Co-expression networks reveal the tissue-specific regulation of transcription and splicing
Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression...
| Authors: | ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2017 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/69052 |
| Online Access: | http://hdl.handle.net/10230/69052 http://dx.doi.org/10.1101/gr.216721.116 |
| Access Level: | Open access |
| Keyword: | Traducció genètica Codi genètic Transcripció genètica |
| _version_ | 1878740999372537856 |
|---|---|
| author | Saha, Ashis |
| author2 | Kim, Yungil Gewirtz, Ariel D.H. Jo, Brian Gao, Chuan McDowell, Ian C. GTEx Consortium Reverter Comes, Ferran Engelhardt, Barbara E. Battle, Alexis |
| author2_role | author author author author author author author author author |
| author_browse | Battle, Alexis Engelhardt, Barbara E. GTEx Consortium Gao, Chuan Gewirtz, Ariel D.H. Jo, Brian Kim, Yungil McDowell, Ian C. Reverter Comes, Ferran Saha, Ashis |
| author_facet | Saha, Ashis Kim, Yungil Gewirtz, Ariel D.H. Jo, Brian Gao, Chuan McDowell, Ian C. GTEx Consortium Reverter Comes, Ferran Engelhardt, Barbara E. Battle, Alexis |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| description | Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_dd3e5cb2cbb2497cfb7e8f0ec01d566e |
| institution | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:10230/69052 |
| publishDate | 2017 |
| publishDateSort | 2017 |
| publisher | Cold Spring Harbor Laboratory Press (CSHL Press) |
| publisherStr | Cold Spring Harbor Laboratory Press (CSHL Press) |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Co-expression networks reveal the tissue-specific regulation of transcription and splicing Saha, Ashis Kim, Yungil Gewirtz, Ariel D.H. Jo, Brian Gao, Chuan McDowell, Ian C. GTEx Consortium Reverter Comes, Ferran Engelhardt, Barbara E. Battle, Alexis Traducció genètica Codi genètic Transcripció genètica Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. Cold Spring Harbor Laboratory Press (CSHL Press) http://hdl.handle.net/10230/69052 http://dx.doi.org/10.1101/gr.216721.116 |
| spellingShingle | Co-expression networks reveal the tissue-specific regulation of transcription and splicing Saha, Ashis Traducció genètica Codi genètic Transcripció genètica |
| status_str | publishedVersion |
| title | Co-expression networks reveal the tissue-specific regulation of transcription and splicing |
| title_full | Co-expression networks reveal the tissue-specific regulation of transcription and splicing |
| title_fullStr | Co-expression networks reveal the tissue-specific regulation of transcription and splicing |
| title_full_unstemmed | Co-expression networks reveal the tissue-specific regulation of transcription and splicing |
| title_short | Co-expression networks reveal the tissue-specific regulation of transcription and splicing |
| title_sort | Co-expression networks reveal the tissue-specific regulation of transcription and splicing |
| topic | Traducció genètica Codi genètic Transcripció genètica |
| topic_facet | Traducció genètica Codi genètic Transcripció genètica |
| url | http://hdl.handle.net/10230/69052 http://dx.doi.org/10.1101/gr.216721.116 |