Functional Effects Detailed Research Plan
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Department of Medical Sciences
Department of Medical Sciences Annual Report 2013 Fastställd av Eva Tiensuu Jansson 2013-05-09 1 Introduction Following the trend from recent years, 2013 was also a positive year for the Department of Medical Sciences. The Department has continued to grow, both in staff and in revenues. The staff are now 210, and the Department has more than 300 associated co-workers at the Uppsala University Hospital, working in more than 20 different clinical specialities. The revenues increased with 5 % to 244 MSEK, which can be attributed to the ability of the researchers at the Department to attract grants from e.g. the Swedish Research council, the Cancer Society, the Swedish Heart&Lung Fondation and from the EU, from which for example professor Erik Ingelsson was awarded the prestigious ERC starting grant. Last year professor Lars Rönnblom together with coinvestigators also were awarded 28 million SEK from AstraZeneca/SciLife for a five-year project aiming to dissect disease mechanisms in three systemic inflammatory autoimmune diseases with an interferon signature. In this context I also would like to mention the excellent services provided by the platforms hosted by the Department; the SNP&SEQ Technology platform and the Array and Analysis facility. The performance of the Department's research groups is also shown by the close to 600 peer reviewed publications during 2013, an increase with 10% from 2012, and by the 14 theses produced during 2013. The theses presented represent all six research programs at the Department, namely Cancer, Cardiology and Clinical physiology, Diabetes and Metabolic Diseases, Epidemiology, Inflammation and autoimmunity, and Microbiology and Infectious diseases. -
Improving the Prediction of Transcription Factor Binding Sites To
Improving the prediction of transcription factor binding sites to aid the interpretation of non-coding single nucleotide variants. Narayan Jayaram Research Department of Structural and Molecular Biology University College London A thesis submitted to University College London for the degree of Doctor of Philosophy 1 Declaration I, Narayan Jayaram confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Narayan Jayaram 2 Abstract Single nucleotide variants (SNVs) that occur in transcription factor binding sites (TFBSs) can disrupt the binding of transcription factors and alter gene expression which can cause inherited diseases and act as driver SNVs in cancer. The identification of SNVs in TFBSs has historically been challenging given the limited number of experimentally characterised TFBSs. The recent ENCODE project has resulted in the availability of ChIP-Seq data that provides genome wide sets of regions bound by transcription factors. These data have the potential to improve the identification of SNVs in TFBSs. However, as the ChIP-Seq data identify a broader range of DNA in which a transcription factor binds, computational prediction is required to identify the precise TFBS. Prediction of TFBSs involves scanning a DNA sequence with a Position Weight Matrix (PWM) using a pattern matching tool. This thesis focusses on the prediction of TFBSs by: (a) evaluating a set of locally-installable pattern-matching tools and identifying the best performing tool (FIMO), (b) using the ENCODE ChIP-Seq data to evaluate a set of de novo motif discovery tools that are used to derive PWMs which can handle large volumes of data, (c) identifying the best performing tool (rGADEM), (d) using rGADEM to generate a set of PWMs from the ENCODE ChIP-Seq data and (e) by finally checking that the selection of the best pattern matching tool is not unduly influenced by the choice of PWMs. -
Applied Category Theory for Genomics – an Initiative
Applied Category Theory for Genomics { An Initiative Yanying Wu1,2 1Centre for Neural Circuits and Behaviour, University of Oxford, UK 2Department of Physiology, Anatomy and Genetics, University of Oxford, UK 06 Sept, 2020 Abstract The ultimate secret of all lives on earth is hidden in their genomes { a totality of DNA sequences. We currently know the whole genome sequence of many organisms, while our understanding of the genome architecture on a systematic level remains rudimentary. Applied category theory opens a promising way to integrate the humongous amount of heterogeneous informations in genomics, to advance our knowledge regarding genome organization, and to provide us with a deep and holistic view of our own genomes. In this work we explain why applied category theory carries such a hope, and we move on to show how it could actually do so, albeit in baby steps. The manuscript intends to be readable to both mathematicians and biologists, therefore no prior knowledge is required from either side. arXiv:2009.02822v1 [q-bio.GN] 6 Sep 2020 1 Introduction DNA, the genetic material of all living beings on this planet, holds the secret of life. The complete set of DNA sequences in an organism constitutes its genome { the blueprint and instruction manual of that organism, be it a human or fly [1]. Therefore, genomics, which studies the contents and meaning of genomes, has been standing in the central stage of scientific research since its birth. The twentieth century witnessed three milestones of genomics research [1]. It began with the discovery of Mendel's laws of inheritance [2], sparked a climax in the middle with the reveal of DNA double helix structure [3], and ended with the accomplishment of a first draft of complete human genome sequences [4]. -
A Community Proposal to Integrate Structural
F1000Research 2020, 9(ELIXIR):278 Last updated: 11 JUN 2020 OPINION ARTICLE A community proposal to integrate structural bioinformatics activities in ELIXIR (3D-Bioinfo Community) [version 1; peer review: 1 approved, 3 approved with reservations] Christine Orengo1, Sameer Velankar2, Shoshana Wodak3, Vincent Zoete4, Alexandre M.J.J. Bonvin 5, Arne Elofsson 6, K. Anton Feenstra 7, Dietland L. Gerloff8, Thomas Hamelryck9, John M. Hancock 10, Manuela Helmer-Citterich11, Adam Hospital12, Modesto Orozco12, Anastassis Perrakis 13, Matthias Rarey14, Claudio Soares15, Joel L. Sussman16, Janet M. Thornton17, Pierre Tuffery 18, Gabor Tusnady19, Rikkert Wierenga20, Tiina Salminen21, Bohdan Schneider 22 1Structural and Molecular Biology Department, University College, London, UK 2Protein Data Bank in Europe, European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, CB10 1SD, UK 3VIB-VUB Center for Structural Biology, Brussels, Belgium 4Department of Oncology, Lausanne University, Swiss Institute of Bioinformatics, Lausanne, Switzerland 5Bijvoet Center, Faculty of Science – Chemistry, Utrecht University, Utrecht, 3584CH, The Netherlands 6Science for Life Laboratory, Stockholm University, Solna, S-17121, Sweden 7Dept. Computer Science, Center for Integrative Bioinformatics VU (IBIVU), Vrije Universiteit, Amsterdam, 1081 HV, The Netherlands 8Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, L-4367, Luxembourg 9Bioinformatics center, Department of Biology, University of Copenhagen, Copenhagen, DK-2200, -
Gene Prediction: the End of the Beginning Comment Colin Semple
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central http://genomebiology.com/2000/1/2/reports/4012.1 Meeting report Gene prediction: the end of the beginning comment Colin Semple Address: Department of Medical Sciences, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. E-mail: [email protected] Published: 28 July 2000 reviews Genome Biology 2000, 1(2):reports4012.1–4012.3 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2000/1/2/reports/4012 © GenomeBiology.com (Print ISSN 1465-6906; Online ISSN 1465-6914) Reducing genomes to genes reports A report from the conference entitled Genome Based Gene All ab initio gene prediction programs have to balance sensi- Structure Determination, Hinxton, UK, 1-2 June, 2000, tivity against accuracy. It is often only possible to detect all organised by the European Bioinformatics Institute (EBI). the real exons present in a sequence at the expense of detect- ing many false ones. Alternatively, one may accept only pre- dictions scoring above a more stringent threshold but lose The draft sequence of the human genome will become avail- those real exons that have lower scores. The trick is to try and able later this year. For some time now it has been accepted increase accuracy without any large loss of sensitivity; this deposited research that this will mark a beginning rather than an end. A vast can be done by comparing the prediction with additional, amount of work will remain to be done, from detailing independent evidence. -
SD Gross BFI0403
Janet Thornton Bioinformatician avant la lettre Michael Gross B ioinformatics is very much a buzzword of our time, with new courses and institutes dedicated to it sprouting up almost everywhere. Most significantly, the flood of genome data has raised the gen- eral awareness of the need to deve-lop new computational approaches to make sense of all the raw information collected. Professor Janet Thornton, the current director of the European Bioinformatics Institute (EBI), an EMBL outpost based at the Hinxton campus near Cambridge, has been in the field even before there was a word for it. Coming to structural biology with a physics degree from the University of Nottingham, she was already involved with computer-generated structural im- ages in the 1970s, when personal comput- ers and user-friendly programs had yet to be invented. The Early Years larities. Within 15 minutes, the software From there to the EBI, her remarkable Janet Thornton can check all 2.4 billion possible re- career appears to be organised in lationships and pick the ones relevant decades. During the 1970s, she did doc- software to compare structures to each to the question at hand. In comparison toral and post-doctoral research at other, recognise known folds and spot to publicly available bioinformatics the Molecular Biophysics Laboratory in new ones. Such work provides both packages such as Blast or Psiblast, Oxford and at the National Institute for fundamental insights into the workings Biopendium can provide an additional Medical Research in Mill Hill, near Lon- of evolution on a molecular level, and 30 % of annotation, according to Inphar- don. -
100000 Genomes and Genomics England
100,000 Genomes & Genomics England Tim Hubbard Genomics England King’s College London, King’s Health Partners Wellcome Trust Sanger Institute Global Leaders in Genomic Medicine Washington 8-9th January 2014 UK Health System 101 • Four separate health services – NHS England – NHS Wales – NHS Scotland – Health & Social Care in Northern Ireland (HSC) • NHS (England) – ~1.4 million employees – ~£110 billion annual budget • Structure in England changed 1st April 2013 https://www.gov.uk/government/organisations/department-of-health Linking Health data to Research Clinical Data Healthcare Professional World Genotype Electronic Health Record Whole Genome Sequencing Phenotype Electronic Genomic Biology Health Data World Records Reference Genotype and genome sequence Phenotype ~3 gigabytes relationship capture EBI: repositories (petabytes of genome sequence data) Human sequence data Sanger: sequencing repositories (1000 genomes, uk10K) Steps in UK towards E-Health Research, Genomic Medicine • Health data to Research – 2006 Creation of OSCHR • Increase coordination between funders: MRC and NIHR – 2007 OSCHR E-health board • Enable research access to UK EHR data • Build capacity for research on EHR data • Genomics to Health – 2009 House of Lords report on Genomic Medicine – 2010 Creation of Human Genomic Strategy Group (HGSG) 2011: UK Life Sciences Strategy No10: http://www.number10.gov.uk/news/uk-life-sciences-get-government-cash-boost/ BIS/DH: http://www.dh.gov.uk/health/2011/12/nhs-adopting-innovation/ Linking Health data to Research Clinical Data -
Predicting and Characterising Protein-Protein Complexes
Predicting and Characterising Protein-Protein Complexes Iain Hervé Moal June 2011 Biomolecular Modelling Laboratory, Cancer Research UK London Research Institute and Department of Biochemistry and Molecular Biology, University College London A thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Biochemistry at the University College London. 2 I, Iain Hervé Moal, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Abstract Macromolecular interactions play a key role in all life processes. The con- struction and annotation of protein interaction networks is pivotal for the understanding of these processes, and how their perturbation leads to dis- ease. However the extent of the human interactome and the limitations of the experimental techniques which can be brought to bear upon it necessit- ate theoretical approaches. Presented here are computational investigations into the interactions between biological macromolecules, focusing on the structural prediction of interactions, docking, and their kinetic and thermo- dynamic characterisation via empirical functions. Firstly, the use of normal modes in docking is investigated. Vibrational analysis of proteins are shown to indicate the motions which proteins are intrinsically disposed to under- take, and the use of this information to model flexible deformations upon protein-protein binding is evaluated. Subsequently SwarmDock, a docking algorithm which models flexibility as a linear combination of normal modes, is presented and benchmarked on a wide variety of test cases. This algorithm utilises state of the art energy functions and metaheuristics to navigate the free energy landscape. -
The EMBL-European Bioinformatics Institute the Hub for Bioinformatics in Europe
The EMBL-European Bioinformatics Institute The hub for bioinformatics in Europe Blaise T.F. Alako, PhD [email protected] www.ebi.ac.uk What is EMBL-EBI? • Part of the European Molecular Biology Laboratory • International, non-profit research institute • Europe’s hub for biological data, services and research The European Molecular Biology Laboratory Heidelberg Hamburg Hinxton, Cambridge Basic research Structural biology Bioinformatics Administration Grenoble Monterotondo, Rome EMBO EMBL staff: 1500 people Structural biology Mouse biology >60 nationalities EMBL member states Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom Associate member state: Australia Who we are ~500 members of staff ~400 work in services & support >53 nationalities ~120 focus on basic research EMBL-EBI’s mission • Provide freely available data and bioinformatics services to all facets of the scientific community in ways that promote scientific progress • Contribute to the advancement of biology through basic investigator-driven research in bioinformatics • Provide advanced bioinformatics training to scientists at all levels, from PhD students to independent investigators • Help disseminate cutting-edge technologies to industry • Coordinate biological data provision throughout Europe Services Data and tools for molecular life science www.ebi.ac.uk/services Browse our services 9 What services do we provide? Labs around the -
Genomics England and Sciencewise Evaluation of a Public Dialogue On
Genomics England and Sciencewise Evaluation of a public dialogue on Genomic Medicine: Time for a new social contract? Evaluation report June 2019 Quality Management URSUS Consulting Ltd has quality systems which have been assessed and approved to BS EN IS9001:2008 (certificate number GB2002687). Creation / Revision History Issue / revision: 3 Date: 19/6/2019 Prepared by: Anna MacGillivray Authorised by: Anna MacGillivray Project number: U.158 File reference: Genomics England/genomic medicine draft evaluation report 19.6.2019 URSUS CONSULTING LTD 57 Balfour Road London N5 2HD Tel. 07989 554 504 www.ursusconsulting.co.uk _________________________________________________________________________________________ URSUS CONSULTING GENOMICS ENGLAND AND SCIENCEWISE 2 Glossary of Acronyms ABI Association of British Insurers AI Artificial Intelligence APBI Association of British Pharmaceutical Industry BEIS (Department of) Business, Energy and Industrial Strategy BME Black and Minority Ethnic CMO Chief Medical Officer CSO (NHS) Chief Scientific Officer DA Devolved Administration DHSC Department of Health and Social Care FTE Full Time Equivalent GDPR General Data Protection Regulation GE Genomics England GG Generation Genome report GMS Genomic medicine service GMC General Medical Council NHS National Health Service OG Oversight Group REA Rapid Evidence Assessment SEG Socio economic group SGP Scottish Genomes Partnership SoS Secretary of State SSAC Scottish Science Advisory Committee SLT Senior Leadership Team UKRI UK Research and Innovation WGS Whole Genome Sequencing _________________________________________________________________________________________ URSUS CONSULTING GENOMICS ENGLAND AND SCIENCEWISE 3 EXECUTIVE SUMMARY Introduction This report of the independent evaluation of a public dialogue on Genomic Medicine: Time for a new social contract? has been prepared by URSUS Consulting Ltd on behalf of Genomics England (GE) and Sciencewise1. -
Development of Novel Strategies for Template-Based Protein Structure Prediction
Imperial College London Department of Life Sciences PhD Thesis Development of novel strategies for template-based protein structure prediction Stefans Mezulis supervised by Prof. Michael Sternberg Prof. William Knottenbelt September 2016 Abstract The most successful methods for predicting the structure of a protein from its sequence rely on identifying homologous sequences with a known struc- ture and building a model from these structures. A key component of these homology modelling pipelines is a model combination method, responsible for combining homologous structures into a coherent whole. Presented in this thesis is poing2, a model combination method using physics-, knowledge- and template-based constraints to assemble proteins us- ing information from known structures. By combining intrinsic bond length, angle and torsional constraints with long- and short-range information ex- tracted from template structures, poing2 assembles simplified protein models using molecular dynamics algorithms. Compared to the widely-used model combination tool MODELLER, poing2 is able to assemble models of ap- proximately equal quality. When supplied only with poor quality templates or templates that do not cover the majority of the query sequence, poing2 significantly outperforms MODELLER. Additionally presented in this work is PhyreStorm, a tool for quickly and accurately aligning the three-dimensional structure of a query protein with the Protein Data Bank (PDB). The PhyreStorm web server provides comprehensive, current and rapid structural comparisons to the protein data bank, providing researchers with another tool from which a range of biological insights may be drawn. By partitioning the PDB into clusters of similar structures and performing an initial alignment to the representatives of each cluster, PhyreStorm is able to quickly determine which structures should be excluded from the alignment. -
Algorithms for Computational Biology 8Th International Conference, Alcob 2021 Missoula, MT, USA, June 7–11, 2021 Proceedings
Lecture Notes in Bioinformatics 12715 Subseries of Lecture Notes in Computer Science Series Editors Sorin Istrail Brown University, Providence, RI, USA Pavel Pevzner University of California, San Diego, CA, USA Michael Waterman University of Southern California, Los Angeles, CA, USA Editorial Board Members Søren Brunak Technical University of Denmark, Kongens Lyngby, Denmark Mikhail S. Gelfand IITP, Research and Training Center on Bioinformatics, Moscow, Russia Thomas Lengauer Max Planck Institute for Informatics, Saarbrücken, Germany Satoru Miyano University of Tokyo, Tokyo, Japan Eugene Myers Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany Marie-France Sagot Université Lyon 1, Villeurbanne, France David Sankoff University of Ottawa, Ottawa, Canada Ron Shamir Tel Aviv University, Ramat Aviv, Tel Aviv, Israel Terry Speed Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia Martin Vingron Max Planck Institute for Molecular Genetics, Berlin, Germany W. Eric Wong University of Texas at Dallas, Richardson, TX, USA More information about this subseries at http://www.springer.com/series/5381 Carlos Martín-Vide • Miguel A. Vega-Rodríguez • Travis Wheeler (Eds.) Algorithms for Computational Biology 8th International Conference, AlCoB 2021 Missoula, MT, USA, June 7–11, 2021 Proceedings 123 Editors Carlos Martín-Vide Miguel A. Vega-Rodríguez Rovira i Virgili University University of Extremadura Tarragona, Spain Cáceres, Spain Travis Wheeler University of Montana Missoula, MT, USA ISSN 0302-9743 ISSN 1611-3349 (electronic) Lecture Notes in Bioinformatics ISBN 978-3-030-74431-1 ISBN 978-3-030-74432-8 (eBook) https://doi.org/10.1007/978-3-030-74432-8 LNCS Sublibrary: SL8 – Bioinformatics © Springer Nature Switzerland AG 2021 This work is subject to copyright.