title: Altered Pathway Analyzer: A gene expression dataset analysis tool for identification and prioritization of differentially regulated and network rewired pathways.
abstract: Gene connection rewiring is an essential feature of gene network dynamics. Apart from its normal functional role, it may also lead to dysregulated functional states by disturbing pathway homeostasis. Very few computational tools measure rewiring within gene co-expression and its corresponding regulatory networks in order to identify and prioritize altered pathways which may or may not be differentially regulated. We have developed Altered Pathway Analyzer (APA), a microarray dataset analysis tool for identification and prioritization of altered pathways, including those which are differentially regulated by TFs, by quantifying rewired sub-network topology. Moreover, APA also helps in re-prioritization of APA shortlisted altered pathways enriched with context-specific genes. We performed APA analysis of simulated datasets and p53 status NCI-60 cell line microarray data to demonstrate potential of APA for identification of several case-specific altered pathways. APA analysis reveals several altered pathways not detected by other tools evaluated by us. APA analysis of unrelated prostate cancer datasets identifies sample-specific as well as conserved altered biological processes, mainly associated with lipid metabolism, cellular differentiation and proliferation. APA is designed as a cross platform tool which may be transparently customized to perform pathway analysis in different gene expression datasets. APA is freely available at http://bioinfo.icgeb.res.in/APA.
authors.affiliation: Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Kaushik
authors.affiliation: Department of Biochemistry, Jamia Hamdard, Deemed University, New Delhi 110062, India.
authors.forename: Shakir
authors.initials: S
authors.lastname: Ali
authors.affiliation: Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Gupta
mesh_terms: D000465:Algorithms; D045744:Cell Line, Tumor; D003198:Computer Simulation; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D009154:Mutation / Q000235:genetics; D015203:Reproducibility of Results; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53