Objectif The overarching goal of the proposal presented here is the use of massively parallel sequencing for the identification of novel genetic and epigenetic factors playing role in RNA processing. Specifically, we plan to focus on the role of long non-coding RNAs and histone modifications in splicing regulation during cell differentiation. Towards that end, we plan to monitor RNA and chromatin changes across many time points through RNASeq and ChIPSeq in two cell differentiation models: 1) the induced transdifferentiation of human pre-B cells into macrophages, and 2) organ morphogenesis during fly development. By investigating, through these time course experiments, patterns of molecular co-variation—for instance, between inclusion levels of alternative exons and histone modifications—we can learn how these factors participate, and eventually cooperate, to modulate the condition specific abundance of the alternative splice forms. We plan therefore to develop statistical methods to infer significant patterns of molecular co-variation through the analysis of datasets profiling RNA and chromatin structure across many data points. Based on these findings, we plan to develop a mathematical model of splicing in which the relative abundance of alternative splice forms is predicted from the relevant genetic and epigenetic factors. To facilitate the storage, organization, access, and analysis of the data produced through the project we propose to develop a robust, efficient, and scalable software system. The system will be open source, so that it can be used and enhanced by other researchers. Realizing that the current model for the storage of publicly available biomolecular data, based on centralized repositories, may not be longer sustainable, we will design our software system assuming a peer-to-peer like network of distributed RNASeq data and resources, across which bioinformatics analyses will be transparently performed. Champ scientifique natural sciencescomputer and information sciencessoftwaresoftware applicationssystem softwarenatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticsepigeneticsnatural sciencesmathematicsapplied mathematicsmathematical model Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS2 - ERC Advanced Grant - Genetics, Genomics, Bioinformatics and Systems Biology Appel à propositions ERC-2011-ADG_20110310 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil FUNDACIO CENTRE DE REGULACIO GENOMICA Contribution de l’UE € 2 056 638,00 Adresse CARRER DOCTOR AIGUADER 88 08003 Barcelona Espagne Voir sur la carte Région Este Cataluña Barcelona Type d’activité Research Organisations Chercheur principal Roderic Guigó (Dr.) Contact administratif Olga Juderias (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire FUNDACIO CENTRE DE REGULACIO GENOMICA Espagne Contribution de l’UE € 2 056 638,00 Adresse CARRER DOCTOR AIGUADER 88 08003 Barcelona Voir sur la carte Région Este Cataluña Barcelona Type d’activité Research Organisations Chercheur principal Roderic Guigó (Dr.) Contact administratif Olga Juderias (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
