Obiettivo Owing to advances in sequencing technology, we are now beginning to understand the molecular mechanisms underlying cancer development and evolution. Tumours however are heterogeneous, often containing admixed normal cells and different (sub)clones, confounding interpretation of the massive amounts of data flowing from large initiatives such as the International Cancer Genome Consortium.To address this issue, I will develop methods that disentangle tumour bulk gene expression (RNA-Seq) and DNA methylation (Bisulphite-Seq) data to accurately reveal the states of the distinct underlying cell populations. The innovative algorithms will derive estimates of the allele-specific expression/methylation rates and tumour copy number profiles from the data and use them to separate the signal coming from the tumour from that of the normal cells. In a second step, the method leverages the wealth of available cancer ‘omics data using a recommender-system approach to complete the deconvolution. Careful validation will come from teasing apart computationally mixed pure samples as well as from ongoing and planned collaborative single-cell sequencing projects. A detailed analysis of tumour expression and DNA methylation heterogeneity on these single-cell datasets will guide further methodological advances. As an intrinsic part of the project, massive pan-cancer datasets will be deconvoluted. Drawing on the pure transcriptomes and epigenomes, I will construct a more comprehensive taxonomy of cancers, laying the basis for significant improvements in clinical prognostic prediction and personalised treatment.This project will shift the paradigm of genomic tumour heterogeneity to include the more actionable transcriptome and epigenome. In turn this will lead to a better understanding of how (epi)genomic alterations translate into the transcriptomic (and proteomic, interactomic, …) changes driving cancer evolution. Campo scientifico natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncology Programma(i) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Argomento(i) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Invito a presentare proposte H2020-MSCA-IF-2015 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF-EF-ST - Standard EF Coordinatore THE FRANCIS CRICK INSTITUTE LIMITED Contribution nette de l'UE € 195 454,80 Indirizzo 1 MIDLAND ROAD NW1 1AT London Regno Unito Mostra sulla mappa Regione London Inner London — West Camden and City of London Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 195 454,80