Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/151688
Full metadata record
DC FieldValueLanguage
dc.contributor.authorMarín de Mas, Igor Bartolomé-
dc.contributor.authorTorrents, Laura-
dc.contributor.authorBedia Girbés, Carmen-
dc.contributor.authorNielsen, Lars K.-
dc.contributor.authorCascante i Serratosa, Marta-
dc.contributor.authorTauler Ferré, Romà-
dc.date.accessioned2020-03-02T17:34:47Z-
dc.date.available2020-03-02T17:34:47Z-
dc.date.issued2019-08-15-
dc.identifier.issn1471-2164-
dc.identifier.urihttp://hdl.handle.net/2445/151688-
dc.description.abstractBackground Genome-scale metabolic models (GSMM) integrating transcriptomics have been widely used to study cancer metabolism. This integration is achieved through logical rules that describe the association between genes, proteins, and reactions (GPRs). However, current gene-to-reaction formulation lacks the stoichiometry describing the transcript copies necessary to generate an active catalytic unit, which limits our understanding of how genes modulate metabolism. The present work introduces a new state-of-the-art GPR formulation that considers the stoichiometry of the transcripts (S-GPR). As case of concept, this novel gene-to-reaction formulation was applied to investigate the metabolic effects of the chronic exposure to Aldrin, an endocrine disruptor, on DU145 prostate cancer cells. To this aim we integrated the transcriptomic data from Aldrin-exposed and non-exposed DU145 cells through S-GPR or GPR into a human GSMM by applying different constraint-based-methods. Results Our study revealed a significant improvement of metabolite consumption/production predictions when S-GPRs are implemented. Furthermore, our computational analysis unveiled important alterations in carnitine shuttle and prostaglandine biosynthesis in Aldrin-exposed DU145 cells that is supported by bibliographic evidences of enhanced malignant phenotype. Conclusions The method developed in this work enables a more accurate integration of gene expression data into model-driven methods. Thus, the presented approach is conceptually new and paves the way for more in-depth studies of aberrant cancer metabolism and other diseases with strong metabolic component with important environmental and clinical implications. Electronic supplementary material The online version of this article (10.1186/s12864-019-5979-4) contains supplementary material, which is available to authorized users.-
dc.format.extent12 p.-
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherBioMed Central-
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1186/s12864-019-5979-4-
dc.relation.ispartofBmc Genomics, 2019, vol. 20, num. 1, p. 652-
dc.relation.urihttps://doi.org/10.1186/s12864-019-5979-4-
dc.rightscc-by (c) Marín de Mas, Igor et al., 2019-
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es-
dc.sourceArticles publicats en revistes (Bioquímica i Biomedicina Molecular)-
dc.subject.classificationCàncer de pròstata-
dc.subject.otherProstate cancer-
dc.titleStoichiometric gene-to-reaction associations enhance model-driven analysis performance: Metabolic response to chronic exposure to Aldrin in prostate cancer-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.identifier.idgrec693548-
dc.date.updated2020-03-02T17:34:47Z-
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/320737/EU//CHEMAGEB-
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess-
dc.identifier.pmid31416420-
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

Files in This Item:
File Description SizeFormat 
693548.pdf1.48 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons