Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations
Across species and tissues and especially in the mammalian brain, production of gene isoforms is widespread. While gene expression coordination has been previously described as a scale-free coexpression network, the properties of transcriptome-wide isoform production coordination have been less stud...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2015.00174/full |
| _version_ | 1811316047337226240 |
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| author | Ovidiu Dan Iancu Alexandre eColville Denesa eOberbeck Priscila eDarakjian Shannon K McWeeney Robert eHitzemann Robert eHitzemann |
| author_facet | Ovidiu Dan Iancu Alexandre eColville Denesa eOberbeck Priscila eDarakjian Shannon K McWeeney Robert eHitzemann Robert eHitzemann |
| author_sort | Ovidiu Dan Iancu |
| collection | DOAJ |
| description | Across species and tissues and especially in the mammalian brain, production of gene isoforms is widespread. While gene expression coordination has been previously described as a scale-free coexpression network, the properties of transcriptome-wide isoform production coordination have been less studied. Here we evaluate the system-level properties of cosplicing in mouse, macaque and human brain gene expression data using a novel network inference procedure. Genes are represented as vectors/lists of exon counts and distance measures sensitive to exon inclusion rates quantifies differences across samples. For all gene pairs, distance matrices are correlated across samples, resulting in cosplicing or co-transcriptional network matrices. We show that networks including cosplicing information are scale-free and distinct from coexpression. In the networks capturing cosplicing we find a set of novel hubs with unique characteristics distinguishing them from coexpression hubs: heavy representation in neurobiological functional pathways, strong overlap with markers of neurons and neuroglia, long coding lengths, and high number of both exons and annotated transcripts. Further, the cosplicing hubs are enriched in genes associated with autism spectrum disorders. Cosplicing hub homologs across eukaryotes show dramatically increasing intronic lengths but stable coding region lengths. Shared transcription factor binding sites increase coexpression but not cosplicing; the reverse is true for splicing-factor binding sites. Genes with protein-protein interactions have strong coexpression and cosplicing. Additional factors affecting the networks include shared microRNA binding sites, spatial colocalization within the striatum, and sharing a chromosomal folding domain. Cosplicing network patterns remain relatively stable across species. |
| first_indexed | 2024-04-13T11:42:01Z |
| format | Article |
| id | doaj.art-94d7752a23714ba48d58faff3a8a61f2 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T11:42:01Z |
| publishDate | 2015-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-94d7752a23714ba48d58faff3a8a61f22022-12-22T02:48:17ZengFrontiers Media S.A.Frontiers in Genetics1664-80212015-05-01610.3389/fgene.2015.00174127587Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlationsOvidiu Dan Iancu0Alexandre eColville1Denesa eOberbeck2Priscila eDarakjian3Shannon K McWeeney4Robert eHitzemann5Robert eHitzemann6Oregon Health & Science UniversityOregon Health & Science UniversityOregon Health & Science UniversityOregon Health & Science UniversityOregon Health & Science UniversityOregon Health & Science UniversityVeterans Affairs Medical CenterAcross species and tissues and especially in the mammalian brain, production of gene isoforms is widespread. While gene expression coordination has been previously described as a scale-free coexpression network, the properties of transcriptome-wide isoform production coordination have been less studied. Here we evaluate the system-level properties of cosplicing in mouse, macaque and human brain gene expression data using a novel network inference procedure. Genes are represented as vectors/lists of exon counts and distance measures sensitive to exon inclusion rates quantifies differences across samples. For all gene pairs, distance matrices are correlated across samples, resulting in cosplicing or co-transcriptional network matrices. We show that networks including cosplicing information are scale-free and distinct from coexpression. In the networks capturing cosplicing we find a set of novel hubs with unique characteristics distinguishing them from coexpression hubs: heavy representation in neurobiological functional pathways, strong overlap with markers of neurons and neuroglia, long coding lengths, and high number of both exons and annotated transcripts. Further, the cosplicing hubs are enriched in genes associated with autism spectrum disorders. Cosplicing hub homologs across eukaryotes show dramatically increasing intronic lengths but stable coding region lengths. Shared transcription factor binding sites increase coexpression but not cosplicing; the reverse is true for splicing-factor binding sites. Genes with protein-protein interactions have strong coexpression and cosplicing. Additional factors affecting the networks include shared microRNA binding sites, spatial colocalization within the striatum, and sharing a chromosomal folding domain. Cosplicing network patterns remain relatively stable across species.http://journal.frontiersin.org/Journal/10.3389/fgene.2015.00174/fullAlternative Splicingscale free networksGene coexpressiongene cosplicingbrain transcriptome |
| spellingShingle | Ovidiu Dan Iancu Alexandre eColville Denesa eOberbeck Priscila eDarakjian Shannon K McWeeney Robert eHitzemann Robert eHitzemann Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations Frontiers in Genetics Alternative Splicing scale free networks Gene coexpression gene cosplicing brain transcriptome |
| title | Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations |
| title_full | Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations |
| title_fullStr | Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations |
| title_full_unstemmed | Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations |
| title_short | Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations |
| title_sort | cosplicing network analysis of mammalian brain rna seq data utilizing wgcna and mantel correlations |
| topic | Alternative Splicing scale free networks Gene coexpression gene cosplicing brain transcriptome |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2015.00174/full |
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