_btw498-B2","author":"American Psychiatric Association","year":"2012"},{"key":"2023020114070705600_btw498-B3","doi-asserted-by":"crossref","first-page":"4781","DOI":"10.1093\/hmg\/dds301","article-title":"Individual common variants exert weak effects on the risk for Autism Spectrum Disorders","volume":"21","author":"Anney","year":"2012","journal-title":"Hum. Mol. Genet"},{"key":"2023020114070705600_btw498-B4","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1038\/emboj.2013.245","article-title":"Transcriptome sequencing during mouse brain development identifies long non-coding RNAs functionally involved in neurogenic commitment","volume":"32","author":"Aprea","year":"2013","journal-title":"EMBO J"},{"key":"2023020114070705600_btw498-B5","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1016\/j.ridd.2010.04.009","article-title":"Psychiatric disorders in adolescents and adults with Autism and intellectual disability: a representative study in one county in Norway","volume":"31","author":"Bakken","year":"2010","journal-title":"Res. Dev. Disabil"},{"key":"2023020114070705600_btw498-B6","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1038\/emboj.2010.199","article-title":"A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression","volume":"29","author":"Bernard","year":"2010","journal-title":"EMBO J"},{"key":"2023020114070705600_btw498-B7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/2040-2392-5-11","article-title":"Behavioral signatures related to genetic disorders in autism","volume":"5","author":"Bruing","year":"2014","journal-title":"Mol. Autism"},{"key":"2023020114070705600_btw498-B8","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1613\/jair.953","article-title":"SMOTE: Synthetic Minority Over-sampling Technique","volume":"16","author":"Chawla","year":"2002","journal-title":"J. Artif. Intell. Res"},{"key":"2023020114070705600_btw498-B9","doi-asserted-by":"crossref","first-page":"e1121","DOI":"10.1542\/peds.2012-1525","article-title":"Large-scale use of the modified checklist for autism in low-risk toddlers","volume":"131","author":"Chlebowski","year":"2013","journal-title":"Pediatrics"},{"key":"2023020114070705600_btw498-B10","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/BF00994018","article-title":"Support-vector networks","volume":"20","author":"Cortes","year":"1995","journal-title":"Mach. Learn"},{"key":"2023020114070705600_btw498-B11","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nature13772","article-title":"Synaptic, transcriptional and chromatin genes disrupted in Autism","volume":"515","author":"De Rubeis","year":"2014","journal-title":"Nature"},{"key":"2023020114070705600_btw498-B12","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1101\/gr.132159.111","article-title":"The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression","volume":"22","author":"Derrien","year":"2012","journal-title":"Genome Res"},{"key":"2023020114070705600_btw498-B13","first-page":"1","article-title":"Prevalence of Autism Spectrum Disorder among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2010","volume":"63","author":"Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators and Centers for Disease Control and Prevention (CDC)","year":"2014","journal-title":"MMWR Surveil. Summ"},{"key":"2023020114070705600_btw498-B14","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/bib\/bbr059","article-title":"A review of statistical methods for prediction of proteolytic cleavage","volume":"13","author":"duVerle","year":"2012","journal-title":"Brief. Bioinf"},{"key":"2023020114070705600_btw498-B15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neuroimage.2009.08.024","article-title":"Investigating the predictive value of whole-brain structural MR scans in autism: a pattern classification approach","volume":"49","author":"Ecker","year":"2010","journal-title":"Neuroimage"},{"key":"2023020114070705600_btw498-B16","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S1474-4422(15)00050-2","article-title":"Neuroimaging in Autism spectrum disorder: brain structure and function across the lifespan","volume":"14","author":"Ecker","year":"2015","journal-title":"Lancet. NEURO"},{"key":"2023020114070705600_btw498-B17","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1101\/gr.117143.110","article-title":"Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis","volume":"21","author":"Erlich","year":"2011","journal-title":"Genome Res"},{"key":"2023020114070705600_btw498-B18","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ijdevneu.2015.04.003","article-title":"Autistic spectrum disorders: a review of clinical features, theories and diagnosis","volume":"43","author":"Fakhoury","year":"2015","journal-title":"Int. J. Dev. Neurosci"},{"key":"2023020114070705600_btw498-B19","first-page":"627","article-title":"Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation","volume":"4","author":"Hajian-Tilaki","year":"2013","journal-title":"Caspian J. Intern. Med"},{"key":"2023020114070705600_btw498-B20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1145\/1656274.1656278","article-title":"The WEKA data mining software: an update","volume":"11","author":"Hall","year":"2009","journal-title":"ACM SIGKDD Explorations Newslett"},{"key":"2023020114070705600_btw498-B21","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1101\/gr.135350.111","article-title":"GENCODE: the reference human genome annotation for the ENCODE project","volume":"22","author":"Harrow","year":"2012","journal-title":"Genome Res"},{"key":"2023020114070705600_btw498-B22","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nature11405","article-title":"An anatomically comprehensive atlas of the adult human brain transcriptome","volume":"489","author":"Hawrylycz","year":"2012","journal-title":"Nature"},{"key":"2023020114070705600_btw498-B23","first-page":"198363.","article-title":"A review of feature selection and feature extraction methods applied on microarray data","volume":"2015","author":"Hira","year":"2015","journal-title":"Adv. Bioinf"},{"key":"2023020114070705600_btw498-B24","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1192\/bjp.bp.108.060889","article-title":"Association between extreme autistic traits and intellectual disability: insights from a general population twin study","volume":"195","author":"Hoekstra","year":"2009","journal-title":"Br. J. Psychiatry"},{"key":"2023020114070705600_btw498-B25","volume-title":"Tech. Rep","author":"Hsu","year":"2003"},{"key":"2023020114070705600_btw498-B26","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.biopsych.2014.11.001","article-title":"Genetic epidemiology and insights into interactive genetic and environmental effects in autism spectrum disorders","volume":"77","author":"Kim","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"2023020114070705600_btw498-B27","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0004-3702(97)00043-X","article-title":"Wrappers for feature subset selection","volume":"97","author":"Kohavi","year":"1997","journal-title":"Artif. Intell"},{"key":"2023020114070705600_btw498-B28","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.csbj.2014.11.005","article-title":"Machine learning applications in cancer prognosis and prediction","volume":"13","author":"Kourou","year":"2014","journal-title":"Comput. Struct. Biotechnol. J"},{"key":"2023020114070705600_btw498-B54","first-page":"179","article-title":"Addressing the Curse of Imbalanced Training Sets: One Sided Selection","author":"Kubat","year":"1997"},{"key":"2023020114070705600_btw498-B29","first-page":"13","article-title":"Class-imbalanced classifiers for high-dimensional data","volume":"12","author":"Lin","year":"2012","journal-title":"Brief. Bioinform"},{"key":"2023020114070705600_btw498-B30","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.bbrc.2014.08.108","article-title":"Genomic and genetic aspects of autism spectrum disorder","volume":"452","author":"Liu","year":"2014","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2023020114070705600_btw498-B31","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/0005-2795(75)90109-9","article-title":"\u2018Comparison of the Predicted and Observed Secondary Structure of T4 Phage Lysozyme.\u2019","volume":"405","author":"Matthews","year":"1975","journal-title":"Biochim. Biophys. Acta"},{"key":"2023020114070705600_btw498-B32","doi-asserted-by":"crossref","first-page":"671.","DOI":"10.3389\/fnhum.2013.00671","article-title":"Evidence for dysregulation of axonal growth and guidance in the etiology of ASD","volume":"7","author":"McFadden","year":"2013","journal-title":"Front. Hum. Neurosci"},{"key":"2023020114070705600_btw498-B34","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nrg3253","article-title":"Computational tools for prioritizing candidate genes: boosting disease gene discovery","volume":"13","author":"Moreau","year":"2012","journal-title":"Nat. Rev. Genet"},{"key":"2023020114070705600_btw498-B35","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nature12943","article-title":"The evolution of lncRNA repertoires and expression patterns in tetrapods","volume":"505","author":"Necsulea","year":"2014","journal-title":"Nature"},{"key":"2023020114070705600_btw498-B36","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.cell.2013.10.031","article-title":"Integrative functional genomic analyses implicate specific molecular pathways and circuits in Autism","volume":"155","author":"Parikshak","year":"2013","journal-title":"Cell"},{"key":"2023020114070705600_btw498-B37","first-page":"2825","article-title":"Scikit-learn: machine learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res"},{"key":"2023020114070705600_btw498-B38","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nature09146","article-title":"Functional impact of global rare copy number variation in Autism spectrum disorders","volume":"466","author":"Pinto","year":"2010","journal-title":"Nature"},{"key":"2023020114070705600_btw498-B39","doi-asserted-by":"crossref","first-page":"i618","DOI":"10.1093\/bioinformatics\/btq396","article-title":"Candidate gene prioritization based on spatially mapped gene expression: an application to XLMR","volume":"26","author":"Piro","year":"2010","journal-title":"Bioinformatics"},{"key":"2023020114070705600_btw498-B40","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13229-015-0067-3","article-title":"The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study","volume":"7","author":"Retico","year":"2016","journal-title":"Mol. Autism"},{"key":"2023020114070705600_btw498-B41","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1093\/bioinformatics\/btm344","article-title":"A review of feature selection techniques in bioinformatics","volume":"23","author":"Saeys","year":"2007","journal-title":"Bioinformatics"},{"key":"2023020114070705600_btw498-B42","doi-asserted-by":"crossref","first-page":"e26049","DOI":"10.1371\/journal.pone.0026049","article-title":"Copy number variants in extended Autism spectrum disorder families reveal candidates potentially involved in Autism risk","volume":"6","author":"Salyakina","year":"2011","journal-title":"PloS One"},{"key":"2023020114070705600_btw498-B43","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.1523\/JNEUROSCI.5714-09.2010","article-title":"Longitudinal magnetic resonance imaging study of cortical development through early childhood in Autism","volume":"30","author":"Schumann","year":"2010","journal-title":"J. Neurosci"},{"key":"2023020114070705600_btw498-B44","doi-asserted-by":"crossref","first-page":"5194","DOI":"10.3390\/ijms16035194","article-title":"An overview of the prediction of protein DNA-binding sites","volume":"16","author":"Si","year":"2015","journal-title":"Int. J. Mol. Sci"},{"key":"2023020114070705600_btw498-B45","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.nicl.2015.04.008","article-title":"The Autism puzzle: diffuse but not pervasive neuroanatomical abnormalities in children with ASD","volume":"8","author":"Sussman","year":"2015","journal-title":"NeuroImage Clin"},{"key":"2023020114070705600_btw498-B46","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.ajhg.2010.04.011","article-title":"Haploinsufficiency of TAB2 causes congenital heart defects in humans","volume":"86","author":"Thienpont","year":"2010","journal-title":"Am. J. Hum. Genet"},{"key":"2023020114070705600_btw498-B47","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/978-1-4939-1115-8_12","article-title":"Machine learning-based methods for prediction of linear B-cell epitopes","volume":"1184","author":"Wang","year":"2014","journal-title":"Methods Mol. Biol"},{"key":"2023020114070705600_btw498-B48","doi-asserted-by":"crossref","first-page":"W243","DOI":"10.1093\/nar\/gkl298","article-title":"BindN: a web-based tool for efficient prediction of DNA and RNA binding sites in amino acid sequences","volume":"34","author":"Wang","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"2023020114070705600_btw498-B49","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.brainresbull.2013.06.001","article-title":"Roles of long noncoding RNAs in brain development, functional diversification and neurodegenerative diseases","volume":"97","author":"W\u00fcu","year":"2013","journal-title":"Brain Res. Bull"},{"key":"2023020114070705600_btw498-B50","doi-asserted-by":"crossref","first-page":"D1016","DOI":"10.1093\/nar\/gkr1145","article-title":"AutismKB: an evidence-based knowledgebase of Autism genetics","volume":"40","author":"Xu","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2023020114070705600_btw498-B51","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/bib\/5.4.328","article-title":"Biological applications of support vector machines","volume":"5","author":"Yang","year":"2004","journal-title":"Brief. Bioinf"},{"key":"2023020114070705600_btw498-B52","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s12031-012-9880-8","article-title":"Aberrant expression of long noncoding RNAs in Autistic brain","volume":"49","author":"Ziats","year":"2013","journal-title":"J. Mol. Neurosci"},{"key":"2023020114070705600_btw498-B53","first-page":"56","article-title":"A systematic review of molecular imaging (PET and SPECT) in Autism spectrum disorder: current state and future research opportunities","volume":"52","author":"Z\u00fcrcher","year":"2015","journal-title":"NeBiobehav. Rev"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/23\/3611\/49026979\/bioinformatics_32_23_3611.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/23\/3611\/49026979\/bioinformatics_32_23_3611.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T23:57:37Z","timestamp":1675295857000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/32\/23\/3611\/2525615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,9]]},"references-count":53,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2016,12,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btw498","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2016,12,1]]},"published":{"date-parts":[[2016,8,9]]}}}