Computational Methods for Cis-Regulatory Module Discovery A

Total Page:16

File Type:pdf, Size:1020Kb

Computational Methods for Cis-Regulatory Module Discovery A Computational Methods for Cis-Regulatory Module Discovery A thesis presented to the faculty of the Russ College of Engineering and Technology of Ohio University In partial fulfillment of the requirements for the degree Master of Science Xiaoyu Liang November 2010 © 2010 Xiaoyu Liang. All Rights Reserved. 2 This thesis titled Computational Methods for Cis-Regulatory Module Discovery by XIAOYU LIANG has been approved for the School of Electrical Engineering and Computer Science and the Russ College of Engineering and Technology by Lonnie R.Welch Professor of Electrical Engineering and Computer Science Dennis Irwin Dean, Russ College of Engineering and Technology 3 ABSTRACT LIANG, XIAOYU, M.S., November 2010, Computer Science Computational Methods for Cis-regulatory Module Discovery Director of Thesis: Lonnie R.Welch In a gene regulation network, the action of a transcription factor binding a short region in non-coding sequence is reported and believed as the key that triggers, or represses genes’ expression. Further analysis revealed that, in higher organisms, multiple transcription factors work together and bind multiple sites that are located nearby in genomic sequences, rather than working alone and binding a single anchor. These multiple binding sites in the non-coding region are called cis -regulatory modules. Identifying these cis - regulatory modules is important for modeling gene regulation network. In this thesis, two methods have been proposed for addressing the problem, and a widely accepted evaluation was applied for assessing the performance. Additionally, two practical case studies were completed and reported as the application of the proposed methods. Approved: _____________________________________________________________ Lonnie R.Welch Professor of Electrical Engineering and Computer Science 4 ACKNOWLEDGEMENTS I would like to express my sincere gratitude to my advisor, Dr. Lonnie R. Welch, for introducing me into the area of Bioinformatics, and for his guidance and encouragement for the present thesis and my research projects. I would like to extend my deep gratitude to Dr. Frank Drews, Dr. Sarah Wyatt, and Dr. Razvan Bunescu for all the help and advices for my research, and serving as my thesis committee members. Especially, thank Dr. Razvan Bunescu for teaching me machine learning knowledge and guiding me to develop the HAC algorithm that is proposed in this thesis. I would also like to thank Dr. Klaus Ecker for participating in my research projects, and for his valuable advice, discussion, and friendly help. I would also like to thank past and present members in Bioinformatics group, including Jens Litchenberg, Kyle Kurz, Rami Alouran, Lee Nau, Joshua Welch, Daniel Evans, Kaiyu Shen, Paul Burns, Lev Neimen, Zekai Huang, Eric Petri, Nathaniel George, and Josiah Seaman, for all your help and collaborations. Specially, thank to Jens Litchenberg for all advices, encouragements, and being a wonderful landlord. I would like to thank Dr. Wyatt and her lab again for providing data, and initial analysis of the case study of plant gravitropic signal pathway that is presented as one of the case studies in this thesis. 5 I would also like to thank Dr. Eric Grotewold and Dr. Alper Yilmaz for providing a priceless internship opportunity, and cooperating in the case study of comparison between rice and Arabidopsis thaliana , which is presented in this thesis. I have learned a lot in both theory and practical applications, and really enjoyed the experience working in their lab. Thank you to my parents deeply for always being support, for their love and understandings. I would also like to thank Stephane J. Litchenberg for correcting my grammatical errors and sharing friendship. 6 TABLE OF CONTENTS Page ABSTRACT ........................................................................................................................ 3 ACKNOWLEDGEMENTS ................................................................................................ 4 LIST OF TABLES ............................................................................................................ 10 LIST OF FIGURES .......................................................................................................... 12 LIST OF ABBREVIATIONS ........................................................................................... 14 CHAPTER 1: INTRODUCTION ..................................................................................... 15 1.1 Background ............................................................................................................. 15 1.2 Problem Statement .................................................................................................. 17 1.3 Overview of Thesis ................................................................................................. 19 CHAPTER 2: LITERATURE REVIEW .......................................................................... 20 2.1 With Prior Knowledge of TFBSs............................................................................ 21 2.2 Without Prior Knowledge of TFBSs ...................................................................... 25 CHAPTER 3: PROBLEM DEFINITION......................................................................... 28 3.1 Introduction ............................................................................................................. 28 3.2 Terminologies ......................................................................................................... 28 CHAPTER 4: WORDSEEKER ........................................................................................ 35 4.1 WordSeeker Design ................................................................................................ 35 7 4.2 Integration with WordSeeker .................................................................................. 38 CHAPTER 5: ALGORITHMIC APPROACHES FOR MODULE DISCOVERY ......... 40 5.1 Enumerative Module Discovery Method ................................................................ 41 5.1.1 Motivation ........................................................................................................ 41 5.1.2 Algorithm ......................................................................................................... 43 5.1.3 Complexity Analysis ........................................................................................ 50 5.2 Hierachical Agglomerative Clustering (HAC) Module Discovery Method ........... 52 5.2.1 Motivation ........................................................................................................ 52 5.2.2 Algorithm ......................................................................................................... 52 5.2.3 Complexity Analysis ........................................................................................ 58 CHAPTER 6: EVALUATION ......................................................................................... 59 6.1 Benchmark Datasets ............................................................................................... 59 6.1.1 TRANSCompel ................................................................................................ 60 6.1.2 Muscle Dataset ................................................................................................. 61 6.1.3 Liver Dataset .................................................................................................... 62 6.2 Evaluation of Scoring Functions............................................................................. 63 6.2.1 AP1-NFAT ....................................................................................................... 64 6.2.2 AP1-Ets ............................................................................................................ 70 6.2.3 AP1-NFkappaB ................................................................................................ 75 8 6.2.4 CEBP-NFkappaB ............................................................................................. 79 6.2.5 Ebox-Ets ........................................................................................................... 82 6.2.6 Ets-AML .......................................................................................................... 85 6.2.7 IRF-NFkappaB ................................................................................................. 91 6.2.8 NFkappaB-HMGIY ......................................................................................... 97 6.2.9 PU1-IRF ........................................................................................................... 97 6.2.10 Sp1-Ets ......................................................................................................... 102 6.2.11 Discussion .................................................................................................... 107 6.3 Evaluation of Prediction Performance .................................................................. 108 6.3.1 Statistical Values ............................................................................................ 108 6.3.2 Statistical Formulas ........................................................................................ 110 6.3.3 Results and Discussion .................................................................................. 111 CHAPTER 7: CASE STUDY......................................................................................... 121 7.1 Plant Gravitropic Signal
Recommended publications
  • ACCEPTED PAPERS – ABSTRACTS (As of May 5, 2006) Comparative
    ACCEPTED PAPERS – ABSTRACTS (as of May 5, 2006) Comparative Genomics Hairpins in a haystack: recognizing microrna precursors in comparative genomics data Author(s): Jana Hertel, Peter F. Stadler Recently, genome wide surveys for non-coding RNAs have provided evidence for tens of thousands of previously undescribed evolutionary conserved RNAs with distinctive secondary structures. The annotation of these putative ncRNAs, however, remains a difficult problem. Here we describe an SVM-based approach that, in conjunction with a non-stringent filter for consensus secondary structures, is capable of efficiently recognizing microRNA precursors in multiple sequence alignments. The software was applied to recent genome-wide RNAz surveys of mammals, urochordates, and nematodes. Keywords: miRNA, support vector machine, non-coding RNA Comparative Genomics Comparative genomics reveals unusually long motifs in mammalian genomes Author(s): Neil Jones, Pavel Pevzner Motivation: The recent discovery of the first small modulatory RNA (smRNA) presents the challenge of finding other molecules of similar length and conservation level. Unlike short interfering RNA (siRNA) and micro-RNA (miRNA), effective computational and experimental screening methods are not currently known for this species of RNA molecule, and the discovery of the one known example was partly fortuitous because it happened to be complementary to a well-studied DNA binding motif (the Neuron Restrictive Silencer Element). Results: The existing comparative genomics approaches (e.g., phylogenetic footprinting) rely on alignments of orthologous regions across multiple genomes. This approach, while extremely valuable, is not suitable for finding motifs with highly diverged ``non-alignable'' flanking regions. Here we show that several unusually long and well conserved motifs can be discovered de novo through a comparative genomics approach that does not require an alignment of orthologous upstream regions.
    [Show full text]
  • Daniel Aalberts Scott Aa
    PLOS Computational Biology would like to thank all those who reviewed on behalf of the journal in 2015: Daniel Aalberts Jeff Alstott Benjamin Audit Scott Aaronson Christian Althaus Charles Auffray Henry Abarbanel Benjamin Althouse Jean-Christophe Augustin James Abbas Russ Altman Robert Austin Craig Abbey Eduardo Altmann Bruno Averbeck Hermann Aberle Philipp Altrock Ferhat Ay Robert Abramovitch Vikram Alva Nihat Ay Josep Abril Francisco Alvarez-Leefmans Francisco Azuaje Luigi Acerbi Rommie Amaro Marc Baaden Orlando Acevedo Ettore Ambrosini M. Madan Babu Christoph Adami Bagrat Amirikian Mohan Babu Frederick Adler Uri Amit Marco Bacci Boris Adryan Alexander Anderson Stephen Baccus Tinri Aegerter-Wilmsen Noemi Andor Omar Bagasra Vera Afreixo Isabelle Andre Marc Baguelin Ashutosh Agarwal R. David Andrew Timothy Bailey Ira Agrawal Steven Andrews Wyeth Bair Jacobo Aguirre Ioan Andricioaei Chris Bakal Alaa Ahmed Ioannis Androulakis Joseph Bak-Coleman Hasan Ahmed Iris Antes Adam Baker Natalie Ahn Maciek Antoniewicz Douglas Bakkum Thomas Akam Haroon Anwar Gabor Balazsi Ilya Akberdin Stefano Anzellotti Nilesh Banavali Eyal Akiva Miguel Aon Rahul Banerjee Sahar Akram Lucy Aplin Edward Banigan Tomas Alarcon Kevin Aquino Martin Banks Larissa Albantakis Leonardo Arbiza Mukul Bansal Reka Albert Murat Arcak Shweta Bansal Martí Aldea Gil Ariel Wolfgang Banzhaf Bree Aldridge Nimalan Arinaminpathy Lei Bao Helen Alexander Jeffrey Arle Gyorgy Barabas Alexander Alexeev Alain Arneodo Omri Barak Leonidas Alexopoulos Markus Arnoldini Matteo Barberis Emil Alexov
    [Show full text]
  • Dear Delegates,History of Productive Scientific Discussions of New Challenging Ideas and Participants Contributing from a Wide Range of Interdisciplinary fields
    3rd IS CB S t u d ent Co u ncil S ymp os ium Welcome To The 3rd ISCB Student Council Symposium! Welcome to the Student Council Symposium 3 (SCS3) in Vienna. The ISCB Student Council's mis- sion is to develop the next generation of computa- tional biologists. We would like to thank and ac- knowledge our sponsors and the ISCB organisers for their crucial support. The SCS3 provides an ex- citing environment for active scientific discussions and the opportunity to learn vital soft skills for a successful scientific career. In addition, the SCS3 is the biggest international event targeted to students in the field of Computational Biology. We would like to thank our hosts and participants for making this event educative and fun at the same time. Student Council meetings have had a rich Dear Delegates,history of productive scientific discussions of new challenging ideas and participants contributing from a wide range of interdisciplinary fields. Such meet- We are very happy to welcomeings have you proved all touseful the in ISCBproviding Student students Council and postdocs Symposium innovative inputsin Vienna. and an Afterincreased the network suc- cessful symposiums at ECCBof potential 2005 collaborators. in Madrid and at ISMB 2006 in Fortaleza we are determined to con- tinue our efforts to provide an event for students and young researchers in the Computational Biology community. Like in previousWe ar yearse extremely our excitedintention to have is toyou crhereatee and an the opportunity vibrant city of Vforienna students welcomes to you meet to our their SCS3 event. peers from all over the world for exchange of ideas and networking.
    [Show full text]
  • An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement in Accuracy
    The University of Southern Mississippi The Aquila Digital Community Faculty Publications 9-7-2016 An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement In Accuracy Yuxiang Jiang Indiana University TFollowal Ronnen this and Or onadditional works at: https://aquila.usm.edu/fac_pubs Buck P arInstitutet of the forGenomics Research Commons On Agin Wyatt T. Clark RecommendedYale University Citation AsmaJiang, YR.., OrBankapuron, T. R., Clark, W. T., Bankapur, A. R., D'Andrea, D., Lepore, R., Funk, C. S., Kahanda, I., Verspoor, K. M., Ben-Hur, A., Koo, D. E., Penfold-Brown, D., Shasha, D., Youngs, N., Bonneau, R., Lin, A., Sahraeian, S. Miami University M., Martelli, P. L., Profiti, G., Casadio, R., Cao, R., Zhong, Z., Cheng, J., Altenhoff, A., Skunca, N., Dessimoz, DanielC., Dogan, D'Andr T., Hakala,ea K., Kaewphan, S., Mehryar, F., Salakoski, T., Ginter, F., Fang, H., Smithers, B., Oates, M., UnivGough,ersity J., ofTör Romeönen, P., Koskinen, P., Holm, L., Chen, C., Hsu, W., Bryson, K., Cozzetto, D., Minneci, F., Jones, D. T., Chapan, S., BKC, D., Khan, I. K., Kihara, D., Ofer, D., Rappoport, N., Stern, A., Cibrian-Uhalte, E., Denny, P., Foulger, R. E., Hieta, R., Legge, D., Lovering, R. C., Magrane, M., Melidoni, A. N., Mutowo-Meullenet, P., SeePichler next, K., page Shypitsyna, for additional A., Li, B.,authors Zakeri, P., ElShal, S., Tranchevent, L., Das, S., Dawson, N. L., Lee, D., Lees, J. G., Stilltoe, I., Bhat, P., Nepusz, T., Romero, A. E., Sasidharan, R., Yang, H., Paccanaro, A., Gillis, J., Sedeño- Cortés, A. E., Pavlidis, P., Feng, S., Cejuela, J.
    [Show full text]
  • Studying the Regulatory Landscape of Flowering Plants
    Studying the Regulatory Landscape of Flowering Plants Jan Van de Velde Promoter: Prof. Dr. Klaas Vandepoele Co-Promoter: Prof. Dr. Jan Fostier Ghent University Faculty of Sciences Department of Plant Biotechnology and Bioinformatics VIB Department of Plant Systems Biology Comparative and Integrative Genomics Research funded by a PhD grant of the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT Vlaanderen). Dissertation submitted in fulfilment of the requirements for the degree of Doctor in Sciences:Bioinformatics. Academic year: 2016-2017 Examination Commitee Prof. Dr. Geert De Jaeger (chair) Faculty of Sciences, Department of Plant Biotechnology and Bioinformatics, Ghent University Prof. Dr. Klaas Vandepoele (promoter) Faculty of Sciences, Department of Plant Biotechnology and Bioinformatics, Ghent University Prof. Dr. Jan Fostier (co-promoter) Faculty of Engineering and Architecture, Department of Information Technology (INTEC), Ghent University - iMinds Prof. Dr. Kerstin Kaufmann Institute for Biochemistry and Biology, Potsdam University Prof. Dr. Pieter de Bleser Inflammation Research Center, Flanders Institute of Biotechnology (VIB) and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium Dr. Vanessa Vermeirssen Faculty of Sciences, Department of Plant Biotechnology and Bioinformatics, Ghent University Dr. Stefanie De Bodt Crop Science Division, Bayer CropScience SA-NV, Functional Biology Dr. Inge De Clercq Department of Animal, Plant and Soil Science, ARC Centre of Excellence in Plant Energy Biology, La Trobe University and Faculty of Sciences, Department of Plant Biotechnology and Bioinformatics, Ghent University iii Thank You! Throughout this PhD I have received a lot of support, therefore there are a number of people I would like to thank. First of all, I would like to thank Klaas Vandepoele, for his support and guidance.
    [Show full text]
  • Reconstruction of Gene Regulatory Network from Expression Profile of Plasma RNA Data of Colorectal Cancer Patients Using Soft Computing Techniques
    Reconstruction of Gene Regulatory Network from Expression Profile of Plasma RNA Data of Colorectal Cancer Patients using Soft Computing Techniques Thesis Submitted by VINEETHA S In partial fulfillment of the requirements for the award of the degree of DOCTOR OF PHILOSOPHY UNDER THE FACULY OF TECHNOLOGY DEPARTMENT OF COMPUTER SCIENCE COCHIN UNIVERSITY OF SCIENCE AND TECHNOLOGY KOCHI-682 022 INDIA October 2012 i ii Certificate This is to certify that the thesis entitled “Reconstruction of Gene Regulatory Network from Expression Profile of Plasma RNA Data of Colorectal Cancer Patients using Soft Computing Techniques” is a bonafide record of the research work carried out by Ms. Vineetha S in the Department of Computer Science, Cochin University of Science and Technology, Kochi-682022, under my supervision and guidance. Kochi-682022 Dr. Sumam Mary Idicula October, 2012 Supervising Guide, Professor, Department of Computer Science Cochin University of Science and Technology, Kochi-682022, Kerala iii iv DECLARATION I hereby declare that the work presented in this thesis entitled “Reconstruction of Gene Regulatory Network from Expression Profile of Plasma RNA Data of Colorectal Cancer Patients using Soft Computing Techniques” is based on the original research work carried out by me in the Department of Computer Science, Cochin University of Science and Technology, Kochi-682022, under the supervision and guidance of Dr. Sumam Mary Idicula, Professor, Department of Computer Science , Cochin University of Science and Technology , Kochi-682022.The results presented in this thesis or parts of it have not been presented for the award of any other degree. Kochi-682022 Vineetha S October 2012 Research Scholar v vi vii viii The work on this thesis would not have been possible without the encouragement and support of many people who in one way or another have contributed in the completion of this study.
    [Show full text]
  • Computational Study of Transcriptional Regulation - from Sequence to Expression
    Computational Study of Transcriptional Regulation - From Sequence To Expression Shan Zhong CMU-CB-13-101 May 2013 School of Computer Science Carnegie Mellon University Pittsburgh, PA 15213 Thesis Committee: Ziv Bar-Joseph, Chair Roni Rosenfeld Seyoung Kim Takis Benos (University of Pittsburgh) Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Copyright c 2013 Shan Zhong Keywords: Motif finding, Transcriptional regulatory network, p53, Protein binding microar- ray, Tissue specificity, EIN3, Ethylene response To my parents, my wife, and my soon-to-be-born son. iv Abstract Transcription is the process during which RNA molecules are synthesized based on the DNAs in cells. Transcription leads to gene expression, and it is the first step in the flow of genetic information from DNA to proteins that carry out bio- logical functions. Transcription is tightly regulated both spatially and temporally at multiple levels, so that the amount of mRNAs produced for different genes is controlled across different kinds of cells and tissues, as well as in different devel- opmental stages and in response to different environmental stimulus. In eukaryotes, transcription is a complicated process and its regulation involves both cis-regulatory elements and trans-acting factors. By studying spatiotemporally what genes are reg- ulated by which cis-elements and trans-factors, we can get a better understanding of how we develop, how we react to environmental signals, and the mechanisms behind diseases like cancer that, at least in part, result from failures in proper transcriptional regulation. In this thesis, we present a suite of computational methods and analyses that, combined, provide a solution to problems related to the identification of DNA bind- ing motifs, linking these motifs to the TFs that bind them and the genes that they con- trol, and integrating these motifs and interactions with time series expression data to model dynamic regulatory networks.
    [Show full text]
  • Friday (August 4) Intelligent Systems for Molecular Biology
    and 2nd Annual AB3C Conference: X-Meeting fortaleza, brazil - auGust 6-10, 2006 friday (auGust 4) Intelligent Systems for Molecular Biology Room A Room B1 Room E1 (2nd Floor) 7:00 a.m. Shuttles depart Hotels to Convention Center 7:30 a.m. - 6:00 p.m. Registration - Hall G 3Dsig Alternative Splicing BOSC 9:00 a.m. - 10:30 a.m. Satellite Meeting SIG SIG 10:30 a.m. - 11:00 a.m. Coffee Break - Satellite & SIG meetings (available outside meeting rooms) 3Dsig Alternative Splicing BOSC 11:00 a.m - 12:00 p.m. Satellite Meeting SIG SIG 12:00 p.m. - 1:00 p.m. Lunch - Satellite and SIG meetings (Hall F) 3Dsig Alternative Splicing BOSC 1:00 p.m. - 3:30 p.m. Satellite Meeting SIG SIG 3:30 p.m. - 4:00 p.m. Coffee Break - Satellite & SIG meetings (available outside meeting rooms) 3Dsig Alternative Splicing BOSC 4:00 p.m. - 6:30 p.m. Satellite Meeting SIG SIG 6:30 p.m. Shuttles depart Convention Center to Hotels 1 and 2nd Annual AB3C Conference: X-Meeting fortaleza, brazil - auGust 6-10, 2006 saturday (auGust 5) Intelligent Systems for Molecular Biology Room A Room B1 Room B2 Room E1 (2nd Floor) 7:00 a.m. Shuttles depart Hotels to Convention Center 7:30 a.m. - 6:00 p.m. Registration - Hall G Joint BioLINK & 3Dsig Alternative Splicing Bio-ontologies BOSC 9:00 a.m. - 10:30 a.m. Satellite Meeting SIG SIG SIG 10:30 a.m. - 11:00 a.m. Coffee Break - Satellite & SIG meetings (available outside meeting rooms) Joint BioLINK & 3Dsig Alternative Splicing Bio-ontologies BOSC 11:00 a.m - 12:00 p.m.
    [Show full text]
  • Exploiting Biological Pathways to Infer Temporal Gene Interaction
    Exploiting Biological Pathways to Infer Temporal Gene Interaction Models by Corey Ann Kemper Submitted to the Department of Electrical Engineering and Computer Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Computer Science and Engineering at the MASSACHUSETTS INSTITUTE OF TECHNOLOGY August 2006 c Massachusetts Institute of Technology 2006. All rights reserved. Author............................................... ............... Department of Electrical Engineering and Computer Science August, 2006 Certified by........................................... ............... W. Eric L. Grimson Bernard Gordon Professor of Medical Engineering Thesis Supervisor Certified by........................................... ............... John Fisher Principal Research Scientist Thesis Supervisor Accepted by........................................... .............. Arthur C. Smith Chairman, Department Committee on Graduate Students Exploiting Biological Pathways to Infer Temporal Gene Interaction Models by Corey Ann Kemper Submitted to the Department of Electrical Engineering and Computer Science on August, 2006, in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Computer Science and Engineering Abstract An important goal in genomic research is the reconstruction of the complete picture of temporal interactions among all genes, but this inference problem is not tractable because of the large number of genes, the small number of experimental observations for each gene, and the
    [Show full text]
  • CV Burkhard Rost TUM Technical University of Munich Affiliation: Columbia University
    Burkhard Rost CV BURKHARD ROST TUM Informatics/Bioinformatics i12 Boltzmannstrasse 3 (Rm 01.09.052) 85748 Garching/München, Germany & Dept. Biochemistry & Molecular Biophysics Columbia University, New York, USA Email [email protected] Tel +49-89-289-17-811 Web www.rostlab.org Fax +49-89-289-19-414 Photo: © Eckert & Heddergott, TUM Document: CV Burkhard Rost TUM Technical University of Munich Affiliation: Columbia University Highlights: • 208 invited talks in 37 countries (incl. TedX) • 272 publications (212 peer-review, 183 first/last author) • 2019/03: >38,500 citations, h-index=91 (Google) • PredictProtein 1st Internet server in mol. biol. (since 1992) • 8 years ISCB President (International Society for Computational Biology) • 207 trained (27% female, 55% foreigners from 37 nations on 6 continents) • co-published with over 984 scientists Brief narrative: Burkhard Rost obtained his doctoral degree (Dr. rer. nat.) from the Univ. of Heidelberg (Germany) in the field of theoretical physics. He began his research working on the thermo-dynamical properties of spin glasses and brain-like artificial neural networks. A short project on peace/arms control research sketched a simple, non-intrusive sensor networks to monitor aircraft (1988-1990). He entered the field of molecular biology at the European Molecular Biology Laboratory (EMBL, Heidelberg, Germany, 1990-1995), spent a year at the European Bioinformatics Institute (EBI, Hinxton, Cambridgshire, England, 1995), returned to the EMBL (1996-1998), joined the company LION Biosciences for a brief interim (1998), became faculty in the Medical School of Columbia University in 1998, and joined the TUM Munich to become an Alexander von Humboldt professor in 2009.
    [Show full text]
  • ©Copyright 2021 Timothy R. Bergquist
    ©Copyright 2021 Timothy R. Bergquist Ensuring patient privacy and accuracy of analytical methods to support evidence-based healthcare Timothy R. Bergquist A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2021 Reading Committee: Sean D. Mooney, Chair Justin Guinney David Crosslin Brian Shirts Program Authorized to Offer Degree: Department of Biomedical Informatics and Medical Education University of Washington Abstract Ensuring patient privacy and accuracy of analytical methods to support evidence-based healthcare Timothy R. Bergquist Chair of the Supervisory Committee: Professor Sean D. Mooney Department of Biomedical Informatics and Medical Education Over the past two decades, healthcare providers substantially increased their use of elec- tronic health record (EHR) systems. EHRs are primed to become the core of the data driven healthcare system, with the potential to serve as a platform for population health an- alytics, predictive model development and implementation, and coordination with patients to manage their health information. However, research with EHRs introduces the risk of exposing patient records and business practices to nefarious actors. Creating infrastructure to deliver predictive methods to clinical records while protecting patient privacy is key to building a reliable healthcare analytics platform. In addition, the quality of data from these systems is not fully validated for all use cases, such as assessing population health. Val- idating the utility of EHRs for use as a population health platform is necessary to fully realize the vision of the data driven health system. Patient involvement in their health is essential to maximize positive patient outcomes. While many vectors exist for patients to access their health information, they are still limited in their ability to contribute to their health data.
    [Show full text]
  • Ismb 2016 Proceedings Papers Committee
    Bioinformatics, 32, 2016, i3–i7 doi: 10.1093/bioinformatics/btw296 ISMB 2016 PROCEEDINGS PAPERS COMMITTEE PROCEEDINGS PAPERS THEME CHAIRS Disease Models & Epidemiology Data Trey Ideker, University of California, San Diego, United States Alex Bateman, European Bioinformatics Institute (EMBL-EBI), Maricel Kann, University of Maryland, Baltimore County, United Hinxton, United Kingdom States Bonnie Berger, Massachusetts Institute of Technology, Cambridge, United States Evolution & Comparative Genomics/Proteomics Diseases Bernard Moret, The Swiss Federal Institute of Technology, Yana Bromberg, Rutgers University, New Brunswick, United States Lausanne, Switzerland Yves Moreau, KU Leuven, Belgium Matthieu Blanchette, McGill University, Montreal, Canada Genes Gene Regulation Russell Schwartz, Carnegie Mellon University, Pittsburgh, United Uwe Ohler, Max Delbruck Center for Molecular Medicine, Berlin, States Germany Jean-Philippe Vert, MINES ParisTech and Institut Curie, Paris, Cenk Sahinalp, Indiana University, Bloomington, United States France Gene/Protein Sequence Analysis Proteins Siu Ming Yiu, The University of Hong Kong Ioannis Xenarios, University of Lausanne, Switzerland Knut Reinert, Free University Berlin, Germany David Jones, University College London, United Kingdom Systems Population Genomics Niko Beerenwinkel, ETH Zurich, Basel, Switzerland Jennifer Listgarten, Microsoft Research, Cambridge, United States Donna Slonim, Tufts University, Medford, United States Oliver Stegle, The European Bioinformatics Institute (EMBL-EBI), Hinxton,
    [Show full text]