6533b82dfe1ef96bd12913db
RESEARCH PRODUCT
Deciphering genomic heterogeneity and the internal composition of tumour activities through a hierarchical factorisation model
David ConesaJoaquín DopazoJosé Carbonell-caballeroAntonio López-quílezsubject
:Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC]Matrix factorisationComputer scienceBioinformaticsGeneral MathematicsSystems biologyPopulationMatrix factorisationContext (language use)Computational biologyComputational biologyGenomic heterogeneitygenomic heterogeneityFactorizationBioinformàticaSimulació per ordinadorComputer Science (miscellaneous)QA1-939cancerVariabilityeducationEngineering (miscellaneous)Topology (chemistry)Cancereducation.field_of_studyvariabilitymatrix factorisationLimitingbioinformaticsCàncer--Aspectes genèticsGenòmicaBreast--CancerTumorigenesisMathematicsdescription
Genomic heterogeneity constitutes one of the most distinctive features of cancer diseases, limiting the efficacy and availability of medical treatments. Tumorigenesis emerges as a strongly stochastic process, producing a variable landscape of genomic configurations. In this context, matrix factorisation techniques represent a suitable approach for modelling such complex patterns of variability. In this work, we present a hierarchical factorisation model conceived from a systems biology point of view. The model integrates the topology of molecular pathways, allowing to simultaneously factorise genes and pathways activity matrices. The protocol was evaluated by using simulations, showing a high degree of accuracy. Furthermore, the analysis with a real cohort of breast cancer patients depicted the internal composition of some of the most relevant altered biological processes in the disease, describing gene and pathway level strategies and their observed combinations in the population of patients. We envision that this kind of approaches will be essential to better understand the hallmarks of cancer. This research was funded by grants PID2020-117979RB-I00 from the Spanish Ministry of Science and Innovation, PT17/0009/0006 from the Instituto de Salud Carlos III (ISCIII), co-funded with European Regional Development Funds (ERDF). Additionally, D.C. and A.L.-Q. would like to thank the Spanish Ministerio de Ciencia e Innovación—Agencia Estatal de Investigación for grant PID2019-106341GB-I00 (jointly financed by the European Regional Development Fund, FEDER). Peer Reviewed
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-11-08 |