{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T19:54:00Z","timestamp":1793476440072,"version":"4.5.0"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T00:00:00Z","timestamp":1637452800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T00:00:00Z","timestamp":1637452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"sandooq al watan","award":["SWARD-2019"],"award-info":[{"award-number":["SWARD-2019"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genomics"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In recent years, several hundred autism spectrum disorder (ASD) implicated genes have been discovered impacting a wide range of molecular pathways. However, the molecular underpinning of ASD, particularly from the point of view of \u2018brain to behaviour\u2019 pathogenic mechanisms, remains largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We undertook a study to investigate patterns of spatiotemporal and cell type expression of ASD-implicated genes by integrating large-scale brain single-cell transcriptomes (&gt;\u2009million cells) and de novo loss-of-function (LOF) ASD variants (impacting 852 genes from 40,122 cases).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified multiple single-cell clusters from three distinct developmental human brain regions (anterior cingulate cortex, middle temporal gyrus and primary visual cortex) that evidenced high evolutionary constraint through enrichment for brain critical exons and high pLI genes. These clusters also showed significant enrichment with ASD loss-of-function variant genes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20095.23\u2009\u00d7\u200910\n                      <jats:sup>\u201311<\/jats:sup>\n                      ) that are transcriptionally highly active in prenatal brain regions (visual cortex and dorsolateral prefrontal cortex). Mapping ASD de novo LOF variant genes into large-scale human and mouse brain single-cell transcriptome analysis demonstrate enrichment of such genes into neuronal subtypes and are also enriched for subtype of non-neuronal glial cell types (astrocyte,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20096.40\u2009\u00d7\u200910\n                      <jats:sup>\u201311<\/jats:sup>\n                      , oligodendrocyte,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20091.31\u2009\u00d7\u200910\n                      <jats:sup>\u201309<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Among the ASD genes enriched with pathogenic de novo LOF variants (i.e.\n                      <jats:italic>KANK1<\/jats:italic>\n                      ,\n                      <jats:italic>PLXNB1<\/jats:italic>\n                      ), a subgroup has restricted transcriptional regulation in non-neuronal cell types that are evolutionarily conserved. This association strongly suggests the involvement of subtype of non-neuronal glial cells in the pathogenesis of ASD and the need to explore other biological pathways for this disorder.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40246-021-00368-7","type":"journal-article","created":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T16:05:42Z","timestamp":1637510742000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Single-cell transcriptome identifies molecular subtype of autism spectrum disorder impacted by de novo loss-of-function variants regulating glial cells"],"prefix":"10.1186","volume":"15","author":[{"given":"Nasna","family":"Nassir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Bankapur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bisan","family":"Samara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awab","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim M.","family":"Inuwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Zarrei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Ali","family":"Safizadeh Shabestari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar","family":"AlBanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Howe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakhrom K.","family":"Berdiev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Woodbury-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,21]]},"reference":[{"issue":"17","key":"368_CR1","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1001\/jama.2014.4144","volume":"311","author":"S Sandin","year":"2014","unstructured":"Sandin S, et al. The familial risk of autism. JAMA. 2014;311(17):1770\u20137.","journal-title":"JAMA"},{"issue":"1","key":"368_CR2","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1017\/S0033291700028099","volume":"25","author":"A Bailey","year":"1995","unstructured":"Bailey A, et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med. 1995;25(1):63\u201377.","journal-title":"Psychol Med"},{"issue":"4","key":"368_CR3","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1111\/j.1469-7610.1977.tb00443.x","volume":"18","author":"S Folstein","year":"1977","unstructured":"Folstein S, Rutter M. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry. 1977;18(4):297\u2013321.","journal-title":"J Child Psychol Psychiatry"},{"issue":"1","key":"368_CR4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41572-019-0138-4","volume":"6","author":"C Lord","year":"2020","unstructured":"Lord C, et al. Autism spectrum disorder. Nat Rev Dis Primers. 2020;6(1):5.","journal-title":"Nat Rev Dis Primers"},{"issue":"4","key":"368_CR5","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1002\/ajmg.b.32306","volume":"168B","author":"Y Liu","year":"2015","unstructured":"Liu Y, et al. Rare de novo deletion of metabotropic glutamate receptor 7 (GRM7) gene in a patient with autism spectrum disorder. Am J Med Genet B Neuropsychiatr Genet. 2015;168B(4):258\u201364.","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"issue":"3","key":"368_CR6","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.cell.2019.12.036","volume":"180","author":"FK Satterstrom","year":"2020","unstructured":"Satterstrom FK, et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell. 2020;180(3):568\u201384.","journal-title":"Cell"},{"issue":"R1","key":"368_CR7","doi-asserted-by":"publisher","first-page":"R24","DOI":"10.1093\/hmg\/ddv273","volume":"24","author":"S De Rubeis","year":"2015","unstructured":"De Rubeis S, Buxbaum JD. Genetics and genomics of autism spectrum disorder: embracing complexity. Hum Mol Genet. 2015;24(R1):R24-31.","journal-title":"Hum Mol Genet"},{"key":"368_CR8","doi-asserted-by":"publisher","first-page":"774","DOI":"10.15252\/msb.20145487","volume":"10","author":"J Li","year":"2014","unstructured":"Li J, et al. Integrated systems analysis reveals a molecular network underlying autism spectrum disorders. Mol Syst Biol. 2014;10:774.","journal-title":"Mol Syst Biol"},{"issue":"5","key":"368_CR9","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1016\/j.cell.2013.10.031","volume":"155","author":"NN Parikshak","year":"2013","unstructured":"Parikshak NN, et al. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell. 2013;155(5):1008\u201321.","journal-title":"Cell"},{"key":"368_CR10","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41746-019-0191-0","volume":"2","author":"M Uddin","year":"2019","unstructured":"Uddin M, Wang Y, Woodbury-Smith M. Artificial intelligence for precision medicine in neurodevelopmental disorders. NPJ Digit Med. 2019;2:112.","journal-title":"NPJ Digit Med"},{"issue":"3","key":"368_CR11","doi-asserted-by":"publisher","first-page":"e1002556","DOI":"10.1371\/journal.pgen.1002556","volume":"8","author":"E Ben-David","year":"2012","unstructured":"Ben-David E, Shifman S. Networks of neuronal genes affected by common and rare variants in autism spectrum disorders. PLoS Genet. 2012;8(3):e1002556.","journal-title":"PLoS Genet"},{"issue":"5","key":"368_CR12","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.cell.2013.10.020","volume":"155","author":"AJ Willsey","year":"2013","unstructured":"Willsey AJ, et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell. 2013;155(5):997\u20131007.","journal-title":"Cell"},{"issue":"4","key":"368_CR13","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1007\/s12031-015-0641-3","volume":"57","author":"A Mahfouz","year":"2015","unstructured":"Mahfouz A, et al. Shared pathways among autism candidate genes determined by co-expression network analysis of the developing human brain transcriptome. J Mol Neurosci. 2015;57(4):580\u201394.","journal-title":"J Mol Neurosci"},{"issue":"6","key":"368_CR14","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1101\/gr.254987.119","volume":"30","author":"K Pang","year":"2020","unstructured":"Pang K, et al. Coexpression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders. Genome Res. 2020;30(6):835\u201348.","journal-title":"Genome Res"},{"issue":"1","key":"368_CR15","doi-asserted-by":"publisher","first-page":"107489","DOI":"10.1016\/j.celrep.2020.03.053","volume":"31","author":"DM Werling","year":"2020","unstructured":"Werling DM, et al. Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex. Cell Rep. 2020;31(1):107489.","journal-title":"Cell Rep"},{"issue":"9","key":"368_CR16","doi-asserted-by":"publisher","first-page":"109631","DOI":"10.1016\/j.celrep.2021.109631","volume":"36","author":"KK Chau","year":"2021","unstructured":"Chau KK, et al. Full-length isoform transcriptome of the developing human brain provides further insights into autism. Cell Rep. 2021;36(9):109631.","journal-title":"Cell Rep"},{"key":"368_CR17","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3389\/fncel.2016.00263","volume":"10","author":"YC Lin","year":"2016","unstructured":"Lin YC, et al. A subset of autism-associated genes regulate the structural stability of neurons. Front Cell Neurosci. 2016;10:263.","journal-title":"Front Cell Neurosci"},{"issue":"1","key":"368_CR18","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1038\/s41467-020-14697-z","volume":"11","author":"K Matsumura","year":"2020","unstructured":"Matsumura K, et al. Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes. Nat Commun. 2020;11(1):859.","journal-title":"Nat Commun"},{"issue":"6","key":"368_CR19","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1007\/s00401-018-1850-y","volume":"135","author":"BM Verheijen","year":"2018","unstructured":"Verheijen BM, Vermulst M, van Leeuwen FW. Somatic mutations in neurons during aging and neurodegeneration. Acta Neuropathol. 2018;135(6):811\u201326.","journal-title":"Acta Neuropathol"},{"issue":"7416","key":"368_CR20","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/nature11405","volume":"489","author":"MJ Hawrylycz","year":"2012","unstructured":"Hawrylycz MJ, et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature. 2012;489(7416):391\u20139.","journal-title":"Nature"},{"key":"368_CR21","doi-asserted-by":"publisher","first-page":"406","DOI":"10.3389\/fgene.2018.00406","volume":"9","author":"A Alonso-Gonzalez","year":"2018","unstructured":"Alonso-Gonzalez A, Rodriguez-Fontenla C, Carracedo A. De novo mutations (DNMs) in autism spectrum disorder (ASD): pathway and network analysis. Front Genet. 2018;9:406.","journal-title":"Front Genet"},{"issue":"6","key":"368_CR22","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1097\/MOP.0000000000000278","volume":"27","author":"EB Robinson","year":"2015","unstructured":"Robinson EB, Neale BM, Hyman SE. Genetic research in autism spectrum disorders. Curr Opin Pediatr. 2015;27(6):685\u201391.","journal-title":"Curr Opin Pediatr"},{"issue":"7","key":"368_CR23","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart T, et al. Comprehensive Integration of Single-Cell Data. Cell. 2019;177(7):1888-1902 e21.","journal-title":"Cell"},{"issue":"2","key":"368_CR24","doi-asserted-by":"publisher","first-page":"e31505","DOI":"10.1371\/journal.pone.0031505","volume":"7","author":"Z Fang","year":"2012","unstructured":"Fang Z, Du R, Cui X. Uniform approximation is more appropriate for Wilcoxon Rank-Sum Test in gene set analysis. PLoS ONE. 2012;7(2):e31505.","journal-title":"PLoS ONE"},{"issue":"6","key":"368_CR25","doi-asserted-by":"publisher","first-page":"540","DOI":"10.4097\/kjae.2015.68.6.540","volume":"68","author":"TK Kim","year":"2015","unstructured":"Kim TK. T test as a parametric statistic. Korean J Anesthesiol. 2015;68(6):540\u20136.","journal-title":"Korean J Anesthesiol"},{"issue":"4","key":"368_CR26","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1093\/bioinformatics\/bts714","volume":"29","author":"A McDavid","year":"2013","unstructured":"McDavid A, et al. Data exploration, quality control and testing in single-cell qPCR-based gene expression experiments. Bioinformatics. 2013;29(4):461\u20137.","journal-title":"Bioinformatics"},{"key":"368_CR27","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1186\/s13059-015-0844-5","volume":"16","author":"G Finak","year":"2015","unstructured":"Finak G, et al. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 2015;16:278.","journal-title":"Genome Biol"},{"issue":"7","key":"368_CR28","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1038\/ng.2980","volume":"46","author":"M Uddin","year":"2014","unstructured":"Uddin M, et al. Brain-expressed exons under purifying selection are enriched for de novo mutations in autism spectrum disorder. Nat Genet. 2014;46(7):742\u20137.","journal-title":"Nat Genet"},{"issue":"7370","key":"368_CR29","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/nature10523","volume":"478","author":"HJ Kang","year":"2011","unstructured":"Kang HJ, et al. Spatio-temporal transcriptome of the human brain. Nature. 2011;478(7370):483\u20139.","journal-title":"Nature"},{"issue":"7616","key":"368_CR30","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nature19057","volume":"536","author":"M Lek","year":"2016","unstructured":"Lek M, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536(7616):285\u201391.","journal-title":"Nature"},{"issue":"5","key":"368_CR31","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1038\/s41588-019-0383-1","volume":"51","author":"ZL Fuller","year":"2019","unstructured":"Fuller ZL, et al. Measuring intolerance to mutation in human genetics. Nat Genet. 2019;51(5):772\u20136.","journal-title":"Nat Genet"},{"issue":"7539","key":"368_CR32","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/nature14221","volume":"518","author":"P Polak","year":"2015","unstructured":"Polak P, et al. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature. 2015;518(7539):360\u20134.","journal-title":"Nature"},{"key":"368_CR33","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1038\/ncomms1982","volume":"3","author":"YH Woo","year":"2012","unstructured":"Woo YH, Li WH. DNA replication timing and selection shape the landscape of nucleotide variation in cancer genomes. Nat Commun. 2012;3:1004.","journal-title":"Nat Commun"},{"issue":"9","key":"368_CR34","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1038\/nn.4598","volume":"20","author":"ET Lim","year":"2017","unstructured":"Lim ET, et al. Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Nat Neurosci. 2017;20(9):1217\u201324.","journal-title":"Nat Neurosci"},{"issue":"7526","key":"368_CR35","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature13908","volume":"515","author":"I Iossifov","year":"2014","unstructured":"Iossifov I, et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014;515(7526):216\u201321.","journal-title":"Nature"},{"key":"368_CR36","doi-asserted-by":"crossref","unstructured":"Franzen O, Gan LM, Bjorkegren JLM. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database (Oxford), 2019. 2019.","DOI":"10.1093\/database\/baz046"},{"issue":"6441","key":"368_CR37","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1126\/science.aav8130","volume":"364","author":"D Velmeshev","year":"2019","unstructured":"Velmeshev D, et al. Single-cell genomics identifies cell type-specific molecular changes in autism. Science. 2019;364(6441):685\u20139.","journal-title":"Science"},{"issue":"1","key":"368_CR38","doi-asserted-by":"publisher","first-page":"8868","DOI":"10.1038\/s41598-018-27293-5","volume":"8","author":"AT McKenzie","year":"2018","unstructured":"McKenzie AT, et al. Brain cell type specific gene expression and co-expression network architectures. Sci Rep. 2018;8(1):8868.","journal-title":"Sci Rep"},{"issue":"1","key":"368_CR39","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1186\/s12864-018-4772-0","volume":"19","author":"K Street","year":"2018","unstructured":"Street K, et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics. 2018;19(1):477.","journal-title":"BMC Genomics"},{"issue":"23","key":"368_CR40","doi-asserted-by":"publisher","first-page":"7285","DOI":"10.1073\/pnas.1507125112","volume":"112","author":"S Darmanis","year":"2015","unstructured":"Darmanis S, et al. A survey of human brain transcriptome diversity at the single cell level. Proc Natl Acad Sci USA. 2015;112(23):7285\u201390.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"36","key":"368_CR41","doi-asserted-by":"publisher","first-page":"11929","DOI":"10.1523\/JNEUROSCI.1860-14.2014","volume":"34","author":"Y Zhang","year":"2014","unstructured":"Zhang Y, et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014;34(36):11929\u201347.","journal-title":"J Neurosci"},{"issue":"3","key":"368_CR42","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.biopsych.2016.02.021","volume":"81","author":"AS Reddy","year":"2017","unstructured":"Reddy AS, et al. A comprehensive analysis of cell type-specific nuclear RNA from neurons and glia of the brain. Biol Psychiatry. 2017;81(3):252\u201364.","journal-title":"Biol Psychiatry"},{"issue":"1","key":"368_CR43","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.neuron.2015.11.013","volume":"89","author":"Y Zhang","year":"2016","unstructured":"Zhang Y, et al. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron. 2016;89(1):37\u201353.","journal-title":"Neuron"},{"key":"368_CR44","doi-asserted-by":"crossref","unstructured":"Cao J, et al.,A human cell atlas of fetal gene expression. Science. 2020. 370(6518).","DOI":"10.1126\/science.aba7721"},{"key":"368_CR45","doi-asserted-by":"publisher","first-page":"D1046","DOI":"10.1093\/nar\/gkaa1070","volume":"49","author":"J Navarro Gonzalez","year":"2020","unstructured":"Navarro Gonzalez J, et al. The UCSC Genome Browser database: 2021 update. Nucleic Acids Res. 2020;49:D1046.","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"368_CR46","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nn.4216","volume":"19","author":"B Tasic","year":"2016","unstructured":"Tasic B, et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat Neurosci. 2016;19(2):335\u201346.","journal-title":"Nat Neurosci"},{"key":"368_CR47","doi-asserted-by":"publisher","first-page":"205","DOI":"10.3389\/fcell.2019.00205","volume":"7","author":"YH Pan","year":"2019","unstructured":"Pan YH, Wu N, Yuan XB. Toward a better understanding of neuronal migration deficits in autism spectrum disorders. Front Cell Dev Biol. 2019;7:205.","journal-title":"Front Cell Dev Biol"},{"issue":"3","key":"368_CR48","doi-asserted-by":"publisher","first-page":"133","DOI":"10.5607\/en.2013.22.3.133","volume":"22","author":"KM Lee","year":"2013","unstructured":"Lee KM, Hwang SK, Lee JA. Neuronal autophagy and neurodevelopmental disorders. Exp Neurobiol. 2013;22(3):133\u201342.","journal-title":"Exp Neurobiol"},{"issue":"5","key":"368_CR49","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.tins.2020.03.005","volume":"43","author":"E Courchesne","year":"2020","unstructured":"Courchesne E, Gazestani VH, Lewis NE. Prenatal origins of ASD: the when, what, and how of ASD development. Trends Neurosci. 2020;43(5):326\u201342.","journal-title":"Trends Neurosci"},{"issue":"18","key":"368_CR50","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1001\/jama.2011.1638","volume":"306","author":"E Courchesne","year":"2011","unstructured":"Courchesne E, et al. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011;306(18):2001\u201310.","journal-title":"JAMA"},{"issue":"5","key":"368_CR51","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1016\/j.cortex.2012.05.022","volume":"49","author":"AK Barbey","year":"2013","unstructured":"Barbey AK, Koenigs M, Grafman J. Dorsolateral prefrontal contributions to human working memory. Cortex. 2013;49(5):1195\u2013205.","journal-title":"Cortex"},{"issue":"1","key":"368_CR52","doi-asserted-by":"publisher","first-page":"3816","DOI":"10.1038\/s41467-019-11764-y","volume":"10","author":"A Turnbull","year":"2019","unstructured":"Turnbull A, et al. Left dorsolateral prefrontal cortex supports context-dependent prioritisation of off-task thought. Nat Commun. 2019;10(1):3816.","journal-title":"Nat Commun"},{"issue":"1","key":"368_CR53","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s11689-019-9266-0","volume":"11","author":"S Aoki","year":"2019","unstructured":"Aoki S, et al. Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study. J Neurodev Disord. 2019;11(1):9.","journal-title":"J Neurodev Disord"},{"key":"368_CR54","doi-asserted-by":"publisher","first-page":"627","DOI":"10.3389\/fnins.2017.00627","volume":"11","author":"T Yamasaki","year":"2017","unstructured":"Yamasaki T, et al. Connectopathy in Autism Spectrum Disorders: a review of evidence from visual evoked potentials and diffusion magnetic resonance imaging. Front Neurosci. 2017;11:627.","journal-title":"Front Neurosci"},{"key":"368_CR55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neubiorev.2013.12.001","volume":"39","author":"EJ Jones","year":"2014","unstructured":"Jones EJ, et al. Developmental pathways to autism: a review of prospective studies of infants at risk. Neurosci Biobehav Rev. 2014;39:1\u201333.","journal-title":"Neurosci Biobehav Rev"},{"issue":"4","key":"368_CR56","doi-asserted-by":"publisher","first-page":"e0175433","DOI":"10.1371\/journal.pone.0175433","volume":"12","author":"JG Gehricke","year":"2017","unstructured":"Gehricke JG, et al. The brain anatomy of attention-deficit\/hyperactivity disorder in young adults - a magnetic resonance imaging study. PLoS ONE. 2017;12(4):e0175433.","journal-title":"PLoS ONE"},{"key":"368_CR57","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/B978-0-444-53860-4.00009-X","volume":"195","author":"K Teffer","year":"2012","unstructured":"Teffer K, Semendeferi K. Human prefrontal cortex: evolution, development, and pathology. Prog Brain Res. 2012;195:191\u2013218.","journal-title":"Prog Brain Res"},{"key":"368_CR58","doi-asserted-by":"publisher","first-page":"149","DOI":"10.3389\/fncel.2015.00149","volume":"9","author":"JA Brandao","year":"2015","unstructured":"Brandao JA, Romcy-Pereira RN. Interplay of environmental signals and progenitor diversity on fate specification of cortical GABAergic neurons. Front Cell Neurosci. 2015;9:149.","journal-title":"Front Cell Neurosci"},{"issue":"Pt 21","key":"368_CR59","doi-asserted-by":"publisher","first-page":"4381","DOI":"10.1242\/jcs.03242","volume":"119","author":"M Simons","year":"2006","unstructured":"Simons M, Trajkovic K. Neuron-glia communication in the control of oligodendrocyte function and myelin biogenesis. J Cell Sci. 2006;119(Pt 21):4381\u20139.","journal-title":"J Cell Sci"},{"key":"368_CR60","doi-asserted-by":"publisher","first-page":"76","DOI":"10.3389\/fncel.2015.00076","volume":"9","author":"C Schitine","year":"2015","unstructured":"Schitine C, et al. Astrocyte heterogeneity in the brain: from development to disease. Front Cell Neurosci. 2015;9:76.","journal-title":"Front Cell Neurosci"},{"issue":"1","key":"368_CR61","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/j.1471-4159.2012.07664.x","volume":"121","author":"V Parpura","year":"2012","unstructured":"Parpura V, et al. Glial cells in (patho)physiology. J Neurochem. 2012;121(1):4\u201327.","journal-title":"J Neurochem"},{"issue":"22","key":"368_CR62","doi-asserted-by":"publisher","first-page":"3805","DOI":"10.1242\/dev.129304","volume":"142","author":"JB Zuchero","year":"2015","unstructured":"Zuchero JB, Barres BA. Glia in mammalian development and disease. Development. 2015;142(22):3805\u20139.","journal-title":"Development"},{"issue":"3","key":"368_CR63","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.neuron.2008.10.013","volume":"60","author":"BA Barres","year":"2008","unstructured":"Barres BA. The mystery and magic of glia: a perspective on their roles in health and disease. Neuron. 2008;60(3):430\u201340.","journal-title":"Neuron"},{"key":"368_CR64","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.conb.2014.03.005","volume":"27","author":"SA Sloan","year":"2014","unstructured":"Sloan SA, Barres BA. Mechanisms of astrocyte development and their contributions to neurodevelopmental disorders. Curr Opin Neurobiol. 2014;27:75\u201381.","journal-title":"Curr Opin Neurobiol"},{"issue":"9","key":"368_CR65","doi-asserted-by":"publisher","first-page":"a020370","DOI":"10.1101\/cshperspect.a020370","volume":"7","author":"WS Chung","year":"2015","unstructured":"Chung WS, Allen NJ, Eroglu C. Astrocytes control synapse formation, function, and elimination. Cold Spring Harb Perspect Biol. 2015;7(9):a020370.","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"368_CR66","doi-asserted-by":"crossref","unstructured":"Cope EC, et al. Immature neurons and radial glia, but not astrocytes or microglia, are altered in adult Cntnap2 and Shank3 mice, models of autism. eNeuro. 2016. 3(5).","DOI":"10.1523\/ENEURO.0196-16.2016"},{"key":"368_CR67","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.brainres.2012.03.036","volume":"1456","author":"JT Morgan","year":"2012","unstructured":"Morgan JT, et al. Abnormal microglial-neuronal spatial organization in the dorsolateral prefrontal cortex in autism. Brain Res. 2012;1456:72\u201381.","journal-title":"Brain Res"},{"issue":"4","key":"368_CR68","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.biopsych.2010.05.024","volume":"68","author":"JT Morgan","year":"2010","unstructured":"Morgan JT, et al. Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry. 2010;68(4):368\u201376.","journal-title":"Biol Psychiatry"},{"issue":"1","key":"368_CR69","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/ana.20315","volume":"57","author":"DL Vargas","year":"2005","unstructured":"Vargas DL, et al. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67\u201381.","journal-title":"Ann Neurol"},{"issue":"1","key":"368_CR70","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1001\/jamapsychiatry.2013.272","volume":"70","author":"K Suzuki","year":"2013","unstructured":"Suzuki K, et al. Microglial activation in young adults with autism spectrum disorder. JAMA Psychiat. 2013;70(1):49\u201358.","journal-title":"JAMA Psychiat"},{"issue":"1","key":"368_CR71","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1038\/s41467-020-15530-3","volume":"11","author":"ZX Xu","year":"2020","unstructured":"Xu ZX, et al. Elevated protein synthesis in microglia causes autism-like synaptic and behavioral aberrations. Nat Commun. 2020;11(1):1797.","journal-title":"Nat Commun"},{"issue":"1","key":"368_CR72","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.neuron.2009.09.001","volume":"64","author":"LM Boulanger","year":"2009","unstructured":"Boulanger LM. Immune proteins in brain development and synaptic plasticity. Neuron. 2009;64(1):93\u2013109.","journal-title":"Neuron"},{"key":"368_CR73","doi-asserted-by":"publisher","first-page":"738","DOI":"10.3389\/fnhum.2013.00738","volume":"7","author":"I Voineagu","year":"2013","unstructured":"Voineagu I, Eapen V. Converging pathways in autism spectrum disorders: interplay between synaptic dysfunction and immune responses. Front Hum Neurosci. 2013;7:738.","journal-title":"Front Hum Neurosci"},{"issue":"6","key":"368_CR74","doi-asserted-by":"publisher","first-page":"4507","DOI":"10.1007\/s12035-016-9961-8","volume":"54","author":"X Liu","year":"2017","unstructured":"Liu X, et al. Idiopathic autism: cellular and molecular phenotypes in pluripotent stem cell-derived neurons. Mol Neurobiol. 2017;54(6):4507\u201323.","journal-title":"Mol Neurobiol"},{"issue":"6226","key":"368_CR75","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1126\/science.aaa1934","volume":"347","author":"A Zeisel","year":"2015","unstructured":"Zeisel A, et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science. 2015;347(6226):1138\u201342.","journal-title":"Science"},{"key":"368_CR76","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.mcn.2018.06.008","volume":"92","author":"JE McDermott","year":"2018","unstructured":"McDermott JE, Goldblatt D, Paradis S. Class 4 Semaphorins and Plexin-B receptors regulate GABAergic and glutamatergic synapse development in the mammalian hippocampus. Mol Cell Neurosci. 2018;92:50\u201366.","journal-title":"Mol Cell Neurosci"},{"issue":"7528","key":"368_CR77","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/nature14011","volume":"515","author":"RS Herbst","year":"2014","unstructured":"Herbst RS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563\u20137.","journal-title":"Nature"},{"issue":"26","key":"368_CR78","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.1056\/NEJMoa1103782","volume":"364","author":"PB Chapman","year":"2011","unstructured":"Chapman PB, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507\u201316.","journal-title":"N Engl J Med"},{"issue":"5897","key":"368_CR79","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1126\/science.1164382","volume":"321","author":"DW Parsons","year":"2008","unstructured":"Parsons DW, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807\u201312.","journal-title":"Science"},{"issue":"11","key":"368_CR80","doi-asserted-by":"publisher","first-page":"5499","DOI":"10.1021\/acs.jctc.8b00652","volume":"14","author":"H Zhou","year":"2018","unstructured":"Zhou H, Wang F, Tao P. t-Distributed stochastic neighbor embedding method with the least information loss for macromolecular simulations. J Chem Theory Comput. 2018;14(11):5499\u2013510.","journal-title":"J Chem Theory Comput"},{"issue":"2","key":"368_CR81","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.cell.2011.06.013","volume":"146","author":"JC Darnell","year":"2011","unstructured":"Darnell JC, et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell. 2011;146(2):247\u201361.","journal-title":"Cell"},{"key":"368_CR82","doi-asserted-by":"crossref","unstructured":"Sunkin SM, et al. Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system. Nucleic Acids Res. 2013;41(Database issue), D996-D1008.","DOI":"10.1093\/nar\/gks1042"},{"issue":"2","key":"368_CR83","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1093\/bioinformatics\/btq643","volume":"27","author":"L Habegger","year":"2011","unstructured":"Habegger L, et al. RSEQtools: a modular framework to analyze RNA-Seq data using compact, anonymized data summaries. Bioinformatics. 2011;27(2):281\u20133.","journal-title":"Bioinformatics"},{"issue":"7","key":"368_CR84","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/nmeth.1226","volume":"5","author":"A Mortazavi","year":"2008","unstructured":"Mortazavi A, et al. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods. 2008;5(7):621\u20138.","journal-title":"Nat Methods"},{"issue":"43","key":"368_CR85","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102(43):15545\u201350.","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Human Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40246-021-00368-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40246-021-00368-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40246-021-00368-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T02:06:10Z","timestamp":1667009170000},"score":1,"resource":{"primary":{"URL":"https:\/\/humgenomics.biomedcentral.com\/articles\/10.1186\/s40246-021-00368-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,21]]},"references-count":85,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["368"],"URL":"https:\/\/doi.org\/10.1186\/s40246-021-00368-7","relation":{},"ISSN":["1479-7364"],"issn-type":[{"value":"1479-7364","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,21]]},"assertion":[{"value":"30 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study received approval from the institutional review board of the Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU-IRB-2017-004).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"68"}}