P5A STEPHAN OSSOWSKI, CENTRE REGULACIÓ GENÒMICA – CRG, SPAIN
Xavier Estivill and Stephan Ossowski are both integrated at the Bioinformatics and Genomics program at the CRG. The CRG has a powerful scientific computing network and a Bioinformatics core facility.
CRG, Centre for Genomic Regulation: The Centre for Genomic Regulation (www.crg.eu) is an interdisciplinary biomedical research institute of excellence located in the Barcelona Biomedical Research Park (PRBB, www.prbb.cat). The CRG is legally constituted as a non-profit research foundation, which has the participation from the Catalan Government through the Economy and Knowledge Department (DECO) and the Health Department (DS), and the Spanish Ministry of Economy & Competitiveness (MINECO), and it is affiliated with the Pompeu Fabra University (UPF).
Research at the CRG is currently organized in four research programs, led by outstanding international scientists, and cutting-edge core facilities, which include bioinformatics, proteomics, high- throughput screening, and genomics. Several high-throughput technologies have been implemented at the genomics unit (expression, genetic variation, microRNA discovery, sequencing, epigenetic profiling, and identification of binding sites of DNA or RNA-associated proteins).
The scientific excellence is underlined by the outstanding publication record (9th worldwide in the health sector, according to Q1 indicator in the 2013 Scimago Institutions Ranking report 2007-2011), the quality of its international staff (65% of the PI and 78% of the PhD students are foreigners) and the successful external funding record (13 ERC, 42 active FP7 projects, 6 of which coordinated by CRG PIs, 70 in total in FP7). CRG is one of 18 Spanish research centres of excellence awarded with a highly competitive ‘Severo Ochoa’ grant. In addition, in 2013 the CRG was awarded the HR Excellence logo by the European Commission to recognize the institute’s commitment to improve human resources policies for researchers.
The Bioinformatics and Genomics program at the CRG addresses the specific needs in data acquisition, storage, analysis and integration that research in genomics generates. Eight independent, leading, research groups are part of this program, including the EGA European Genome-Phenome archive at the CRG, and the Genomics and disease group. The Bioinformatics and Genomics program has a computing cluster which provides sufficient computing power and storage space for the project.
P5A STEPHAN OSSOWSKI, CENTRE REGULACIÓ GENÒMICA – CRG, SPAIN
The Genomics and Epigenomic Variation in Disease group lead by Stephan Ossowski is developing methods for computational genomics and epigenomics, with a strong focus on approaches for next generation sequencing (NGS) analysis with applications in medical genomics research and clinical diagnostics. The group has implemented algorithms for variant identification and prioritization in rare and familial disease studies as well as in large-scale cancer studies. The expertise in computational NGS- based analysis of personal genomes has been translated into a computational platform for clinical diagnostics, which has previously been applied to identify causal variants in diseases like ataxi, masthenia, cystic fibrosis and hyperkalemia. As part of the ICGC-CLL and PCAWG consortia the group has developed methods for identification of driver genes, heterogeneous somatic copy number alterations as well as somatic indels. As a complementary field of activity the group is developing wet-lab and computational approaches to study the epigenome of healthy and disease tissue, with a focus on identification of changes in regulatory activity caused by genetic or epigenetic variability. With eight computational biologists the group has a strong bioinformatics expertise, but also maintains the expertise to implement novel types of NGS experiments independantly. The group participates in other consortia, such as BLUEPRINT/IHEC, GEUVADIS and EUPancreas.
WP1: P5a will lead the development of a distributed and cloud-enabled platform for NGS-based analysis in either large-scale cancer risk discovery studies or in small and large-scale cancer screening programs in the clinics. This includes benchmarking of existing methods for distributed data storage and analysis, the benchmarking and integration of basic NGS tools and the adaptation of the pipeline to Amzaon AWS. P5a will organize training sessions on the use of the diagnostics software for clinical personnel. Furthermore P5a will develop methods and filters for optimal (batch effect free) variant calling across different cancer and control cohorts and perform the analysis of ICGC/TCGA cancer genomes at CRG (8,000 total WES samples will be analysed in a distributed fashion on CRG and EBI compute clusters).
WP2: P5a will participate in the analysis of rare variant enrichments in genes and protein- interaction networks, with a specific focus on the selection of small and highly interacting sub- networks of proteins from String-DB using co-expression analysis and the optimization of mixed effect models for PPIs.
WP3: P5a will participate in the development of regulatory region and regulatory variant predictors using machine learning approaches and the integration of different classifiers (existing and novel) using an ensemble classifier method. P5a will participate in the generation of a reference regulatory region set for tissues affected by PCAWG cancer as well as a set of candidate regulatory variants potentially associated to cancer risk, which will be functionally validate in WP5.
WP4: P5a will contribute to the selection of candidate risk genes and variants for designing the MGTS panel.
WP5: P5a will contribute to the selection of regulatory variants for functional analysis.
Stephan Ossowski (male, PhD) graduated in Computer Science in 2004 and received his doctorate degree in Computational Biology from the Max Planck Institute and the University of Tübingen, Germany in 2010. He specializes in algorithm development for biological sequence analysis and machine learning methods for the analysis of complex genomics and epigenomics data. He is a Junior Group Leader at the Centre for Genomic Regulation (CRG), heading the Genomics and Epigenomics Variation in disease group. Stephan Ossowski has participated in several EC projects.
Stephan Ossowski has extensive experience in the computational analysis of NGS data for studying the genome of model organisms as well as for uncovering genomic loci associated to genetic diseases and cancer. He has published the first NGS-based analysis of a complete plant genome (A. thaliana) in 2008 and has developed several open-source tools for NGS analysis freely available on sourceforge and bioinformatics related websites (e.g. http://www.geuvadis.org/geevs and http://wmd3.weigelworld.org/). He participates in the ICGC-CLL analysis, the PanCancer project PCAWG to characterize over 2,000 cancer genomes (work packages 8 – germline cancer genome and 6 – structural variants), and the EUPancreas initiative.
Oliver Drechsel (male, PhD). Post-Doctoral Research Fellow and responsible for the analysis of ICGC- CLL and PCAWG data, as well as main developer of the eDiVA analysis platform for NGS based identification of causal variants in genetic disease. Oliver is a biochemist (MSc.) with extensive experience in sequence bioinformatics, high-performance computing, next generation sequencing and genetic diseases.
Hana Susak (female, MSc. Computer Science). PhD Fellow and responsible for the development of a novel rare variants exome-wide association study (REWAS) method and has implemented a Bayesian method for identification of driver genes in heterogeneous tumours. Hana is a computer scientist with an extensive background in biostatistics and experience in next generation sequencing analysis.
Shalu Jhanwar (female, MSc. Bioinformatics). PhD Fellow and responsible for the development of methods for computational epigenomics, including analysis tools for bisulfite-sequencing and ATAC-seq data as well as machine learning approaches for identification of regulatory regions using epigenomic data. Shalu is a bioinformatician with an extensive background in programming, NGS analysis and epigenomics.
Luis Zapata (male, MSc. Bioinformatics). PhD Fellow and responsible for the development of a genome de novo assembly pipeline, a Bayesian method for identification of driver genes in heterogeneous tumours and a predictor of somatic CNVs in heterogeneous tumours. Luis is a bioinformatician with a strong background in programming, large-scale data analysis, genetics and tumour evolution.
Mattia Bosio (male, PhD). Post-Doctoral Research Fellow and responsible for the analysis of PCAWG data, as well as main developer of the eDiVA analysis platform for NGS based identification of causal variants in genetic disease. Mattia is a Telecommunications engineer (MSc.) with extensive experience in sequence bioinformatics, high-performance computing, machine learning applied to next generation sequencing data.
The aims in WP1 and WP2 require a dedicated software engineer to deliver high-quality implementations of the proposed algorithms. One scientific programmer will be recruited solely from EC funding. For WP2 and WP3 we will recruit one additional postdoctoral fellow to develop novel risk gene association methods and machine learning modules for regulatory variant identification. The fellow will be solely paid from EC funding.
P5B XAVIER ESTIVILL, GENOMICS AND DISEASE GROUP – CRG
The Genomics and Disease group, lead by Xavier Estivill, is applying genomic-centric approaches to reveal the genetic basis of complex and rare diseases. The group of Xavier Estivill has set up several techniques to study genetic variants, epigenetic modifications and non-coding RNA biology, including genomic approaches and high-throughput sequencing for characterization of the exome and transcriptome. Excellent bioinformatics expertise is available, with outstanding approaches and pipelines for the analysis of genomic and transcriptomic data. The lab has set up and validated a unique methodology and set of tools to study small RNA biogenesis. Xavier Estivill has coordinated the GEUVADIS project, funded by the EC, which that has harmonized research in the study of genetic variability in human diseasewith specific activities in RNA and exome sequencing. The project has lead to landmark publications in Nature and Nature Biotechnology and over 40 other scientific papers. The group participates in other consortia, such as BLUEPRINT, ESGI, ICGC, and IRDiRC.
WP1: P5b will participate in the development of several tools for the characterisation of cancer genomes at the level of structural variants and in the integration of several bioinformatics pipelines for clinical applications in the analysis of germline and genetics predisposition to cancer in the PCAWG project.
WP2: P5b will participate in the analysis rare variants in biological pathways or protein- interaction networks, which is expected to provide statistical power for detection of small genetic effects. Rare variant association analysis using gene burden, sequence kernel association, and an integrative mixed effect model test, will be performed to identify the cancer predisposition genes and variants in the PCAWG project.
WP4: P5b will participate in targeted resequencing to replicate the findings of WGS and WES of the PCAWG project exome sequencing in breast cancer and colorectal cancer samples using MGTS panels. P5b will participate in the clinical validation using genotyping and MGTS panels of patients tested in breast cancer and colorectal cancer screening programs.
WP5: P5b will contribute to the selection of variants for functional analysis, in particular those that will combine in patients that develop breast or colorectal cancer.
Xavier Estivill has extensive experience in the analysis of complex genetic disorders and cancer. He has participated in the ICGC for CLL analysis, and now co-leads with Jan Korbel the germline working group of the PanCancer project to characterize over 2,000 cancer genomes.
Xavier Estivill (male MD, PhD). Graduated and doctorate in Medicine, and specialised in Haematology, by the Autonomous University of Barcelona, and doctorate in Philosophy by the University of London. He is Senior Group Leader at the Centre Genomic Regulation (CRG), Associate Professor of the Pompeu Fabra University (UPF), and Director of the Genomics and Personalized Medicine section of the Quiron- Dexeus University Hospital in Barcelona. Xavier Estivill has participated and coordinated several EC projects.
Raquel Rabionet (female, PhD). Senior Technician and responsible for genomics sequencing analysis in the group. Geneticist with extensive experience in the association analysis of complex disorders and in next generation sequencing analysis, with >40 published papers, including first and last author publications.
Georgia Escaramís (female, PhD). Post-Doctoral Research Fellow, published >50 papers. Statistician with extensive experience in the analysis of next generation sequencing, genetics epidemiology and statistical modelling in association studies. Has developed several pipelines for exome sequencing analysis.
Aparna Prassad (female, PhD). Post-Doctoral Research Fellow. Geneticist large experience in the analysis of structural variants in relation autism and other neurodevelopmental disorders. She has performed extensive analysis of CLL and other haematological cancers applying new approaches for rare variants.
