MultiDCoX: Multi-factor analysis of differential co-expression

Background Differential co-expression signifies change in degree of co-expression of a set of genes among different biological conditions. It has been used to identify differential co-expression networks or interactomes. Many algorithms have been developed for single-factor differential co-expression analysis and applied in a variety of studies. However, in many studies, the samples are characterized by multiple factors such as genetic markers, clinical variables and treatments. No algorithm or methodology is available for multi-factor analysis of differential co-expression. Results We developed a novel formulation and a computationally efficient greedy search algorithm called MultiDCoX to perform multi-factor differential co-expression analysis of transcriptomic data. Simulated data analysis demonstrates that the algorithm can effectively elicit differentially co-expressed (DCX) gene sets and quantify the influence of each factor on co-expression. MultiDCoX analysis of a breast cancer dataset identified interesting biologically meaningful differentially coexpressed (DCX) gene sets along with genetic and clinical factors that influenced the respective differential co-expression. Conclusions MultiDCoX is a space and time efficient procedure to identify differentially co-expressed gene sets and successfully identify influence of individual factors on differential co-expression. Software R function will be available upon request.

[1]  Z. Weng,et al.  A Global Map of p53 Transcription-Factor Binding Sites in the Human Genome , 2006, Cell.

[2]  Paul Pavlidis,et al.  A methodology for the analysis of differential coexpression across the human lifespan , 2009, BMC Bioinformatics.

[3]  Karuturi R. Krishna Murthy,et al.  Significance Analysis and Improved Discovery of Differentially Co-expressed Gene Sets in Microarray Data , 2006, Sixth IEEE International Conference on Data Mining - Workshops (ICDMW'06).

[4]  Karuturi R. Krishna Murthy,et al.  Significance analysis and improved discovery of disease-specific Differentially Co-expressed Gene Sets in microarray data , 2010, Int. J. Data Min. Bioinform..

[5]  Frank Emmert-Streib,et al.  Gene Sets Net Correlations Analysis (GSNCA): a multivariate differential coexpression test for gene sets , 2013, Bioinform..

[6]  F. Stossi,et al.  Whole-Genome Cartography of Estrogen Receptor α Binding Sites , 2007, PLoS genetics.

[7]  M. West,et al.  An integrative approach to characterize disease-specific pathways and their coordination: a case study in cancer , 2008, BMC Genomics.

[8]  S. Horvath,et al.  Weighted gene coexpression network analysis strategies applied to mouse weight , 2007, Mammalian Genome.

[9]  Lucinda K. Southworth,et al.  Aging Mice Show a Decreasing Correlation of Gene Expression within Genetic Modules , 2009, PLoS genetics.

[10]  Carlos Prieto,et al.  Algorithm to find gene expression profiles of deregulation and identify families of disease-altered genes , 2006, Bioinform..

[11]  Karuturi R. Krishna Murthy,et al.  Differential Friendly Neighbors Algorithm for Differential Relationships Based Gene Selection and Classification using Microarray Data , 2006, DMIN.

[12]  Rainer Spang,et al.  Finding disease specific alterations in the co-expression of genes , 2004, ISMB/ECCB.

[13]  Donald Geman,et al.  Large-scale integration of cancer microarray data identifies a robust common cancer signature , 2007, BMC Bioinformatics.

[14]  Sangsoo Kim,et al.  Gene expression Differential coexpression analysis using microarray data and its application to human cancer , 2005 .

[15]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[16]  John J Dunn,et al.  Distinct p53 genomic binding patterns in normal and cancer-derived human cells , 2011, Cell cycle.

[17]  Rainer Breitling,et al.  DiffCoEx: a simple and sensitive method to find differentially coexpressed gene modules , 2010, BMC Bioinformatics.

[18]  Clifford A. Meyer,et al.  FoxA1 Translates Epigenetic Signatures into Enhancer-Driven Lineage-Specific Transcription , 2008, Cell.

[19]  Ju Han Kim,et al.  Identifying set-wise differential co-expression in gene expression microarray data , 2009, BMC Bioinformatics.

[20]  Q. Lin,et al.  Evidence of EGR1 as a differentially expressed gene among proliferative skin diseases , 2007, Genomic Medicine.

[21]  T. Vahlberg,et al.  MMP-1 expression has an independent prognostic value in breast cancer , 2011, BMC Cancer.

[22]  Michael Watson,et al.  CoXpress: differential co-expression in gene expression data , 2006, BMC Bioinformatics.

[23]  P. Hall,et al.  An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[24]  E. J. Gregory,et al.  Correlation of primary breast cancer histopathology and estrogen receptor content , 1981, Breast Cancer Research and Treatment.

[25]  Terrence S. Furey,et al.  The UCSC Table Browser data retrieval tool , 2004, Nucleic Acids Res..

[26]  Eric E Schadt,et al.  Elucidating the role of gonadal hormones in sexually dimorphic gene coexpression networks. , 2009, Endocrinology.

[27]  M. Rasti,et al.  p53 Binds to Estrogen Receptor 1 Promoter in Human Breast Cancer Cells , 2012, Pathology & Oncology Research.

[28]  Weixiong Zhang,et al.  Analysis of Alzheimer's disease severity across brain regions by topological analysis of gene co-expression networks , 2010, BMC Systems Biology.

[29]  Hsuan-Cheng Huang,et al.  Functional Analysis and Characterization of Differential Coexpression Networks , 2015, Scientific Reports.

[30]  Ross Lazarus,et al.  Quantifying differential gene connectivity between disease states for objective identification of disease-relevant genes , 2011, BMC Systems Biology.

[31]  Christina Kendziorski,et al.  Statistical methods for gene set co-expression analysis , 2009, Bioinform..

[32]  A. G. de la Fuente From 'differential expression' to 'differential networking' - identification of dysfunctional regulatory networks in diseases. , 2010, Trends in genetics : TIG.

[33]  Jeremy J. W. Chen,et al.  Topology-based cancer classification and related pathway mining using microarray data , 2006, Nucleic acids research.

[34]  V. Theodorou,et al.  GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility , 2013, Genome research.

[35]  S. Bergmann,et al.  Comparative Gene Expression Analysis by a Differential Clustering Approach: Application to the Candida albicans Transcription Program , 2005, PLoS genetics.

[36]  A. Rajasekaran,et al.  Estrogen Receptor-α Binds p53 Tumor Suppressor Protein Directly and Represses Its Function* , 2006, Journal of Biological Chemistry.

[37]  S. Horvath,et al.  Conservation and evolution of gene coexpression networks in human and chimpanzee brains , 2006, Proceedings of the National Academy of Sciences.

[38]  Graziano Pesole,et al.  p53FamTaG: a database resource of human p53, p63 and p73 direct target genes combining in silico prediction and microarray data , 2007, BMC Bioinformatics.

[39]  Ker-Chau Li,et al.  Genome-wide expression links the electron transfer pathway of Shewanella oneidensis to chemotaxis , 2010, BMC Genomics.

[40]  Karuturi R. Krishna Murthy,et al.  Differential co-expression framework to quantify goodness of biclusters and compare biclustering algorithms , 2010, Algorithms for Molecular Biology.

[41]  G. Gibson,et al.  Epidermal growth factor receptors in non-small cell lung cancer. , 1987, British Journal of Cancer.

[42]  Clifford A. Meyer,et al.  Genome-wide analysis of estrogen receptor binding sites , 2006, Nature Genetics.