Pivotal role of the muscle-contraction pathway in cryptorchidism and evidence for genomic connections with cardiomyopathy pathways in RASopathies

Handle URI:
http://hdl.handle.net/10754/325271
Title:
Pivotal role of the muscle-contraction pathway in cryptorchidism and evidence for genomic connections with cardiomyopathy pathways in RASopathies
Authors:
Cannistraci, Carlo; Ogorevc, Jernej; Zorc, Minja; Ravasi, Timothy ( 0000-0002-9950-465X ) ; Dovc, Peter; Kunej, Tanja
Abstract:
Background: Cryptorchidism is the most frequent congenital disorder in male children; however the genetic causes of cryptorchidism remain poorly investigated. Comparative integratomics combined with systems biology approach was employed to elucidate genetic factors and molecular pathways underlying testis descent. Methods. Literature mining was performed to collect genomic loci associated with cryptorchidism in seven mammalian species. Information regarding the collected candidate genes was stored in MySQL relational database. Genomic view of the loci was presented using Flash GViewer web tool (http://gmod.org/wiki/Flashgviewer/). DAVID Bioinformatics Resources 6.7 was used for pathway enrichment analysis. Cytoscape plug-in PiNGO 1.11 was employed for protein-network-based prediction of novel candidate genes. Relevant protein-protein interactions were confirmed and visualized using the STRING database (version 9.0). Results. The developed cryptorchidism gene atlas includes 217 candidate loci (genes, regions involved in chromosomal mutations, and copy number variations) identified at the genomic, transcriptomic, and proteomic level. Human orthologs of the collected candidate loci were presented using a genomic map viewer. The cryptorchidism gene atlas is freely available online: http://www.integratomics-time.com/cryptorchidism/. Pathway analysis suggested the presence of twelve enriched pathways associated with the list of 179 literature-derived candidate genes. Additionally, a list of 43 network-predicted novel candidate genes was significantly associated with four enriched pathways. Joint pathway analysis of the collected and predicted candidate genes revealed the pivotal importance of the muscle-contraction pathway in cryptorchidism and evidence for genomic associations with cardiomyopathy pathways in RASopathies. Conclusions: The developed gene atlas represents an important resource for the scientific community researching genetics of cryptorchidism. The collected data will further facilitate development of novel genetic markers and could be of interest for functional studies in animals and human. The proposed network-based systems biology approach elucidates molecular mechanisms underlying co-presence of cryptorchidism and cardiomyopathy in RASopathies. Such approach could also aid in molecular explanation of co-presence of diverse and apparently unrelated clinical manifestations in other syndromes. 2013 Cannistraci et al.; licensee BioMed Central Ltd.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computational Bioscience Research Center (CBRC)
Citation:
Cannistraci CV, Ogorevc J, Zorc M, Ravasi T, Dovc P, et al. (2013) Pivotal role of the muscle-contraction pathway in cryptorchidism and evidence for genomic connections with cardiomyopathy pathways in RASopathies. BMC Med Genomics 6: 5. doi:10.1186/1755-8794-6-5.
Publisher:
Springer Nature
Journal:
BMC Medical Genomics
Issue Date:
14-Feb-2013
DOI:
10.1186/1755-8794-6-5
PubMed ID:
23410028
PubMed Central ID:
PMC3626861
Type:
Article
ISSN:
17558794
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorCannistraci, Carloen
dc.contributor.authorOgorevc, Jernejen
dc.contributor.authorZorc, Minjaen
dc.contributor.authorRavasi, Timothyen
dc.contributor.authorDovc, Peteren
dc.contributor.authorKunej, Tanjaen
dc.date.accessioned2014-08-27T09:43:58Z-
dc.date.available2014-08-27T09:43:58Z-
dc.date.issued2013-02-14en
dc.identifier.citationCannistraci CV, Ogorevc J, Zorc M, Ravasi T, Dovc P, et al. (2013) Pivotal role of the muscle-contraction pathway in cryptorchidism and evidence for genomic connections with cardiomyopathy pathways in RASopathies. BMC Med Genomics 6: 5. doi:10.1186/1755-8794-6-5.en
dc.identifier.issn17558794en
dc.identifier.pmid23410028en
dc.identifier.doi10.1186/1755-8794-6-5en
dc.identifier.urihttp://hdl.handle.net/10754/325271en
dc.description.abstractBackground: Cryptorchidism is the most frequent congenital disorder in male children; however the genetic causes of cryptorchidism remain poorly investigated. Comparative integratomics combined with systems biology approach was employed to elucidate genetic factors and molecular pathways underlying testis descent. Methods. Literature mining was performed to collect genomic loci associated with cryptorchidism in seven mammalian species. Information regarding the collected candidate genes was stored in MySQL relational database. Genomic view of the loci was presented using Flash GViewer web tool (http://gmod.org/wiki/Flashgviewer/). DAVID Bioinformatics Resources 6.7 was used for pathway enrichment analysis. Cytoscape plug-in PiNGO 1.11 was employed for protein-network-based prediction of novel candidate genes. Relevant protein-protein interactions were confirmed and visualized using the STRING database (version 9.0). Results. The developed cryptorchidism gene atlas includes 217 candidate loci (genes, regions involved in chromosomal mutations, and copy number variations) identified at the genomic, transcriptomic, and proteomic level. Human orthologs of the collected candidate loci were presented using a genomic map viewer. The cryptorchidism gene atlas is freely available online: http://www.integratomics-time.com/cryptorchidism/. Pathway analysis suggested the presence of twelve enriched pathways associated with the list of 179 literature-derived candidate genes. Additionally, a list of 43 network-predicted novel candidate genes was significantly associated with four enriched pathways. Joint pathway analysis of the collected and predicted candidate genes revealed the pivotal importance of the muscle-contraction pathway in cryptorchidism and evidence for genomic associations with cardiomyopathy pathways in RASopathies. Conclusions: The developed gene atlas represents an important resource for the scientific community researching genetics of cryptorchidism. The collected data will further facilitate development of novel genetic markers and could be of interest for functional studies in animals and human. The proposed network-based systems biology approach elucidates molecular mechanisms underlying co-presence of cryptorchidism and cardiomyopathy in RASopathies. Such approach could also aid in molecular explanation of co-presence of diverse and apparently unrelated clinical manifestations in other syndromes. 2013 Cannistraci et al.; licensee BioMed Central Ltd.en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en
dc.subjectCardiomyopathyen
dc.subjectComparative integratomicsen
dc.subjectCryptorchidismen
dc.subjectMuscle-contraction pathwayen
dc.subjectProtein-protein interactionsen
dc.subjectRASopathyen
dc.subjectSystems biologyen
dc.subjectUndescended testesen
dc.subjectbeta calcitonin gene related peptideen
dc.subjectcalcitonin gene related peptideen
dc.subjectbioinformaticsen
dc.subjectbiomicsen
dc.subjectcardiomyopathyen
dc.subjectchromosome aberrationen
dc.subjectclinical featureen
dc.subjectcomorbidityen
dc.subjectcomputer programen
dc.subjectcopy number variationen
dc.subjectcryptorchismen
dc.subjectdevelopmental disorderen
dc.subjectgene locusen
dc.subjectgenetic analysisen
dc.subjectgenetic associationen
dc.subjectgenetic databaseen
dc.subjectgenetic variabilityen
dc.subjectgenome analysisen
dc.subjectgenomicsen
dc.subjectintegratomicsen
dc.subjectInterneten
dc.subjectmammalen
dc.subjectmolecular pathologyen
dc.subjectmuscle contractionen
dc.subjectonline systemen
dc.subjectorthologyen
dc.subjectprotein expressionen
dc.subjectprotein protein interactionen
dc.subjectproteomicsen
dc.subjectsignal transductionen
dc.subjectsystems biologyen
dc.subjecttranscriptomicsen
dc.subjectCardiomyopathiesen
dc.subjectCluster Analysisen
dc.subjectComputational Biologyen
dc.subjectData Miningen
dc.subjectDatabases, Geneticen
dc.subjectGenetic Locien
dc.subjectInterneten
dc.subjectMetabolic Networks and Pathwaysen
dc.subjectMiceen
dc.subjectMuscle Contractionen
dc.subjectSoftwareen
dc.subjectUser-Computer Interfaceen
dc.subjectAnimaliaen
dc.subjectMammaliaen
dc.titlePivotal role of the muscle-contraction pathway in cryptorchidism and evidence for genomic connections with cardiomyopathy pathways in RASopathiesen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalBMC Medical Genomicsen
dc.identifier.pmcidPMC3626861en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Mechanics, Politecnico di Torino, Turin, Italyen
dc.contributor.institutionProteome Biochemistry Unit, San Raffaele Scientific Institute, Milan, Italyen
dc.contributor.institutionDepartment of Animal Science, Biotechnical Faculty, University of Ljubljana, Domzale, Sloveniaen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorCannistraci, Carloen
kaust.authorRavasi, Timothyen

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