{"id":149438,"date":"2022-11-04T03:22:19","date_gmt":"2022-11-04T08:22:19","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2022\/11\/broad-transcriptomic-dysregulation-occurs-across-the-cerebral-cortex-in-asd"},"modified":"2022-11-04T03:22:19","modified_gmt":"2022-11-04T08:22:19","slug":"broad-transcriptomic-dysregulation-occurs-across-the-cerebral-cortex-in-asd","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2022\/11\/broad-transcriptomic-dysregulation-occurs-across-the-cerebral-cortex-in-asd","title":{"rendered":"Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/broad-transcriptomic-dysregulation-occurs-across-the-cerebral-cortex-in-asd.jpg\"><\/a><\/p>\n<p>ARI gene groups (ARI downregulated genes, those highly expressed in BA17 and BA39\/40 relative to other regions in controls; ARI upregulated genes, those expressed at low level in BA17 and BA39\/40 relative to other regions in controls) were created through taking the union (without duplicates) across all ten identified ASD-attenuated regional comparisons, and sorting genes into the two groups based on gene-expression profiles across regions. The details of this process are described in the <a data-track=\"click\" data-track-label=\"link\" data-track-action=\"supplementary material anchor\" href=\"https:\/\/www.nature.com\/articles\/s41586-022-05377-7#MOESM1\">Supplementary Methods<\/a>, along with functional annotation procedures.<\/p>\n<p>Standard workflows using WGCNA<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 17\" title=\"Langfelder, P. & Horvath, S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinf. 9,559 (2008).\" href=\"https:\/\/www.nature.com\/articles\/s41586-022-05377-7#ref-CR17\" id=\"ref-link-section-d12359870e2111\">17<\/a><\/sup> were followed as previously described in Parikshak <i>et al.<\/i><sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 5\" title=\"Parikshak, N. N. et al. Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism. Nature 540423&ndash;427 (2016).\" href=\"https:\/\/www.nature.com\/articles\/s41586-022-05377-7#ref-CR5\" id=\"ref-link-section-d12359870e2115\">5<\/a><\/sup> and Gandal <i>et al.<\/i><sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\" title=\"Gandal, M. J. et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science 362, eaat8127 (2018).\" href=\"https:\/\/www.nature.com\/articles\/s41586-022-05377-7#ref-CR1\" id=\"ref-link-section-d12359870e2119\">1<\/a><\/sup> (with minor modifications) to identify gene and transcript co-expression modules. Details regarding network formation, module identification, and module functional characterization are described in the <a data-track=\"click\" data-track-label=\"link\" data-track-action=\"supplementary material anchor\" href=\"https:\/\/www.nature.com\/articles\/s41586-022-05377-7#MOESM1\">Supplementary Methods<\/a>.<\/p>\n<p>Frozen brain samples were placed on dry ice in a dehydrated dissection chamber to reduce degradation effects from sample thawing and\/or humidity. Approximately 50 mg of cortex was sectioned, ensuring specific grey matter\u2013white matter boundary. The tissue section was homogenized in RNase-free conditions with a light detergent briefly on ice using a dounce homogenizer, filtered through a 40-\u03bcM filter and centrifuged at 1,000 <i>g<\/i> for 8 min at 4 \u00b0C. The pelleted nuclei were then filtered through a two-part micro gradient (30%\/50%) for 20 min at 4 \u00b0C. Clean nuclei were pelleted away from debris. The nuclei were washed two more times with PBS\/1%BSA\/RNase and spun down at 500 <i>g<\/i> for 5 min. Cells were inspected for quality (shape, colour and membrane integrity) and counted on a Countess II instrument. They were then loaded onto the 10X Genomics platform to isolate single nuclei and generate libraries for RNA sequencing on the NovaS4 or NovaS2 Illumina machines.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>ARI gene groups (ARI downregulated genes, those highly expressed in BA17 and BA39\/40 relative to other regions in controls; ARI upregulated genes, those expressed at low level in BA17 and BA39\/40 relative to other regions in controls) were created through taking the union (without duplicates) across all ten identified ASD-attenuated regional comparisons, and sorting genes [\u2026]<\/p>\n","protected":false},"author":427,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[47],"tags":[],"class_list":["post-149438","post","type-post","status-publish","format-standard","hentry","category-neuroscience"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/149438","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/427"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=149438"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/149438\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=149438"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=149438"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=149438"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}