Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations.
Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations.
复制标题
使用WGCNA和壁炉架相关性的哺乳动物脑RNA-seq数据的固定网络分析。
DOI：
10.3389/fgene.2015.00174
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发表时间：
2015
影响因子：
3.7
通讯作者：
Hitzemann R
中科院分区：
文献类型：
--
作者：
Iancu OD;Colville A;Oberbeck D;Darakjian P;McWeeney SK;Hitzemann R
在物种和组织中，特别是在哺乳动物的大脑中，基因异构体的产生是广泛的。虽然基因表达协调以前被描述为一个无标度的共表达网络，转录组范围内的异构体生产协调的性质研究较少。在这里，我们评估了系统级的性质，在小鼠，猕猴和人脑的基因表达数据，使用一种新的网络推理过程中的共剪接。基因表示为外显子计数的向量/列表，并且对外显子包含率敏感的距离测量量化样品之间的差异。对于所有的基因对，距离矩阵是相关的样品，导致共剪接或共转录网络矩阵。我们表明，网络，包括共剪接信息是无标度的，不同的共表达。在捕获共剪接的网络中，我们发现了一组具有独特特征的新枢纽，将其与共表达枢纽区分开来：神经生物学功能通路中的重代表性，与神经元和神经胶质细胞标记的强烈重叠，长编码长度，以及大量外显子和注释转录本。此外，共剪接枢纽富含与自闭症谱系障碍相关的基因。跨真核生物的共剪接枢纽同源物显示显著增加的内含子长度，但稳定的编码区长度。共享的转录因子结合位点增加共表达，但不增加共剪接;剪接因子结合位点则相反。具有蛋白质-蛋白质相互作用的基因具有很强的共表达和共剪接。影响网络的其他因素包括共享microRNA结合位点，纹状体内的空间共定位，以及共享染色体折叠结构域。共剪接网络模式在物种间保持相对稳定。
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.
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影响因子：
14.9
作者：
Chatr-Aryamontri A;Breitkreutz BJ;Heinicke S;Boucher L;Winter A;Stark C;Nixon J;Ramage L;Kolas N;O'Donnell L;Reguly T;Breitkreutz A;Sellam A;Chen D;Chang C;Rust J;Livstone M;Oughtred R;Dolinski K;Tyers M
通讯作者：
Tyers M
影响因子：
12.3
作者：
Chen L;Zheng S
通讯作者：
Zheng S
影响因子：
3.7
作者：
Allen JD;Xie Y;Chen M;Girard L;Xiao G
通讯作者：
Xiao G
影响因子：
5.8
作者：
Aschoff, Moritz;Hotz-Wagenblatt, Agnes;Koenig, Rainer
通讯作者：
Koenig, Rainer
影响因子：
12.3
作者：
Akerman M;David-Eden H;Pinter RY;Mandel-Gutfreund Y
通讯作者：
Mandel-Gutfreund Y