Eduard Porta Pardo

Primary tabs

Biography

My long-term goal as a scientist is to understand the relationship between cancer genomics and clinically relevant phenotypes, such as patient outcomes, drug sensitivity and resistance or anti-cancer immune responses. To predict the best treatment for each cancer patient we need to understand the molecular details underlying these clinical features. To do that I use big-data approaches to integrate and analyze various types of biological information, including protein three-dimensional structures, cancer mutation profiles, gene expression data, protein interaction networks or clinical annotations.

The uniqueness of my approach to analyze cancer genomes is that I integrate protein structures with mutation profiles to identify protein regions, not genes, that drive cancer growth, drug sensitivity and immune response. This distinction between genes and protein regions is key because proteins contain different regions that are responsible for different functions. Therefore, it is likely that mutations affecting different protein regions also have distinct contributions to cancer.

I focused my initial research on the identification of cancer driver protein regions. To that end I developed e-Driver, an algorithm that fins protein regions (domains or interaction interfaces) that are enriched in cancer somatic mutations. Using data from The Cancer Genome Atlas I found novel regions that had not been previously linked to cancer, including 20 protein domains and more than 40 protein interaction interfaces. My results have also given novel insights into well-established cancer-driver genes, such as TP53 or EGFR.

I have also applied this sub-gene analysis to identify novel drug biomarkers. I analyzed data from the Cancer Cell Line Encyclopedia (CCLE), a database that contains the genomic profiles of over 500 cancer cell lines as well as their sensitivity towards 24 anti-cancer drugs. My domain-centric analysis with e-Drug found 405 protein domains that are associated with differences in drug sensitivity. As a result of this research, we created a spin-off company, Genrix, that is helping drug companies identify biomarkers for their drug candidates.

My most recent efforts have been in cancer immunology. It is now clear that cancer cells need to avoid the immune system in order to survive, and therapies aimed at restoring the immune response against cancer cells are transforming the landscape of therapies in a way that was unimaginable only a few years ago. I have recently developed an algorithm, domainXplorer, that uses de protein-region analysis philosophy to discover novel cancer immunity drivers. On my analysis of 5000 TCGA samples I discovered over 100 protein regions that, when mutated, correlate with the presence of lymphocytes in the tumor micro-environment.

All the algorithms that I created are posted on my Github account (https://github.com/eduardporta). This also helps to maximize their impact, since they can be used by other researchers for their own projects.

More recently I have contributed to several analysis working groups of the TCGA PanCancer Atlas project. This consortium put together over 1000 scientists in more than 20 countries to jointly analyze the entire TCGA dataset. As a member of the oncogenic processes, driver genes and pan-immunity analysis working groups, I have had the opportunity and privilege to contribute my expertise to this community and help to discover new subtypes of cancer immune responses, expand the catalogue of cancer driver genes and how germline variations interact with somatic mutations in different cancer types.

Education

Degree

University

Year

BSc in Biotechnology

Universitat Autonoma de Barcelona

2008

MSc in Immunology

Universitat de Barcelona

2009

PhD in Biomedicine

Universitat de Barcelona

2013

Mini-MBA

University of California San Diego

2016

Research

First author publications (*co-first author)

  1. Matthew H. Bailey*, Collin Tokheim*, Eduard Porta-Pardo* et.al.. Comprehensive characterization of cancer driver genes and mutations. Cell, 173-2, pp.371-385, 2018

  2. Li Ding*, Matthew H. Bailey*, Eduard Porta-Pardo* et.al.. Perspective on oncogenic processes at the end of the beggining of cancer genomics. Cell, 173-2, pp.305-320, 2018

  3. Eduard Porta-Pardo et.al.. Comparison of algorithms for the detection of cancer drivers at subgene resolution. Nature Methods, 14, pp. 782-788, 2017

  4. Eduard Porta-Pardo and Adam Godzik. Mutation drivers of immunological responses to cancer. Cancer Immunology Research, 4-9, pp. 789-798, 2016

  5. Eduard Porta-Pardo*, Luz Garcia-Alonso*, Thomas Hrabe, Joaquin Dopazo and Adam Godzik. A pan-cancer catalogue of cancer driver protein interaction interfaces. PLoS Computational Biology, 11-10, pp. 1-18, 2015

  6. Eduard Porta-Pardo and Adam Godzik. Analysis of individual protein regions provides novel insights on cancer pharmacogenomics. PLoS Computational Biology, 11-1, pp. 1-9, 2015

  7. Eduard Porta-Pardo*, Thomas Hrabe* and Adam Godzik. Cancer3d: understanding cancer mutations through protein structures. Nucleic Acids Research, 43-D1, pp. 968-973, 2014

  8. Eduard Porta-Pardo and Adam Godzik. e-Driver: a novel method to identify protein regions driving cancer. Bioinformatics, 30-21, pp. 3109-3114, 2014


 

Publications with other contributions

  1. Vesteinn Thorsson, David L Gibbs, Scott D Brown, Denise Wolf, Dante S Bortone, Tai-Hsien Ou Yang, Eduard Porta-Pardo et.al.. The immune landscape of cancer. Immunity, 48-4, pp.812-830, 2018

  2. Hector Climente-Gonzalez, Eduard Porta-Pardo, Adam Godzik and Eduardo Eyras. The functional impact of alternative splicing in cancer. Cell Reports, 20-9, pp. 2215-2226, 2017

  1. Roger Colobran, Mireia Gimenez-Barcons, Ana Marin-Sanchez, Eduard Porta-Pardo and Ricardo Pujol Borrell. AIRE genetic variants and predisposition to polygenic autoimmune disease: The case of Graves’ disease and a systematic literature review. Human immunology, 77-8, pp. 643-651, 2016

  2. Mireia Gimenez-Barcons, Anna Casteras, Maria del Pilar Armengol, Eduard Porta-Pardo, Paula Correa, Ana Marin-Sanchez and Ricardo Pujol Borrell. Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens. The Journal of Immunology, 193-8, pp. 3872-3879, 2014

  3. Roger Colobran, Maria del Pilar Armengol, Eduard Porta-Pardo, Paula Correa and Ricardo Pujol Borrell. Decreased AIRE and promiscuous gene expression in thymus from Down syndrome individuals may explain predisposition to autoimmunity. Journal of Translational Medicine, 10-3, pp. 5-5, 2012