Journal ArticleDOI
A General Framework for Weighted Gene Co-Expression Network Analysis
Bin Zhang,Steve Horvath +1 more
TLDR
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
Citations
More filters
Journal ArticleDOI
Integrated Weighted Gene Co-expression Network Analysis with an Application to Chronic Fatigue Syndrome
Angela P. Presson,Eric M. Sobel,Jeanette C. Papp,Charlyn J Suarez,Toni Whistler,Mangalathu S. Rajeevan,Suzanne D. Vernon,Steve Horvath +7 more
TL;DR: It is shown how WGCNA can be combined with genetic marker data to identify disease-related pathways and the causal drivers within them and can easily be used to generate testable genetic hypotheses in other complex disease studies.
Journal ArticleDOI
Secreted Frizzled-Related Protein 4 Reduces Insulin Secretion and Is Overexpressed in Type 2 Diabetes
Taman Mahdi,Sonja Hänzelmann,Sonja Hänzelmann,Albert Salehi,Sarheed Jabar Muhammed,Thomas Reinbothe,Yunzhao Tang,Yunzhao Tang,Annika S. Axelsson,Yuedan Zhou,Xingjun Jing,Peter Almgren,Ulrika Krus,Jalal Taneera,Anna M. Blom,Valeriya Lyssenko,Jonathan L.S. Esguerra,Ola Hansson,Lena Eliasson,Jonathan M. J. Derry,Enming Zhang,Claes B. Wollheim,Leif Groop,Erik Renström,Anders Rosengren,Anders Rosengren +25 more
TL;DR: Elevated systemic SFRP4 caused reduced glucose tolerance through decreased islet expression of Ca(2+) channels and suppressed insulin exocytosis, and provides a link between islet inflammation and impaired insulin secretion.
Journal ArticleDOI
Alzheimer's disease is associated with altered expression of genes involved in immune response and mitochondrial processes in astrocytes
Shobana Sekar,Jacquelyn McDonald,Lori Cuyugan,Jessica Aldrich,Ahmet Kurdoglu,Jonathan Adkins,Geidy E. Serrano,Thomas G. Beach,David Craig,Jonathan Valla,Eric M. Reiman,Winnie S. Liang +11 more
TL;DR: The transcriptome of AD PC astrocytes is characterized and differentially expressed mitochondria-related genes including TRMT61B, FASTKD2, and NDUFA4L2 are identified and a number of these genes have been implicated in beta amyloid generation or clearance.
Journal ArticleDOI
Microbial community transcriptional networks are conserved in three domains at ocean basin scales
Frank O. Aylward,John M. Eppley,Jason M. Smith,Francisco P. Chavez,Christopher A. Scholin,Edward F. DeLong,Edward F. DeLong +6 more
TL;DR: It is reported that common temporal and ecological dynamics underpin disparate marine microbial communities, providing the first evidence that trans-Pacific diurnal transcriptional patterns in these communities may regulate ecological and biogeochemical processes across the ocean.
Journal ArticleDOI
Explaining human uniqueness: genome interactions with environment, behaviour and culture.
TL;DR: A genomic and genetic perspective towards molecular variation, systems analysis of gene expression and an organ-systems approach are explored, and it is speculated that aspects of human uniqueness arose because of a primate evolutionary trend towards increasing and irreversible dependence on learned behaviours and culture.
References
More filters
Journal ArticleDOI
Emergence of Scaling in Random Networks
TL;DR: A model based on these two ingredients reproduces the observed stationary scale-free distributions, which indicates that the development of large networks is governed by robust self-organizing phenomena that go beyond the particulars of the individual systems.
Journal ArticleDOI
Statistical mechanics of complex networks
TL;DR: In this paper, a simple model based on the power-law degree distribution of real networks was proposed, which was able to reproduce the power law degree distribution in real networks and to capture the evolution of networks, not just their static topology.
Journal ArticleDOI
Cluster analysis and display of genome-wide expression patterns
TL;DR: A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is described that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression, finding in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function.
Book
Finding Groups in Data: An Introduction to Cluster Analysis
TL;DR: An electrical signal transmission system, applicable to the transmission of signals from trackside hot box detector equipment for railroad locomotives and rolling stock, wherein a basic pulse train is transmitted whereof the pulses are of a selected first amplitude and represent a train axle count.
Journal ArticleDOI
R: A Language for Data Analysis and Graphics
Ross Ihaka,Robert Gentleman +1 more
TL;DR: In this article, the authors discuss their experience designing and implementing a statistical computing language, which combines what they felt were useful features from two existing computer languages, and they feel that the new language provides advantages in the areas of portability, computational efficiency, memory management, and scope.
Related Papers (5)
WGCNA: an R package for weighted correlation network analysis.
Peter Langfelder,Steve Horvath +1 more
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
Gene Ontology: tool for the unification of biology
M Ashburner,Catherine A. Ball,Judith A. Blake,David Botstein,Heather Butler,J. M. Cherry,Allan Peter Davis,Kara Dolinski,Selina S. Dwight,J.T. Eppig,Midori A. Harris,David P. Hill,Laurie Issel-Tarver,Andrew Kasarskis,Suzanna E. Lewis,John C. Matese,Joel E. Richardson,M. Ringwald,Gerald M. Rubin,Gavin Sherlock +19 more