Friday, 28th October 2016
Modelling, Computation and Handling of Data in Health Research
Chairs: Olaf Wolkenhauer, PhD & Rudi Balling, PhD
Professor Dame Janet M Thornton FRS
European Bioinformatics Institute, EMBL-EBI
Wellcome Trust Genome Campus
Cambridge CB10 1SD
Janet Thornton leads a small research group at EMBL-EBI on computational biology. She has published almost 500 scientific papers. See http://www.ebi.ac.uk/research/thornton. The goal of her research is to understand more about how biology works at the molecular level, with a particular focus on proteins, especially enzymes, and their 3D structure and evolution. With her group she explores sequence variation between individuals in different contexts, its relationship to diseases and for different species. To understand more about the molecular basis of ageing in different organisms, the group has a strong collaboration with experimental biologists at UCL, where they analyse functional genomics data from flies, worms and mice and, by developing new software tools, relate these observations to effects on life span.
From 2001-2015 Janet was Director of the European Molecular Biology Laboratory - European Bioinformatics Institute on the Wellcome Trust Genome Campus at Hinxton, near Cambridge, UK. Janet also coordinated the ELIXIR preparatory phase (2006-2013) to build a pan-European infrastructure for life science data. This is now an international infrastructure with 17 member countries.
Exploring Human Variation and its impact on proteins and in the Clinic
Janet Thornton, Roman Laskowski, David Marcus
European Bioinformatics Institute (EMBL-EBI)
Genome sequencing has opened up the possibility of exploring the genetic basis of human evolution and the differences between individuals. Using computational methods and 3D protein structures, we compared disease associated variants with ‘natural’ variants observed in 1000 human genomes, showing significant differences in their distributions. The 100,000 genomes project, funded by the UK government through the NHS, provides a stimulus to bring this new technology into the clinic. This brings both challenges and great opportunities. One of the major challenges is handling the scale and interpreting the complexity of genomic data. This will require a close collaboration between the basic biological and clinical sciences if it is to make a major impact. These challenges will be discussed.
Professor Carole Goble is a Professor of Computer Science at The University of Manchester where she runs a eScience team of computing researchers, scientific informaticians and software engineers. For the past 25 years she has led work on the application of innovations in knowledge management and distributed computing to support scientific discovery. In the 1980s she worked in Medical Informatics and since the 1990s has worked chiefly in the Life Sciences, Biodiversity, Social Sciences and Astronomy. Her technical research interests are in Linked Data and the Semantic Web, Grid and Cloud computing, middleware and repositories. She has pioneered developments in computational workflows, platforms for sharing data, workflows, methods and models, provenance collection, standards efforts and in scholarly communication, publishing over 300 articles. She has developed several open source and widely used systems including Apache Taverna, Open PHACTS, the IMI sponsored Linked Data warehouse for pharmacological data, and the SEEK4Science data and model management system for Systems and Synthetic Biology which forms the basis of the FAIRDOM Platform for FAIR (Findable, Accessible, Interoperable, Reusable) management of Data Operations and Models and is the chief service of the FAIRDOM Community.
Carole is at the heart of EU Research Infrastructures. She is Interim Head of Node for ELIXIR-UK, co-leads the ELIXIR Interoperability workstream and is responsible for the data stewardship for ISBE. She serves on numerous oversight boards including those for the IMI eTRIKS, NIH BDDS and CEDAR Centres and the UK BioBank. She is a member of the UK’s Farr Institute for Public Health data, and is a co-founder and PI of the UK’s Software Sustainability Institute. She serves on the UK’s BBSRC funding agency governing Council.
Over the past 5 years we have seen a change in expectations for the management of all the outcomes of research – that is the “assets” of data, models, codes, SOPs and so forth. Don’t stop reading. Data management isn’t likely to win anyone a Nobel prize. But publications should be supported and accompanied by data, methods, procedures, etc. to assure the reproducibility of results. Funding agencies expect data (and increasingly software) management retention and access plans as part of the proposal process for projects to be funded. Journals are raising their expectations of the availability of data and codes for pre- and post- publication. The multi-component, multi-disciplinary nature of Systems Biology and Systems Medicine demands the interlinking and exchange of assets and the systematic recording of metadata for their interpretation.
The FAIR Guiding Principles for scientific data management and stewardship (http://www.nature.com/articles/sdata201618) has been an effective rallying-cry for EU and USA Research Infrastructures. FAIRDOM (Findable, Accessible, Interoperable, Reusable Data, Operations and Models) Initiative has 8 years of experience of asset sharing and data infrastructure ranging across European programmes (SysMO and EraSysAPP ERANets), national initiatives (de.NBI, German Virtual Liver Network, UK SynBio centres) and PI's labs. It aims to support Systems and Synthetic Biology researchers with data and model management, with an emphasis on standards smuggled in by stealth and sensitivity to asset sharing and credit anxiety. Systems Medicine research adds an extra issue around data privacy. This talk will use the FAIRDOM Initiative to discuss the FAIR management of data, SOPs, and models, highlighting the challenges of and approaches to sharing, credit, citation and asset infrastructures in practice. I'll also highlight recent experiments in affecting sharing using behavioural interventions.
Dr. Hans F. Hoffmann, born in 1942, German nationality, has a PhD in experimental physics from Bonn University/Germany.
As CERN staff from 1972 to 2007 he worked on collider studies and as technical coordinator of the CERN UA1 (discovery W, Z bosons 1983) and ATLAS (discovery Higgs boson 2012) experiments.
He held positions as director of central services (DESY/Hamburg 1985-1989), director of technical support (CERN 1989-1993) and director of technology transfer and scientific computing (CERN 1999-2003), launching the CERN world-wide grid computing.
He was member of the European Science and Technology Assembly, ESTA (1994-1998)
He is now retired and CERN “honorary”, working on UNESCO projects and some CERN project management and knowledge transfer studies.
Since 2012 he is president of ESI, the European Scientific Institute (http://www.esi-archamps.eu/) in France. ESI specialises in thematic schools for Master and PhD students as well as for professionals on accelerators, particle physics instrumentation, medical physics and bio-health computing.
He has published on particle accelerators, detectors, physics results, collaborative engineering, technology transfer, grid computing, e-science, “open access”, translational research management, and knowledge society.
“Federated, curated, simulated data for systems medicine – lessons learned from (particle-) physics”
Hans F. Hoffmann (ESI-Archamps –CERN honorary)
Fundamental, ambitious and complex science projects can attract excellent people and considerable resources. They can achieve even breaking advances in their fields of science if they address the right questions and follow some simple rules of governance.
Particle Physics is a “cosmic” and well organised science operating on a planetary scale. Its scientific infrastructures, collaborating universities, governing principles and common activities are outlined to derive elements of a toolkit to manage complex and ambitious projects.
Some “life sciences” questions, corresponding infrastructures, collaborating university institutes and some novel instruments are presented, all ready to be shared for more encompassing projects such as systems medicine.
CERN LHC, ATLAS, virtual “big science” laboratories, collaboration and competition, open access, PDG, peer reviews, R&D experiments, MoU, “Verbundforschung“, WLCG, ESI Archamps-thematic schools, ESFRI, EU-horizon 2020, EIT-health
Alexander Mazein, Ph.D. in Bioinformatics, University of Edinburgh. He is a researcher in Systems Biology and Medicine at the EISBM, Lyon. Leading the Disease Maps Project: disease-specific comprehensive representation of molecular mechanisms and data interpretation in connection to EU projects funded by IMI (Innovative Medicines Initiative): U-BIOPRED and eTRIKS.
Dr Bertrand De Meulder has obtained his PhD from the University of Namur in Belgium, working on -omics data analysis in cancer and metastasis.
He joined the EISBM three years ago as young researcher in charge of the data integration and handprints generation workflow for the U-BIOPRED project.
11.10 - 11.30 Coffee Break & Exhibition
Doctor and Patient involvement in the era of personalised medicine
Chaires: Prof. Dr. Timothy R.D.J. Radstake
Susanna Palkonen is Director of European Federation of Allergy and Airways Diseases Patients’ Associations (EFA), which brings together 39 member associations from 24 countries to improve the care, environment, participation and equality of people with allergy, asthma and COPD at the European level, including tobacco prevention. As Vice President of the European Patients’ Forum EPF, the umbrella association for 64 European level disease specific patient groups and national platforms of patient associations she is a member European Medicines Agency (EMA) Patient and Consumer Working Party. She is also the patient representative in the Horizon 2020 Scientific Panel for Health.
Rebecca Abma-Schouten is research policy advisor at the Dutch Heart Foundation since 2013. She is responsible for the strategy to stimulate the translation of scientific results to daily practice. Central is the involvement of stakeholders, as patients and doctors, in research (policy) to stimulate and facilitate that research impacts the lives of patients and their beloved ones.
She led the development of the first Dutch cardiovascular research agenda that was co-created with patients, doctors, scientists and the lay public. Over 12.500 people actively contributed. With the development of criteria and initiation of the Committee on Societal Quality she designed and implemented a method to involve users systematically in the evaluation of research. She is also a member of the patient participation workgroup of the Dutch association of medical charities (SGF). Becoming known for her field of expertise, other research organizations involve her in the process of stimulating the societal impact of research. From 2007-2015 she was also affiliated with Leiden University as a part time teacher in Health and Medical Psychology to share her passion for empowering patients to take care of their own health and wellbeing.
Rebecca Abma-Schouten obtained her degree in Health Psychology (cum laude) at Leiden University, the Netherlands (2007). She gained clinical experience in a psychology practice and started working for the Dutch Heart Foundation end 2007. She initiated and led a wide range of innovation projects in cardiovascular health care and science. The strategic involvement of patients and other relevant stakeholders to achieve a project’s goals is her specialty and ‘red thread’ throughout.
Presentation title: Engaging patients in personalizing medicine
Session:Doctor and Patient involvement in the era of personalized medicine
For a health research charity as the Dutch Heart Foundation it is vital to get society engaged with her goals and activities. The Heart Foundation is fully dependent on voluntary donations by Dutch society, often patients and their relatives. But this is not the main reason to get society involved. Engagement of society with research is at least as important and contributes to many facets of science. It can help build public support for and trust in science. It provides new ways to be transparent and accountable to the funders of science. But more substantive: it provides ample opportunities to increase the impact of science on society. This makes involvement of society not only an important endeavor for health charities, but also for individual scientists, research groups and even research communities.
In this presentation a case is discussed to illustrate why and how scientists and research communities, especially in the field of systems medicine, can strategically engage patients and other stakeholders in their work. The case concerns the co-creation of the Dutch cardiovascular research agenda in which over 12.500 people actively contributed. This extensive engagement process resulted in a research agenda with five themes jointly established by patients, doctors, scientists, doctors and lay citizens. After setting the agenda these stakeholders were also actively involved in defining the aims and developing the strategy for each theme and subsequently in the implementation. Their involvement created many opportunities for meaningful collaborations resulting in substantial co-funding and substantive cooperation.
Courtney Coleman is Research Operations Manager at Asthma UK where she leads the charity’s patient involvement activities. This includes involving people with asthma in the Horizon 2020 funded myAirCoach project to improve asthma management through mobile health. Courtney sits on a number of steering committees for active research projects and clinical trials to facilitate patient input.
Marin de Jong, MD, studied medicine at Maastricht University, The Netherlands. In 2013, she started her work as a PhD research fellow at the Department of Gastroenterology of the Maastricht University Medical Centre with a focus on improving care by telemedicine for inflammatory bowel disease patients.
12.45 - 13.30 Lunch & Exhibition
Systems metabolomics and its relation to disease
Chairs: Dr. Charles Auffray, Prof. Dr. Pasquale Innominato
Professor Dr. Ines Thiele studied technical biology at the University of Stuttgart, Germany, and biotechnology at the Ecole supérieure de biotechnologie de Strasbourg, France. In 2009, she earned her PhD in bioinformatics from the University of California, San Diego. In 2009, she joined the Center for Systems Biology at the University of Iceland, as an independent group leader and Assistant Professor. In 2013, she was appointed as Associate Professor for Systems Biomedicine at the University of Luxembourg and received the ATTRACT fellowship from the Fonds National de la Recherche (Luxembourg). In 2015, she was elected as EMBO Young Investigator. Her research aims to improve the understanding on how diet influences human health. Therefore, she uses a computational modeling approach, termed constraint-based modeling, which has gained increasing importance in systems biology. Her group builds comprehensive models of human cells and human-associated microbes; then employs them together with experimental data to investigate how nutrition and genetic predisposition can affect one's health. In particular, she is interested in applying her computational modeling approach for better understanding inherited and neurodegenerative diseases. She is author of numerous international scientific papers and reviewer for multiple journals and funding agencies.
Ines Thiele, PhD
EMBO Young Investigator
Associate Professor in Systems Biomedicine
Head of the Molecular Systems Physiology Group
Project Lead Diagnosis at the National Centre for Excellence in Research in Parkinson’s Disease
Luxembourg Centre for Systems Biomedicine
UNIVERSITY OF LUXEMBOURG
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Dr. Marta Cascante is Full Professor at the Department of Biochemistry and Molecular Biology at University of Barcelona and leader of the Integrative Systems Biology, Metabolomics and Cancer team. She has authored over 200 publications, two of them cited in “Stryer” biochemistry textbook. She is partner of European translational research projects (H2020) in the field of systems medicine and metabolomics and member of the editorial advisory boards of Metabolomics and BMC systems Biology. She has been distinguished in 2015 with Icrea Academia Prize and with the Narcis Monturiol Medal of the Catalan Government for her scientific merits.
Research interests are focused on cancer and metabolic diseases with the goal of elucidating the networks and pathways that are fundamental in their development and progression. More specifically, her team uses a Systems Medicine approach to identify key proteins in the metabolic reprogramming underlying multifactorial diseases, including cancer, to be used as biomarkers or drug targets. In the coming years her team plan to develop a multi-omic approach to construct genome-scale metabolic networks that accurately reflect short-term and long-term metabolic adaptations associated with metastasis and acquired therapeutic resistance. Furthermore, in the framework of H2020 project “PheNoMenal “, coordinated by EBI, her team is contributing to develop and deploy an e-infrastructure that makes it feasible for healthcare researchers to process analyze and mine molecular phenotyping data, to facilitate large-scale data analysis in the coming age of Precision Medicine.
Identification of the metabolic reprogramming underlying metastasis: use and development of PheNoMenal e-infrastructures for analyzing metabolic phenotype data
Marta Cascante1*, Erika Zodda1,2, Esther Aguilar1, Igor Marín de Mas1,3, Silvia Marín1, Vitaly Selivanov1, Fionnuala Morrish3, Mònica Pons2, Inés Izquierdo1, Óscar Meca-Cortés2, Antoni Celià-Terrassa2,Hossain Delowar2, Balázs Papp4, David Hockenbery3,Pedro de Atauri1, Josep J. Centelles1 and Timothy Thomson2
1) Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Diagonal 643, Barcelona 08028, Spain
2) Department of Cell Biology, Molecular Biology Institute, National Research Council (IBMB-CSIC), Barcelona 08028, Spain
3) Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
4) Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Progression towards metastasis is initiated by a cellular process known as epithelial-mesenchymal transition (EMT) and followed by the participation of a minority of malignant cells known as tumor-initiating cells (TICs). Using a well characterized clonal prostate neoplastic cell subpopulations displaying stable and distinct EMT (epithelial-mesenchymal transition) or e-CSCs (metastatic epithelial stem cell) phenotypes, and combining metabolomics, 13C-fluxomics and genome scale metabolic network reconstruction approaches, we have characterized differential key features in their metabolic reprogramming with potential clinical implications. Moreover, analysis of transcriptomic data yielded a metabolic gene signature for our e-CSCs, consistent with the metabolomics and fluxomics analysis that correlated with tumor progression and metastasis in prostate cancer and in 11 additional cancer types, suggesting potential biomarkers and therapeutic targets to effectively forestall metastasis.
Finally, workflow for 13C-fluxomics (in development in the framework of the e-infrastructured project PhenoMeNal www.phenomenal-h2020.eu/home/) to facilitate the use of existing 13C-fluxomics tools and metabolomics data repositories as MetaboLights (www.ebi.ac.uk/metabolights) is also presented.
(Part of these results have been published in Stem Cells 2016;34:1163-1176)
- Spanish Government -MNIC-EuropeanComissionFeder-Una manera de hacer Europa-SAF2014-56059-R
- Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) – Generalitat de Catalunya (2014SGR1017)
- European Comission (H2020-EU.220.127.116.11.- development, deployment and operation of ICT-based e-infrastructures, grant 654241).- PhenoMeNal: A comprehensive and standardised e-infrastructure for analyzing medical metabolic phenotype data.
- Marta Cascante acknowledges the support received through the prize “ICREA Academia” for excellence in research, funded by ICREA foundation – Generalitat de Catalunya
Tanja Cvitanović, PhD student of Biomedicine, University of Ljubljana, Slovenia. She is currently focused on proving the plasticity of the SteatoNet computational model, which describes the dynamics of liver metabolism in interaction with peripheral tissues. Her research aims at the extension of SteatoNet with gender-based differences, thus showing its predictive power.
Dr. Maria Pires Pacheco studied at the University of Luxembourg, from which she recently graduated (2016). She is currently a post-doc in the systems biology group of Professor Thomas Sauter at the University of Luxembourg. Her research aims at the development of algorithms for the generation of context-specific metabolic networks.
15.10 - 15.30 Coffee Break & Exhibition
15.30 - 16.00 Awards, Prizes
Dr. Leroy (Lee) Hood was involved in the development of six instruments critical for contemporary biology, namely the, automated DNA sequencer, DNA synthesizer, protein sequencer, peptide synthesizer, the ink jet printer for constructing DNA arrays and the Nanostring instrument for single molecule nucleic acid detection. These instruments opened the door to high-throughput biological data and the era of big data in biology and medicine. He helped pioneer the human genome program, making it possible with the automated DNA sequencer.
In 1992, Hood created the first cross-disciplinary biology department, Molecular Biotechnology, at the University of Washington. In 2000, he co-founded the Institute for Systems Biology (ISB) in Seattle, the first of its kind, thus pioneering systems medicine. Hood has made many seminal discoveries in the fields of immunology, neurobiology and biotechnology and, most recently, has been a leader in the development of systems biology, its applications to cancer, neurodegenerative disease and the linkage of systems biology to personalized medicine. Hood is now pioneering new approaches to P4 medicine (predictive, preventive, personalized and participatory) and most recently, has embarked on creating a P4 pilot project on 100,000 healthy individuals that is transforming healthcare.
In addition to his ground-breaking research, Hood has published 750 papers, received 36 patents, 17 honorary degrees and more than 100 awards and honors. Hood has founded or co-founded 15 different biotechnology companies including Amgen, Applied Biosystems, Rosetta, Darwin, Integrated Diagnostics, Indi Molecular and Arivale.
Systems Medicine and Proactive P4 Medicine: Transforming Healthcare through Scientific Wellness—A Personal View
Leroy Hood Institute of Systems Biology and Providence Health and Services, Seattle, WA
Systems medicine, the application of systems approaches to disease, places medicine at a fascinating tipping point—promising a revolution in the practice of medicine. I will discuss some of the new systems-driven technologies and strategies that have catalyzed this tipping point. Moreover, four converging thrusts—systems medicine, big/digital data (and its analytics), the digitalization of personal measurements and patient-activated social networks—are leading to a proactive medicine that is predictive, personalized, preventive and participatory (P4). I will contrast P4 medicine with contemporary evidence-based medicine and discuss its societal implications for healthcare. P4 medicine has two central thrusts—quantifying wellness and demystifying disease.
I will discuss our successful effort to introduce P4 medicine into the current healthcare system with a P4 pilot program—a longitudinal, high-dimensional data cloud study on each of 108 well patients over 2014. The preliminary results both with regard to data analyses and patient responses from these studies are striking. They point to the emerging discipline of scientific wellness—and the fact that it will catalyze several new thrusts in healthcare: 1) optimizing wellness, 2) identifying the earliest disease transitions for all common diseases and 3) employing the dense, dynamic, personal data cloud approach to study diseases (e.g. cancer) and their responses to therapy. We started Arivale, a company focused on scientific wellness for the consumer, in 2015 and already have 1200 individuals enrolled. I will also discuss preliminary results from the Arivale studies.
My institute, the Institute for Systems Biology (ISB), has recently affiliated with Providence Health and Systems to become its research arm. Providence is the 3rd largest non-profit healthcare systems in the US—and ISB/Providence will be initiating a series of “translational pillars” moving applications of systems (P4) medicine from the bench to the bedside. These pillars include scientific wellness, bringing scientific wellness to cancer survivors, making Alzheimer’s a reversible and preventive disease, rather than a relentlessly progressive disease, and exploring how the deep, dynamic, personal data clouds can be used to gain a deep understanding of glioblastoma and provide new diagnostic and therapeutic approaches.
Scientific wellness will catalyze a transformation in contemporary healthcare and it will provide tens of thousands of dense, dynamic, personal data clouds that will present striking new opportunities for pharma, biotech, nutrition and diagnostic companies.
Closing of conference