From biomarkers to disease mechanisms in the transition to precision medicine


From biomarkers to disease mechanisms in the transition to precision medicine

by Prof. Dr. Joaquín Dopazo

Abstract: Precision medicine aims to find better ways of defining diseases by gradually substituting conventional pathological diagnostic criteria with state-of-the-art molecular profiling methodologies. More precise diagnostic of diseases is facilitated by the use of increasingly cheaper and more precise sequencing technologies that enables the discovery of new biomarkers by statistical association of phenotypes to genomic variants.

However, the real transition to a true precision medicine, in which diagnostic, prognostic and treatment decisions are based on knowledge and not in a pure statistical association, requires of a deeper, systems-based understanding of both disease drivers and drug mechanisms of action. Here I will discuss how primary gene expression and gene variation data can be integrated and transformed into mechanism-based biomarkers containing higher-level information on disease mechanisms or drug modes of action by means of relatively simple models of functional pathways. Such modeling framework opens the possibility of suggesting knowledge-based interventions for specific individual patients and constitutes a paradigm of real precision medicine that will foster the advent of innovative diagnostic, prognostic, and therapeutic strategies precisely tailored to each patient’s requirements.

Bio: Joaquín Dopazo obtained his PhD in Biology at the University of Valencia in 1989. After several appointments in different research centers and companies he worked for 5 years in GlaxoWellcome (now Glaxo SmithKline) during the late nineties. There he was in charge of the Bioinformatics unit of the Spanish node, developing methods for bacterial genomic analysis and he participated in several bacterial and fungal genome sequencing projects. In particular, Dr. Dopazo coordinated the assembly and annotation of the bacterial pathogen Streptococcus pneumoniae (Dopazo, 2001, Micr. Drug Res.). In 2000 he moved to the Spanish National Cancer Center (CNIO), where he set up the Bioinformatics group. In the CNIO he coordinated the design of the first Spanish microarray (the Oncochip) in 2000 and he developed the one of the most used resources for transcriptome data analysis and interpretation on the web, the Babelomics (, cited more than 2000 times). In 2005 Dr. Dopazo moved to the CIPF (Valencia) where he set up the Department of Computational Genomics (formerly Bioinformatics). He served as scientific director of the Center during 2012. In 2017 He moved to the Clinical Bioinformatics Research Area from the Fundación Progreso y Salud, In Sevilla, where he coordinates, within the Andalusian Personalized Medicine Program, the introduction of genomic data in the patient electronic health record (eHR). In addition, he heads the Bioinformatics node (BiER) of the CIBERER, where he coordinates a pilot project with seven hospitals across Spain to collect patient genomic data with advanced software of variant prioritization ( He also heads the node of functional genomics of the Spanish National Institute of Bioinformatics. The scope of his research has evolved in parallel to the introduction of “Big Data” in the life sciences. He has been working on genomic data integration and, specifically, during the last years, focusing on massive sequence data analysis. As an example of the impact of the developments of Dopazo’s group, the software GenomeMaps (, has been chosen as the genome viewer of the International Cancer Genome Consortium data analysis portal ( Dr. Dopazo’s scientific interests revolve around functional genomics, systems biology and development of algorithms and software for the analysis of high-throughput data (mainly, but not restricted to, Next Generation Sequencing) and its application to personalized and precision medicine. He is particularly interested in studying disease mechanisms and drug action mechanisms by modeling complex cellular systems in which signaling, regulation and metabolism knowledge are integrated (see an example with He has promoted and coordinated genomic projects such as the FutureClinic (, to prepare the scenario for the introduction of the genome in the eHR, or the Medical Genome Project (, that sequenced over 1000 patients of inherited diseases to search for new biomarkers and disease genes. He was also involved in international projects such as the MAQC and SEQC (best practices in the use of microarrays and NGS, respectively, for finding diagnostic biomarkers), the START consortium to characterize the variability of the rat genome or the Citrus Genome (Wu et al. Nature, 2018).

Keynote date: TBA