Meta-analysis of transcriptional regulatory networks for lipid metabolism in neural cells from schizophrenia patients based on an open-source intelligence approach
•Transcriptional networks in the schizophrenia neural cells were reconstructed.•Regulation via enhancers occupied more than half of the edges of the networks.•Meta-analysis revealed commonly used network modules over multiple datasets.•Enrichment of SNPs suggested associations of schizophrenia with...
Gespeichert in:
Veröffentlicht in: | Neuroscience research 2022-02, Vol.175, p.82-97 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 97 |
---|---|
container_issue | |
container_start_page | 82 |
container_title | Neuroscience research |
container_volume | 175 |
creator | Okamoto, Lisa Watanabe, Soyoka Deno, Senka Nie, Xiang Maruyama, Junichi Tomita, Masaru Hatano, Atsushi Yugi, Katsuyuki |
description | •Transcriptional networks in the schizophrenia neural cells were reconstructed.•Regulation via enhancers occupied more than half of the edges of the networks.•Meta-analysis revealed commonly used network modules over multiple datasets.•Enrichment of SNPs suggested associations of schizophrenia with several functions.
There have been a number of reports about the transcriptional regulatory networks in schizophrenia. However, most of these studies were based on a specific transcription factor or a single dataset, an approach that is inadequate to understand the diverse etiology and underlying common characteristics of schizophrenia. Here we reconstructed and compared the transcriptional regulatory network for lipid metabolism enzymes using 15 public transcriptome datasets of neural cells from schizophrenia patients. Since many of the well-known schizophrenia-related SNPs are in enhancers, we reconstructed a network including enhancer-dependent regulation and found that 53.3 % of the total number of edges (7,577 pairs) involved regulation via enhancers. By examining multiple datasets, we found common and unique transcriptional modes of regulation. Furthermore, enrichment analysis of SNPs that were connected with genes in the transcriptional regulatory networks by eQTL suggested an association with hematological cell counts and some other traits/diseases, whose relationship to schizophrenia was either not or insufficiently reported in previous studies. Based on these results, we suggest that in future studies on schizophrenia, information on genotype, comorbidities and hematological cell counts should be included, along with the transcriptome, for a more detailed genetic stratification and mechanistic exploration of schizophrenia. |
doi_str_mv | 10.1016/j.neures.2021.12.006 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2616601437</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0168010221002625</els_id><sourcerecordid>2616601437</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-fe9615787e4d77981b763833b616653e81c2378f95a92f22baef24393a72a11c3</originalsourceid><addsrcrecordid>eNp9kc2O1DAQhC0EYoeFN0DIRy4Z3HYmTi5IaMWftIgLnC3H6ex4SOzgdkDD6_CiOJqFIyfL1ldV3S7GnoPYg4Dm1WkfcE1Ieykk7EHuhWgesB20WlYtADxku4K1lQAhr9gTopMQQnW1esyuVN3pDhq1Y78_YbaVDXY6kyceR56TDeSSX7KP5ZknvFsnm2M684D5Z0zfiI8x8ckvfuBzkfdx8jRzH_g2UZE4nKYCpThzckf_Ky7HhMFbvtjsMWTivSUceAzcBh4XDBXFNTksHrlo_R2GcrHLkqJ1x6fs0Wgnwmf35zX7-u7tl5sP1e3n9x9v3txWrtZ1rkbsGjjoVmM9aN210OtGtUr1DTTNQWELTirdjt3BdnKUsrc4ylp1ymppAZy6Zi8vviX2-4qUzexp28UGjCsZuRkJqJUuaH1BXYpECUezJD_bdDYgzFaPOZlLPWarx4A0pZ4ie3GfsPYzDv9Ef_sowOsLgGXPHx6TIee3zxh8QpfNEP3_E_4AQxOnCQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2616601437</pqid></control><display><type>article</type><title>Meta-analysis of transcriptional regulatory networks for lipid metabolism in neural cells from schizophrenia patients based on an open-source intelligence approach</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Okamoto, Lisa ; Watanabe, Soyoka ; Deno, Senka ; Nie, Xiang ; Maruyama, Junichi ; Tomita, Masaru ; Hatano, Atsushi ; Yugi, Katsuyuki</creator><creatorcontrib>Okamoto, Lisa ; Watanabe, Soyoka ; Deno, Senka ; Nie, Xiang ; Maruyama, Junichi ; Tomita, Masaru ; Hatano, Atsushi ; Yugi, Katsuyuki</creatorcontrib><description>•Transcriptional networks in the schizophrenia neural cells were reconstructed.•Regulation via enhancers occupied more than half of the edges of the networks.•Meta-analysis revealed commonly used network modules over multiple datasets.•Enrichment of SNPs suggested associations of schizophrenia with several functions.
There have been a number of reports about the transcriptional regulatory networks in schizophrenia. However, most of these studies were based on a specific transcription factor or a single dataset, an approach that is inadequate to understand the diverse etiology and underlying common characteristics of schizophrenia. Here we reconstructed and compared the transcriptional regulatory network for lipid metabolism enzymes using 15 public transcriptome datasets of neural cells from schizophrenia patients. Since many of the well-known schizophrenia-related SNPs are in enhancers, we reconstructed a network including enhancer-dependent regulation and found that 53.3 % of the total number of edges (7,577 pairs) involved regulation via enhancers. By examining multiple datasets, we found common and unique transcriptional modes of regulation. Furthermore, enrichment analysis of SNPs that were connected with genes in the transcriptional regulatory networks by eQTL suggested an association with hematological cell counts and some other traits/diseases, whose relationship to schizophrenia was either not or insufficiently reported in previous studies. Based on these results, we suggest that in future studies on schizophrenia, information on genotype, comorbidities and hematological cell counts should be included, along with the transcriptome, for a more detailed genetic stratification and mechanistic exploration of schizophrenia.</description><identifier>ISSN: 0168-0102</identifier><identifier>EISSN: 1872-8111</identifier><identifier>DOI: 10.1016/j.neures.2021.12.006</identifier><identifier>PMID: 34979163</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Enhancer ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Lipid metabolism ; Lipid Metabolism - genetics ; Meta-analysis ; Open-source intelligence ; Schizophrenia ; Schizophrenia - genetics ; Transcriptional regulatory network</subject><ispartof>Neuroscience research, 2022-02, Vol.175, p.82-97</ispartof><rights>2022 The Authors</rights><rights>Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-fe9615787e4d77981b763833b616653e81c2378f95a92f22baef24393a72a11c3</citedby><cites>FETCH-LOGICAL-c474t-fe9615787e4d77981b763833b616653e81c2378f95a92f22baef24393a72a11c3</cites><orcidid>0000-0002-0386-5080 ; 0000-0003-1816-2289 ; 0000-0002-3665-2700 ; 0000-0002-2046-4289</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neures.2021.12.006$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,3551,27925,27926,45996</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34979163$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Okamoto, Lisa</creatorcontrib><creatorcontrib>Watanabe, Soyoka</creatorcontrib><creatorcontrib>Deno, Senka</creatorcontrib><creatorcontrib>Nie, Xiang</creatorcontrib><creatorcontrib>Maruyama, Junichi</creatorcontrib><creatorcontrib>Tomita, Masaru</creatorcontrib><creatorcontrib>Hatano, Atsushi</creatorcontrib><creatorcontrib>Yugi, Katsuyuki</creatorcontrib><title>Meta-analysis of transcriptional regulatory networks for lipid metabolism in neural cells from schizophrenia patients based on an open-source intelligence approach</title><title>Neuroscience research</title><addtitle>Neurosci Res</addtitle><description>•Transcriptional networks in the schizophrenia neural cells were reconstructed.•Regulation via enhancers occupied more than half of the edges of the networks.•Meta-analysis revealed commonly used network modules over multiple datasets.•Enrichment of SNPs suggested associations of schizophrenia with several functions.
There have been a number of reports about the transcriptional regulatory networks in schizophrenia. However, most of these studies were based on a specific transcription factor or a single dataset, an approach that is inadequate to understand the diverse etiology and underlying common characteristics of schizophrenia. Here we reconstructed and compared the transcriptional regulatory network for lipid metabolism enzymes using 15 public transcriptome datasets of neural cells from schizophrenia patients. Since many of the well-known schizophrenia-related SNPs are in enhancers, we reconstructed a network including enhancer-dependent regulation and found that 53.3 % of the total number of edges (7,577 pairs) involved regulation via enhancers. By examining multiple datasets, we found common and unique transcriptional modes of regulation. Furthermore, enrichment analysis of SNPs that were connected with genes in the transcriptional regulatory networks by eQTL suggested an association with hematological cell counts and some other traits/diseases, whose relationship to schizophrenia was either not or insufficiently reported in previous studies. Based on these results, we suggest that in future studies on schizophrenia, information on genotype, comorbidities and hematological cell counts should be included, along with the transcriptome, for a more detailed genetic stratification and mechanistic exploration of schizophrenia.</description><subject>Enhancer</subject><subject>Gene Expression Regulation</subject><subject>Gene Regulatory Networks</subject><subject>Humans</subject><subject>Lipid metabolism</subject><subject>Lipid Metabolism - genetics</subject><subject>Meta-analysis</subject><subject>Open-source intelligence</subject><subject>Schizophrenia</subject><subject>Schizophrenia - genetics</subject><subject>Transcriptional regulatory network</subject><issn>0168-0102</issn><issn>1872-8111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2O1DAQhC0EYoeFN0DIRy4Z3HYmTi5IaMWftIgLnC3H6ex4SOzgdkDD6_CiOJqFIyfL1ldV3S7GnoPYg4Dm1WkfcE1Ieykk7EHuhWgesB20WlYtADxku4K1lQAhr9gTopMQQnW1esyuVN3pDhq1Y78_YbaVDXY6kyceR56TDeSSX7KP5ZknvFsnm2M684D5Z0zfiI8x8ckvfuBzkfdx8jRzH_g2UZE4nKYCpThzckf_Ky7HhMFbvtjsMWTivSUceAzcBh4XDBXFNTksHrlo_R2GcrHLkqJ1x6fs0Wgnwmf35zX7-u7tl5sP1e3n9x9v3txWrtZ1rkbsGjjoVmM9aN210OtGtUr1DTTNQWELTirdjt3BdnKUsrc4ylp1ymppAZy6Zi8vviX2-4qUzexp28UGjCsZuRkJqJUuaH1BXYpECUezJD_bdDYgzFaPOZlLPWarx4A0pZ4ie3GfsPYzDv9Ef_sowOsLgGXPHx6TIee3zxh8QpfNEP3_E_4AQxOnCQ</recordid><startdate>202202</startdate><enddate>202202</enddate><creator>Okamoto, Lisa</creator><creator>Watanabe, Soyoka</creator><creator>Deno, Senka</creator><creator>Nie, Xiang</creator><creator>Maruyama, Junichi</creator><creator>Tomita, Masaru</creator><creator>Hatano, Atsushi</creator><creator>Yugi, Katsuyuki</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0386-5080</orcidid><orcidid>https://orcid.org/0000-0003-1816-2289</orcidid><orcidid>https://orcid.org/0000-0002-3665-2700</orcidid><orcidid>https://orcid.org/0000-0002-2046-4289</orcidid></search><sort><creationdate>202202</creationdate><title>Meta-analysis of transcriptional regulatory networks for lipid metabolism in neural cells from schizophrenia patients based on an open-source intelligence approach</title><author>Okamoto, Lisa ; Watanabe, Soyoka ; Deno, Senka ; Nie, Xiang ; Maruyama, Junichi ; Tomita, Masaru ; Hatano, Atsushi ; Yugi, Katsuyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-fe9615787e4d77981b763833b616653e81c2378f95a92f22baef24393a72a11c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Enhancer</topic><topic>Gene Expression Regulation</topic><topic>Gene Regulatory Networks</topic><topic>Humans</topic><topic>Lipid metabolism</topic><topic>Lipid Metabolism - genetics</topic><topic>Meta-analysis</topic><topic>Open-source intelligence</topic><topic>Schizophrenia</topic><topic>Schizophrenia - genetics</topic><topic>Transcriptional regulatory network</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Okamoto, Lisa</creatorcontrib><creatorcontrib>Watanabe, Soyoka</creatorcontrib><creatorcontrib>Deno, Senka</creatorcontrib><creatorcontrib>Nie, Xiang</creatorcontrib><creatorcontrib>Maruyama, Junichi</creatorcontrib><creatorcontrib>Tomita, Masaru</creatorcontrib><creatorcontrib>Hatano, Atsushi</creatorcontrib><creatorcontrib>Yugi, Katsuyuki</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Okamoto, Lisa</au><au>Watanabe, Soyoka</au><au>Deno, Senka</au><au>Nie, Xiang</au><au>Maruyama, Junichi</au><au>Tomita, Masaru</au><au>Hatano, Atsushi</au><au>Yugi, Katsuyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Meta-analysis of transcriptional regulatory networks for lipid metabolism in neural cells from schizophrenia patients based on an open-source intelligence approach</atitle><jtitle>Neuroscience research</jtitle><addtitle>Neurosci Res</addtitle><date>2022-02</date><risdate>2022</risdate><volume>175</volume><spage>82</spage><epage>97</epage><pages>82-97</pages><issn>0168-0102</issn><eissn>1872-8111</eissn><abstract>•Transcriptional networks in the schizophrenia neural cells were reconstructed.•Regulation via enhancers occupied more than half of the edges of the networks.•Meta-analysis revealed commonly used network modules over multiple datasets.•Enrichment of SNPs suggested associations of schizophrenia with several functions.
There have been a number of reports about the transcriptional regulatory networks in schizophrenia. However, most of these studies were based on a specific transcription factor or a single dataset, an approach that is inadequate to understand the diverse etiology and underlying common characteristics of schizophrenia. Here we reconstructed and compared the transcriptional regulatory network for lipid metabolism enzymes using 15 public transcriptome datasets of neural cells from schizophrenia patients. Since many of the well-known schizophrenia-related SNPs are in enhancers, we reconstructed a network including enhancer-dependent regulation and found that 53.3 % of the total number of edges (7,577 pairs) involved regulation via enhancers. By examining multiple datasets, we found common and unique transcriptional modes of regulation. Furthermore, enrichment analysis of SNPs that were connected with genes in the transcriptional regulatory networks by eQTL suggested an association with hematological cell counts and some other traits/diseases, whose relationship to schizophrenia was either not or insufficiently reported in previous studies. Based on these results, we suggest that in future studies on schizophrenia, information on genotype, comorbidities and hematological cell counts should be included, along with the transcriptome, for a more detailed genetic stratification and mechanistic exploration of schizophrenia.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>34979163</pmid><doi>10.1016/j.neures.2021.12.006</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-0386-5080</orcidid><orcidid>https://orcid.org/0000-0003-1816-2289</orcidid><orcidid>https://orcid.org/0000-0002-3665-2700</orcidid><orcidid>https://orcid.org/0000-0002-2046-4289</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0168-0102 |
ispartof | Neuroscience research, 2022-02, Vol.175, p.82-97 |
issn | 0168-0102 1872-8111 |
language | eng |
recordid | cdi_proquest_miscellaneous_2616601437 |
source | MEDLINE; Access via ScienceDirect (Elsevier) |
subjects | Enhancer Gene Expression Regulation Gene Regulatory Networks Humans Lipid metabolism Lipid Metabolism - genetics Meta-analysis Open-source intelligence Schizophrenia Schizophrenia - genetics Transcriptional regulatory network |
title | Meta-analysis of transcriptional regulatory networks for lipid metabolism in neural cells from schizophrenia patients based on an open-source intelligence approach |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T14%3A15%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Meta-analysis%20of%20transcriptional%20regulatory%20networks%20for%20lipid%20metabolism%20in%20neural%20cells%20from%20schizophrenia%20patients%20based%20on%20an%20open-source%20intelligence%20approach&rft.jtitle=Neuroscience%20research&rft.au=Okamoto,%20Lisa&rft.date=2022-02&rft.volume=175&rft.spage=82&rft.epage=97&rft.pages=82-97&rft.issn=0168-0102&rft.eissn=1872-8111&rft_id=info:doi/10.1016/j.neures.2021.12.006&rft_dat=%3Cproquest_cross%3E2616601437%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2616601437&rft_id=info:pmid/34979163&rft_els_id=S0168010221002625&rfr_iscdi=true |