title: PTHGRN: unraveling post-translational hierarchical gene regulatory networks using PPI, ChIP-seq and gene expression data.
abstract: Interactions among transcriptional factors (TFs), cofactors and other proteins or enzymes can affect transcriptional regulatory capabilities of eukaryotic organisms. Post-translational modifications (PTMs) cooperate with TFs and epigenetic alterations to constitute a hierarchical complexity in transcriptional gene regulation. While clearly implicated in biological processes, our understanding of these complex regulatory mechanisms is still limited and incomplete. Various online software have been proposed for uncovering transcriptional and epigenetic regulatory networks, however, there is a lack of effective web-based software capable of constructing underlying interactive organizations between post-translational and transcriptional regulatory components. Here, we present an open web server, post-translational hierarchical gene regulatory network (PTHGRN) to unravel relationships among PTMs, TFs, epigenetic modifications and gene expression. PTHGRN utilizes a graphical Gaussian model with partial least squares regression-based methodology, and is able to integrate protein-protein interactions, ChIP-seq and gene expression data and to capture essential regulation features behind high-throughput data. The server provides an integrative platform for users to analyze ready-to-use public high-throughput Omics resources or upload their own data for systems biology study. Users can choose various parameters in the method, build network topologies of interests and dissect their associations with biological functions. Application of the software to stem cell and breast cancer demonstrates that it is an effective tool for understanding regulatory mechanisms in biological complex systems. PTHGRN web server is publically available at web site http://www.byanbioinfo.org/pthgrn.
authors.affiliation: Department of Biology, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.
authors.forename: Daogang
authors.initials: D
authors.lastname: Guan
authors.affiliation: Department of Biology, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.
authors.forename: Jiaofang
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Biology, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and HKU-SIRI, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Panwen
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and HKU-SIRI, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Internal Medicine and Biochemistry, Rush University Medical Center, Chicago, Illinois 60612, USA.
authors.forename: Youping
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Stem Cell & Regenerative Medicine Consortium, LKS Faculty of Medicine and Department of Physiology, The University of Hong Kong, Hong Kong SAR, China bohelerk@hku.hk.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Boheler
authors.affiliation: Department of Biochemistry and HKU-SIRI, The University of Hong Kong, Hong Kong SAR, China Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China junwen@uw.edu.
authors.forename: Junwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biology, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China Stem Cell & Regenerative Medicine Consortium, LKS Faculty of Medicine and Department of Physiology, The University of Hong Kong, Hong Kong SAR, China yanbinai6017@gmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020407:Internet; D061986:MCF-7 Cells; D051379:Mice; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D051381:Rats; D012984:Software; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors