TY - JOUR
T1 - Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations
AU - Iancu, Ovidiu D.
AU - Colville, Alexandre
AU - Oberbeck, Denesa
AU - Darakjian, Priscila
AU - McWeeney, Shannon K.
AU - Hitzemann, Robert
N1 - Publisher Copyright:
© 2015 Iancu, Colville, Oberbeck, Darakjian, McWeeney and Hitzemann.
PY - 2015
Y1 - 2015
N2 - 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 cotranscriptional 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.
AB - 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 cotranscriptional 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.
KW - Alternative splicing
KW - Brain transcriptome
KW - Gene coexpression
KW - Gene cosplicing
KW - Scale-free gene networks
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U2 - 10.3389/fgene.2015.00174
DO - 10.3389/fgene.2015.00174
M3 - Article
AN - SCOPUS:84940100469
SN - 1664-8021
VL - 6
JO - Frontiers in Genetics
JF - Frontiers in Genetics
IS - MAY
M1 - 174
ER -