title: A new method for discovering disease-specific MiRNA-target regulatory networks.
abstract: Genes and their expression regulation are among the key factors in the comprehension of the genesis and development of complex diseases. In this context, microRNAs (miRNAs) are post-transcriptional regulators that play an important role in gene expression since they are frequently deregulated in pathologies like cardiovascular disease and cancer. In vitro validation of miRNA--targets regulation is often too expensive and time consuming to be carried out for every possible alternative. As a result, a tool able to provide some criteria to prioritize trials is becoming a pressing need. Moreover, before planning in vitro experiments, the scientist needs to evaluate the miRNA-target genes interaction network. In this paper we describe the miRable method whose purpose is to identify new potentially relevant genes and their interaction networks associate to a specific pathology. To achieve this goal miRable follows a system biology approach integrating together general-purpose medical knowledge (literature, Protein-Protein Interaction networks, prediction tools) and pathology specific data (gene expression data). A case study on Prostate Cancer has shown that miRable is able to: 1) find new potential miRNA-targets pairs, 2) highlight novel genes potentially involved in a disease but never or little studied before, 3) reconstruct all possible regulatory subnetworks starting from the literature to expand the knowledge on the regulation of miRNA regulatory mechanisms.
authors.affiliation: Institute of Informatics and Telematics (IIT), National Research Council (CNR), Via G. Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Baglioni
authors.affiliation: Laboratory of Integrative Systems Medicine (LISM), Institute of Informatics and Telematics (IIT) and Institute of Clinical Physiology (IFC), National Research Council (CNR), Via G. Moruzzi 1, 56124, Pisa, Italy; Department of Computer Science, University of Pisa, Largo Bruno Pontecorvo 3, 56127, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Russo
authors.affiliation: Institute of Informatics and Telematics (IIT), National Research Council (CNR), Via G. Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Geraci
authors.affiliation: Institute of Clinical Physiology (IFC), National Research Council (CNR), Via G. Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Rizzo
authors.affiliation: Laboratory of Integrative Systems Medicine (LISM), Institute of Informatics and Telematics (IIT) and Institute of Clinical Physiology (IFC), National Research Council (CNR), Via G. Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rainaldi
authors.affiliation: Laboratory of Integrative Systems Medicine (LISM), Institute of Informatics and Telematics (IIT) and Institute of Clinical Physiology (IFC), National Research Council (CNR), Via G. Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pellegrini
mesh_terms: D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
references.citation: Bioinformatics. 2009 Dec 1;25(23):3049-55
references.pmid: 19789267
references.citation: PLoS One. 2012;7(10):e47786
references.pmid: 23094086
references.citation: Brief Bioinform. 2013 May;14(3):263-78
references.pmid: 22692086
references.citation: Cancer Cell. 2010 Jul 13;18(1):11-22
references.pmid: 20579941
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D149-53
references.pmid: 18158296
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: BMC Syst Biol. 2013 Oct 16;7 Suppl 3:S6
references.pmid: 24555436
references.citation: J Biomed Biotechnol. 2012;2012:679563
references.pmid: 23091353
references.citation: J Mol Endocrinol. 2014 Jun;52(3):R257-65
references.pmid: 24740738
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: Am J Transl Res. 2009;1(1):62-71
references.pmid: 19966939
references.citation: PLoS One. 2013;8(1):e55502
references.pmid: 23383207
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D816-23
references.pmid: 23203989
references.citation: BMC Genomics. 2012;13 Suppl 8:S20
references.pmid: 23282288
references.citation: Nucleic Acids Res. 2012 Jul;40(Web Server issue):W13-21
references.pmid: 22618880
references.citation: Nat Genet. 2007 Oct;39(10):1278-84
references.pmid: 17893677
references.citation: FEBS Lett. 2005 Oct 31;579(26):5904-10
references.pmid: 16214134
references.citation: Prostate. 2012 Oct 1;72(14):1514-22
references.pmid: 22314666
references.citation: Oncol Rep. 2014 Mar;31(3):1429-36
references.pmid: 24452363
references.citation: Genome Res. 2011 Jul;21(7):1109-21
references.pmid: 21536720
references.citation: BMC Genomics. 2014;15 Suppl 3:S4
references.pmid: 25077952
references.citation: Tumour Biol. 2014 Aug;35(8):8319-28
references.pmid: 24859835
references.citation: Biochim Biophys Acta. 2014 Mar;1843(3):508-16
references.pmid: 24316134
references.citation: J Immunol. 2012 Jun 1;188(11):5500-10
references.pmid: 22544933
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D78-85
references.pmid: 24304892
references.citation: Genome Res. 2008 Apr;18(4):644-52
references.pmid: 18381899
references.citation: Nat Methods. 2006 Nov;3(11):881-6
references.pmid: 17060911
references.citation: PLoS One. 2007 Feb 14;2(2):e203
references.pmid: 17301878