title: Identifying multi-layer gene regulatory modules from multi-dimensional genomic data.
abstract: BACKGROUND
  Eukaryotic gene expression (GE) is subjected to precisely coordinated multi-layer controls, across the levels of epigenetic, transcriptional and post-transcriptional regulations. Recently, the emerging multi-dimensional genomic dataset has provided unprecedented opportunities to study the cross-layer regulatory interplay. In these datasets, the same set of samples is profiled on several layers of genomic activities, e.g. copy number variation (CNV), DNA methylation (DM), GE and microRNA expression (ME). However, suitable analysis methods for such data are currently sparse.
  
  
  RESULTS
  In this article, we introduced a sparse Multi-Block Partial Least Squares (sMBPLS) regression method to identify multi-dimensional regulatory modules from this new type of data. A multi-dimensional regulatory module contains sets of regulatory factors from different layers that are likely to jointly contribute to a local 'gene expression factory'. We demonstrated the performance of our method on the simulated data as well as on The Cancer Genomic Atlas Ovarian Cancer datasets including the CNV, DM, ME and GE data measured on 230 samples. We showed that majority of identified modules have significant functional and transcriptional enrichment, higher than that observed in modules identified using only a single type of genomic data. Our network analysis of the modules revealed that the CNV, DM and microRNA can have coupled impact on expression of important oncogenes and tumor suppressor genes.
  
  
  METHODS
  The source code implemented by MATLAB is freely available at: http://zhoulab.usc.edu/sMBPLS/.
  
  
  BACKGROUND
  xjzhou@usc.edu
  
  
  BACKGROUND
  Supplementary material are available at Bioinformatics online.
authors.affiliation: Program in Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Li
authors.forename: Shihua
authors.initials: S
authors.lastname: Zhang
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Liu
authors.forename: Xianghong Jasmine
authors.initials: XJ
authors.lastname: Zhou
mesh_terms: D019295:Computational Biology / Q000379:methods*; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000235:genetics; D012044:Regression Analysis
chemical_list: D035683:MicroRNAs