Journal ArticleDOI
A General Framework for Weighted Gene Co-Expression Network Analysis
Bin Zhang,Steve Horvath +1 more
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A general framework for `soft' thresholding that assigns a connection weight to each gene pair is described and several node connectivity measures are introduced and provided empirical evidence that they can be important for predicting the biological significance of a gene.Abstract:
Gene co-expression networks are increasingly used to explore the system-level functionality of genes. The network construction is conceptually straightforward: nodes represent genes and nodes are connected if the corresponding genes are significantly co-expressed across appropriately chosen tissue samples. In reality, it is tricky to define the connections between the nodes in such networks. An important question is whether it is biologically meaningful to encode gene co-expression using binary information (connected=1, unconnected=0). We describe a general framework for ;soft' thresholding that assigns a connection weight to each gene pair. This leads us to define the notion of a weighted gene co-expression network. For soft thresholding we propose several adjacency functions that convert the co-expression measure to a connection weight. For determining the parameters of the adjacency function, we propose a biologically motivated criterion (referred to as the scale-free topology criterion). We generalize the following important network concepts to the case of weighted networks. First, we introduce several node connectivity measures and provide empirical evidence that they can be important for predicting the biological significance of a gene. Second, we provide theoretical and empirical evidence that the ;weighted' topological overlap measure (used to define gene modules) leads to more cohesive modules than its ;unweighted' counterpart. Third, we generalize the clustering coefficient to weighted networks. Unlike the unweighted clustering coefficient, the weighted clustering coefficient is not inversely related to the connectivity. We provide a model that shows how an inverse relationship between clustering coefficient and connectivity arises from hard thresholding. We apply our methods to simulated data, a cancer microarray data set, and a yeast microarray data set.read more
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Precise temporal regulation of alternative splicing during neural development.
Sebastien M. Weyn-Vanhentenryck,Huijuan Feng,Huijuan Feng,Dmytro Ustianenko,Rachel Duffié,Qinghong Yan,Qinghong Yan,Martin Jacko,Jose C. Martinez,Marianne Goodwin,Xuegong Zhang,Ulrich Hengst,Stavros Lomvardas,Maurice S. Swanson,Chaolin Zhang +14 more
TL;DR: This study identifies two major waves of developmental switches under the control of distinct combinations of RNA-binding proteins in central and peripheral nervous systems.
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Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains
Gabriel E. Hoffman,Brigham J. Hartley,Erin Flaherty,Ian Ladran,Peter Gochman,Douglas M. Ruderfer,Douglas M. Ruderfer,Eli A. Stahl,Judith L. Rapoport,Pamela Sklar,Kristen J. Brennand +10 more
TL;DR: A method is devised to account for gene expression variations in hiPSC-derived neurons from patients with childhood-onset schizophrenia by reducing the stochastic effects of the differentiation process and increasing the concordance with post-mortem data sets.
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Genome-wide significant loci: how important are they? Systems genetics to understand heritability of coronary artery disease and other common complex disorders.
TL;DR: Systems genetics is proposed as a complementary approach to unlocking the CAD heritability and etiology by leveraging systems-based genetic approaches, and can help reveal the full genetic basis of common complex disorders, enabling novel diagnostic and therapeutic opportunities.
Journal ArticleDOI
Transcriptional profiles of bovine in vivo pre-implantation development.
Zongliang Jiang,Jiangwen Sun,Dong Hong,Oscar Junhong Luo,Zheng Xinbao,Craig Obergfell,Yong Tang,Jinbo Bi,Rachel J. O’Neill,Yijun Ruan,Jingbo Chen,Xiuchun Cindy Tian +11 more
TL;DR: This study provides a comprehensive examination of gene activities in bovine embryos and identified little-known potential master regulators of pre-implantation development, demonstrating that bovines are better models for human embryonic development.
Journal ArticleDOI
Sex differences in the human peripheral blood transcriptome
Rick Jansen,Sandra Batista,Andrew Brooks,Jay A. Tischfield,Gonneke Willemsen,Gerard van Grootheest,Jouke-Jan Hottenga,Yuri Milaneschi,Hamdi Mbarek,Vered Madar,Wouter J. Peyrot,Jacqueline M. Vink,Cor L. Verweij,Eco J. C. de Geus,Johannes H. Smit,Fred A. Wright,Patrick F. Sullivan,Dorret I. Boomsma,Brenda W.J.H. Penninx +18 more
TL;DR: This study indicates that sex-bias in gene expression is extensive and may underlie sex-differences in the prevalence of common diseases.
References
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