DOCSLIB.ORG

Development and Application of Ligand-Based Cheminformatics Tools for Drug Discovery from Natural Products

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Development and Application of Ligand-Based Cheminformatics Tools for Drug Discovery from Natural Products Development and application of ligand-based cheminformatics tools for drug discovery from natural products Entwicklung und Anwendung von ligandenbasierten Cheminformatik-Programmen für die Identifizierung von Arzneimitteln aus Naturstoffen INAUGURALDISSERTATION zur Erlangung des Doktorgrades der Fakultät für Chemie und Pharmazie der Albert-Ludwigs-Universität Freiburg im Breisgau vorgelegt von Kiran Kumar Telukunta aus Hyderabad, Indien Juli 2018 Dekan: Prof. Dr. Manfred Jung Universität Freiburg Institut für Pharmazeutische Wissenschaften Chemische Epigenetik Albertstraße 25 79104 Freiburg Vorsitzender: Prof. Dr. Stefan Weber des Promotionsausschusses Universität Freiburg Institut für Physikalische Chemie Physikalishe Chemie Albertstraße 21 79104 Freiburg Referent: Prof. Dr. Stefan Günther Universität Freiburg Institut für Pharmazeutische Wissenschaften Pharmazeutische Bioinformatik Hermann-Herder-Straße 9 79104 Freiburg Korreferent: Prof. Dr. Rolf Backofen Universität Freiburg Institut für Informatik Lehrstuhl für Bioinformatik Georges-Köhler-Allee 106 79110 Freiburg Drittprüfer: Prof. Dr. Andreas Bechthold Universität Freiburg Institut für Pharmazeutische Wissenschaften Pharmazeutische Biologie und Biotechnologie Stefan-Meier-Straße 19 79104 Freiburg Prüfungsdatum: 30 Aug 2018 Eidesstattliche Erklärung Hiermit erkläre ich, dass ich diese Arbeit allein und ausschließlich unter Nutzung der direkt oder sinngemäß gekennzeichneten Zitate geschrieben habe. Weiterhin versichere ich, dass diese Arbeit in keinem anderen Prüfungsverfahren eingereicht wurde. Kiran Kumar Telukunta Juli 2018 Acknowledgements “Learning gives creativity; Creativity leads to thinking; Thinking provides knowledge; Knowledge makes you great." -A. P.J. Abdul Kalam • Primarily I thank athletic Prof. Dr. Stefan Günther for giving me the opportunity to be part of Pharmaceutical Bioinformatics group, where I enjoyed my journey of knowledge and challenges of science expedition. I am happy to see his journey from Junior Professor to a Professor which gives me enormous motivation both personally and professionally. His diverse group of knowledge and peer PhDs from various countries making it a unique international research group provides a set platform with great exposure. I am fortunate to have Prof. Dr. Rolf Backofen again as supervisor to my Ph.D. and my special thanks to him. My gratitude to Prof. Dr. Andreas Bechthold for accepting to be my third supervisor. • I sincerely thank my funding institutions German National Research Foundation (DFG) and University of Freiburg. • One of the high motivation for me pursuing Ph.D. and completing it is the philosophy of IndiaYouth.info which I have quoted in my master thesis, and I am blissful that this envision still sought and it evolved in me in every Planck length (lp) of the moment. This philosophy gave me the opportunity to thank Rama Rao Madarapu who joined me in this philosophy and gradually became part of my life. His substantial support is an essential asset during this period. viii • I’m happy that Dr. Stephan Flemming and Dr. Xavier Lucas born in different countries because now I can express this easily that if somebody asks me if I were to born in Germany or Spain then probably I would have been like these guys respectively. They were everything to me in my new country of living. Both of them were always accessible and available for my ideas, queries and all topics of discussion. More importantly, several exciting activities with these guys will always be great memories in my life. • Dr. Björn Grünning and Dr. Fidele Ntie-Kang were great inspiring colleagues during my Ph.D. Their maximum utilization of their resources in contributing to scientific progress is admirable. • It was enormous pleasant feeling working and contributing to science along with Dr. Kersten Döring, Dr. Dennis Klementz, and Paul Zierep. I had a lovely environment working with Dr. Anika Erxleben, Pankaj Mishra, Dr. Gwang-Jin Kim, Mehrosh Pervaiz, Ammar Qaseem, Jianyu Li, Stefan Bleher, Dr. Martin Gotthardt, Dr. Nan Liu, Daniel Eckhardt, Dr. Maria Hörnke, and Lars Rösch. • I thank Moritz Konrad, Laura van Hazendonk, and Lea Purschke for being part of my work team during my stay at Pharmaceutical Bioinformatics. • My respect to the source of my life is my parents for their love and support. I gratefully appreciate and thank the unconditional support of my sister, brother-in-law, and especially my Aunt and Uncle during the journey of my Ph.D. Meinen großen Respekt und meine Liebe zu meiner deutschen Mutter Gudrun Lorenz und Familie, die mir ein besonderes Familiengefühl in Deutschland vermittelt hat. • In the end but the extraordinarily special person in my life is my life partner Sheetal Arya Telukunta who gave me the opportunity of going through all my emotions during this period gives me immense pleasure in my joyride, and I am remarkably thankful to her for all sensations she has given to me. • I thank my second home Germany for all its support during my Masters and Doctorate. Abstract In the drug-discovery identification of small molecules that selectively bind to a biological target from virtually infinite chemical space is a time-consuming crucial step among many other critical steps in drug development. Identified molecules need to possess adequate residence times of drug-target complexes to modulate the function of the target protein and must affect the desirable phenotype. Furthermore, examination of the pharmacological activity of compounds in in vivo studies is required which are characterized by pharmacoki- netic and pharmacodynamic properties. Finally, the efficacy of the drug has to be validated in human. The huge number of natural products being approved drugs indicates the importance of natural compounds for drug discovery. Genome-mining tools can be applied to identify a substantial number of novel natural products and ligand- or structure-based virtual screen- ing methods will further increase the pace of therapeutic compound discovery. The present doctoral thesis focuses on developing cheminformatic tools which aid basic research for lead identification in drug development. The following applications were co- developed within the scope of this work: Tools evaluating existing literature by applying text-mining in natural language processing are becoming an essential part of identifying compound-protein, drug-drug, and protein- protein interactions along with their associations to diseases in literature. PubMedPortable is a framework developed for accessing large-scale biomolecule associated data and bridges the gap between natural language processing components and relation extraction methods by providing a local queryable and searchable instance of the literature. NANPDB annotates thousands of compounds from the Northern African region; Strep- x tomeDB is an updated database of molecules produced by actinobacteria. Both developed libraries contribute significantly to the biologically relevant natural chemical space. Fur- thermore, provided web services allow for the retrieval of information about a therapeutic application, physicochemical properties, and synthesis routes. Structural elucidation of biosynthetic substances is a hurdle. The developed web tool SeMPI provides a pipeline to identify encoding gene clusters from genomic data and predicts the basic structure of related natural products. DVS offers an algorithm that serves to narrow down the chemical space that has to be screened to identify putative drugs. FragPred provides a solution in another direction by predicting the activity of compounds based on the knowledge of contained active substruc- tures. The cheminformatic tools presented in the thesis are useful for creating hypotheses for the discovery of novel drugs to certain diseases. A case study, diabetes mellitus, illustrates these tools and their operation. Starting with finding literature on diabetes mellitus and the identi- fication of existing drugs for treatment, proposes alternative compounds from the presented natural databases. Finally, for the alternative compounds, putative targets are predicted. The manifested drug-discovery cheminformatic tools demonstrate the importance of in silico methods in modern drug discovery. Zusammenfassung Die Identifizierung kleiner Moleküle aus dem nahezu unendlichen chemischen Raum, die selektiv an ein biologisches Zielprotein binden, ist neben vielen anderen kritischen Schritten in der Arzneimittelentwicklung ein zeitaufwändiger Prozess. Identifizierte Moleküle müssen über ausreichende Verweilzeiten am Wirkstoff-Zielkomplex verfügen, um auf die Funktion des Zielproteins einzuwirken und den gewünschten Phänotyp zu beeinflussen. Darüber hinaus charakterisieren pharmakokinetische und pharmakodynamische Eigenschaften die pharmakologische Aktivität von Molekülen, die in in vivo Studien weiter untersucht werden muss. Schließlich muss die Wirksamkeit des Medikaments im Menschen validiert werden. Die große Zahl der zugelassenen Naturstoffe zeigt deren Bedeutung für die Arzneimit- telforschung. Genome-mining kann eingesetzt werden, um eine Vielzahl neuartiger Natur- produkte zu identifizieren. Liganden- oder strukturbasierte virtuelle screening-Methoden unterstützen die Entdeckung neuer therapeutischer Wirkstoffe. Die vorliegende Dissertation beschäftigt sich mit der Entwicklung cheminformatischer Werkzeuge, mit deren Hilfe die Grundlagenforschung zur Identifizierung von Leitstrukturen unterstützt werden kann. Die folgenden Anwendungen wurden im Rahmen dieser Arbeit
Load more

Recommended publications
  • Proquest Dissertations
    Automated learning of protein involvement in pathogenesis using integrated queries Eithon Cadag A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2009 Program Authorized to Offer Degree: Department of Medical Education and Biomedical Informatics UMI Number: 3394276 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. UMI Dissertation Publishing UMI 3394276 Copyright 2010 by ProQuest LLC. All rights reserved. This edition of the work is protected against unauthorized copying under Title 17, United States Code. uest ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 University of Washington Graduate School This is to certify that I have examined this copy of a doctoral dissertation by Eithon Cadag and have found that it is complete and satisfactory in all respects, and that any and all revisions required by the final examining committee have been made. Chair of the Supervisory Committee: Reading Committee: (SjLt KJ. £U*t~ Peter Tgffczy-Hornoch In presenting this dissertation in partial fulfillment of the requirements for the doctoral degree at the University of Washington, I agree that the Library shall make its copies freely available for inspection. I further agree that extensive copying of this dissertation is allowable only for scholarly purposes, consistent with "fair use" as prescribed in the U.S.
    [Show full text]
  • Molecular Biology for Computer Scientists
    CHAPTER 1 Molecular Biology for Computer Scientists Lawrence Hunter “Computers are to biology what mathematics is to physics.” — Harold Morowitz One of the major challenges for computer scientists who wish to work in the domain of molecular biology is becoming conversant with the daunting intri- cacies of existing biological knowledge and its extensive technical vocabu- lary. Questions about the origin, function, and structure of living systems have been pursued by nearly all cultures throughout history, and the work of the last two generations has been particularly fruitful. The knowledge of liv- ing systems resulting from this research is far too detailed and complex for any one human to comprehend. An entire scientific career can be based in the study of a single biomolecule. Nevertheless, in the following pages, I attempt to provide enough background for a computer scientist to understand much of the biology discussed in this book. This chapter provides the briefest of overviews; I can only begin to convey the depth, variety, complexity and stunning beauty of the universe of living things. Much of what follows is not about molecular biology per se. In order to 2ARTIFICIAL INTELLIGENCE & MOLECULAR BIOLOGY explain what the molecules are doing, it is often necessary to use concepts involving, for example, cells, embryological development, or evolution. Bi- ology is frustratingly holistic. Events at one level can effect and be affected by events at very different levels of scale or time. Digesting a survey of the basic background material is a prerequisite for understanding the significance of the molecular biology that is described elsewhere in the book.
    [Show full text]
  • Ontology-Based Methods for Analyzing Life Science Data
    Habilitation a` Diriger des Recherches pr´esent´ee par Olivier Dameron Ontology-based methods for analyzing life science data Soutenue publiquement le 11 janvier 2016 devant le jury compos´ede Anita Burgun Professeur, Universit´eRen´eDescartes Paris Examinatrice Marie-Dominique Devignes Charg´eede recherches CNRS, LORIA Nancy Examinatrice Michel Dumontier Associate professor, Stanford University USA Rapporteur Christine Froidevaux Professeur, Universit´eParis Sud Rapporteure Fabien Gandon Directeur de recherches, Inria Sophia-Antipolis Rapporteur Anne Siegel Directrice de recherches CNRS, IRISA Rennes Examinatrice Alexandre Termier Professeur, Universit´ede Rennes 1 Examinateur 2 Contents 1 Introduction 9 1.1 Context ......................................... 10 1.2 Challenges . 11 1.3 Summary of the contributions . 14 1.4 Organization of the manuscript . 18 2 Reasoning based on hierarchies 21 2.1 Principle......................................... 21 2.1.1 RDF for describing data . 21 2.1.2 RDFS for describing types . 24 2.1.3 RDFS entailments . 26 2.1.4 Typical uses of RDFS entailments in life science . 26 2.1.5 Synthesis . 30 2.2 Case study: integrating diseases and pathways . 31 2.2.1 Context . 31 2.2.2 Objective . 32 2.2.3 Linking pathways and diseases using GO, KO and SNOMED-CT . 32 2.2.4 Querying associated diseases and pathways . 33 2.3 Methodology: Web services composition . 39 2.3.1 Context . 39 2.3.2 Objective . 40 2.3.3 Semantic compatibility of services parameters . 40 2.3.4 Algorithm for pairing services parameters . 40 2.4 Application: ontology-based query expansion with GO2PUB . 43 2.4.1 Context . 43 2.4.2 Objective .
    [Show full text]
  • The International Society for Computational Biology 10Th Anniversary Lawrence Hunter, Russ B
    Message from ISCB The International Society for Computational Biology 10th Anniversary Lawrence Hunter, Russ B. Altman, Philip E. Bourne* Introduction training programs in bioinformatics or significant part of the original computational biology. By 1996, motivation for founding the Society PLoS Computational Biology is the however, high throughput molecular was to provide a stable financial home official journal of the International biology and the attendant need for for the ISMB conference. The first few Society for Computational Biology informatics had clearly arrived. In conferences were sufficiently successful (ISCB), a partnership that was formed addition to the founding of ISCB, 1996 to create a financial nest egg that was during the Journal’s conception in saw the sequencing of the first genome used each year to start the process of 2005. With ISCB being the only of a free-living organism (yeast) and planning and executing the next year’s international body representing Affymetrix’s release of its first meeting. Initially, relatively modest computational biologists, it made commercial DNA chip. checks were cut and sent from one perfect sense for PLoS Computational The hot topics in bioinformatics organizer to another informally. As the Biology to be closely affiliated. The circa 1996, at least as reflected by the size of these checks increased, the Society had to take more of a chance conference on Intelligent Systems for organizers (and their home than similar societies, choosing to step Molecular Biology (ISMB) at institutions) became increasingly away from an existing financially Washington University in St. Louis, uncomfortable exchanging them beneficial subscription journal to align included issues which have largely been informally, and decided that they with an open access publication as a solved (such as gene finding or needed an organization—thus, ISCB.
    [Show full text]
  • Biocuration 2016 - Posters
    Biocuration 2016 - Posters Source: http://www.sib.swiss/events/biocuration2016/posters 1 RAM: A standards-based database for extracting and analyzing disease-specified concepts from the multitude of biomedical resources Jinmeng Jia and Tieliu Shi Each year, millions of people around world suffer from the consequence of the misdiagnosis and ineffective treatment of various disease, especially those intractable diseases and rare diseases. Integration of various data related to human diseases help us not only for identifying drug targets, connecting genetic variations of phenotypes and understanding molecular pathways relevant to novel treatment, but also for coupling clinical care and biomedical researches. To this end, we built the Rare disease Annotation & Medicine (RAM) standards-based database which can provide reference to map and extract disease-specified information from multitude of biomedical resources such as free text articles in MEDLINE and Electronic Medical Records (EMRs). RAM integrates disease-specified concepts from ICD-9, ICD-10, SNOMED-CT and MeSH (http://www.nlm.nih.gov/mesh/MBrowser.html) extracted from the Unified Medical Language System (UMLS) based on the UMLS Concept Unique Identifiers for each Disease Term. We also integrated phenotypes from OMIM for each disease term, which link underlying mechanisms and clinical observation. Moreover, we used disease-manifestation (D-M) pairs from existing biomedical ontologies as prior knowledge to automatically recognize D-M-specific syntactic patterns from full text articles in MEDLINE. Considering that most of the record-based disease information in public databases are textual format, we extracted disease terms and their related biomedical descriptive phrases from Online Mendelian Inheritance in Man (OMIM), National Organization for Rare Disorders (NORD) and Orphanet using UMLS Thesaurus.
    [Show full text]
  • Scalable Approaches for Auditing the Completeness of Biomedical Ontologies
    University of Kentucky UKnowledge Theses and Dissertations--Computer Science Computer Science 2021 Scalable Approaches for Auditing the Completeness of Biomedical Ontologies Fengbo Zheng University of Kentucky, [email protected] Author ORCID Identifier: https://orcid.org/0000-0001-5902-0186 Digital Object Identifier: https://doi.org/10.13023/etd.2021.128 Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Zheng, Fengbo, "Scalable Approaches for Auditing the Completeness of Biomedical Ontologies" (2021). Theses and Dissertations--Computer Science. 105. https://uknowledge.uky.edu/cs_etds/105 This Doctoral Dissertation is brought to you for free and open access by the Computer Science at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Computer Science by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known.
    [Show full text]
  • Pacific Symposium on Biocomputing 2008
    PACIFIC SYMPOSIUM ON BIOCOMPUTING 2008 This year, PSB returns to its most common venue, the Fairmont Orchid on the Big Island of Hawaii. We are now in our thirteenth year, and had a record number of both proposed sessions (we accepted 9) as well as submissions to the conference this year (150). Many sessions at PSB have a lifetime of approximately three years. The first year is a test of the interest in the field, and the ability to attract a critical mass of papers. With success, the second year is usually a larger, more competitive session. The third (and rarely fourth years) usually come as the subdiscipline is recognized at the general biocomputing meetings such as ISMB, RECOMB and others, and often this is when the PSB organizers conclude that their work is done, and the session can be “retired.” PSB aficionados will notice new sessions this year in next-generation sequencing, tiling array analysis, multiscale modeling, small regulatory RNAs, and other areas. The richness of exciting new areas has led us to have more total sessions, and thus the average session size is smaller. We consider this an experiment, and look forward to seeing how it goes. We would like to thank our keynote speakers. Dr. Andrew McCulloch, Professor and Chair, Department of Bioengineering, University of California, San Diego, will talk about “Systems biology and multi-scale modeling of the heart.” Our keynote in the area of Ethical, Legal and Social implications of technology will be John Dupre, Director of Egenis (ESRC Centre for Genomics in Society) and Professor of Philosophy of Science, University of Exeter.
    [Show full text]
  • 2016 National Library of Medicine Informatics Training Confernece
    National Library of Medicine Informatics Training Conference June 27-28, 2016 The Ohio State University The Ohio Union Columbus, Ohio TABLE OF CONTENTS Agenda ..................................................................................................................................................... 1 Day 1 in Detail ......................................................................................................................................... 1 Day 2 in Detail ......................................................................................................................................... 6 Attendee and Presenter Information Full Training Conference Attendee and Presenters List ......................................................................... 9 Administrative Contacts for Each Program ............................................................................................. 13 Plenary/Focus Session Presentations List ................................................................................................ 14 Poster Presentations List ......................................................................................................................... 15 Open Mic Presentations List .................................................................................................................... 17 Abstracts for Presentations and Posters ....................................................................................... 19 Plenary Sessions (Days 1 and 2) Day 1 Plenary Session #1 ......................................................................................................................
    [Show full text]
  • Pacific Symposium on Biocomputing 2020 January 3-7, 2020 Big Island of Hawaii
    Pacific Symposium on Biocomputing 2020 January 3-7, 2020 Big Island of Hawaii Program Book PACIFIC SYMPOSIUM ON BIOCOMPUTING 2020 Big Island of Hawaii, January 3-7, 2020 Welcome to PSB 2020! We have prepared this program book to give you quick access to information you need for PSB 2020. Enclosed you will find: • Logistics information • Medical services information • Full conference schedule (see website for the latest version) • Agendas for workshops and JBrowse demo • Call for Session and Workshop Proposals for PSB 2021 • Poster/abstract titles and author index • Participant list The latest conference materials are available online at http://psb.stanford.edu/conference-materials/. PSB 2020 gratefully acknowledges the support of the Cleveland Institute for Computational Biology; UPenn Institute for Biomedical Informatics; Variant Bio; Penn Center for Precision Medicine, Penn Medicine; Cipherome; Translational Bioinformatics Conference (TBC); the National Institutes of Health (NIH); and the International Society for Computational Biology (ISCB). If you or your institution are interested in sponsoring, PSB, please contact Tiffany Murray at [email protected] If you have any questions, the PSB registration staff (Tiffany Murray, Kasey Miller, BJ Morrison-McKay, and Cindy Paulazzo) are happy to help you. Aloha! Russ Altman Keith Dunker Larry Hunter Teri Klein Maryln Ritchie The PSB 2020 Organizers PACIFIC SYMPOSIUM ON BIOCOMPUTING 2020 Big Island of Hawaii, January 3-7, 2020 SPEAKER INFORMATION Oral presentations of accepted proceedings papers will take place in Salon 2 & 3. Speakers are allotted 10 minutes for presentation and 5 minutes for questions for a total of 15 minutes. Instructions for uploading talks were sent to authors with oral presentations.
    [Show full text]
  • I S C B N E W S L E T T
    ISCB NEWSLETTER FOCUS ISSUE {contents} President’s Letter 2 Member Involvement Encouraged Register for ISMB 2002 3 Registration and Tutorial Update Host ISMB 2004 or 2005 3 David Baker 4 2002 Overton Prize Recipient Overton Endowment 4 ISMB 2002 Committees 4 ISMB 2002 Opportunities 5 Sponsor and Exhibitor Benefits Best Paper Award by SGI 5 ISMB 2002 SIGs 6 New Program for 2002 ISMB Goes Down Under 7 Planning Underway for 2003 Hot Jobs! Top Companies! 8 ISMB 2002 Job Fair ISCB Board Nominations 8 Bioinformatics Pioneers 9 ISMB 2002 Keynote Speakers Invited Editorial 10 Anna Tramontano: Bioinformatics in Europe Software Recommendations11 ISCB Software Statement volume 5. issue 2. summer 2002 Community Development 12 ISCB’s Regional Affiliates Program ISCB Staff Introduction 12 Fellowship Recipients 13 Awardees at RECOMB 2002 Events and Opportunities 14 Bioinformatics events world wide INTERNATIONAL SOCIETY FOR COMPUTATIONAL BIOLOGY A NOTE FROM ISCB PRESIDENT This newsletter is packed with information on development and dissemination of bioinfor- the ISMB2002 conference. With over 200 matics. Issues arise from recommendations paper submissions and over 500 poster submis- made by the Society’s committees, Board of sions, the conference promises to be a scientific Directors, and membership at large. Important feast. On behalf of the ISCB’s Directors, staff, issues are defined as motions and are discussed EXECUTIVE COMMITTEE and membership, I would like to thank the by the Board of Directors on a bi-monthly Philip E. Bourne, Ph.D., President organizing committee, local organizing com- teleconference. Motions that pass are enacted Michael Gribskov, Ph.D., mittee, and program committee for their hard by the Executive Committee which also serves Vice President work preparing for the conference.
    [Show full text]
  • Simulation and Graph Mining Tools for Improving Gene Mapping Efficiency
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Helsingin yliopiston digitaalinen arkisto DEPARTMENT OF COMPUTER SCIENCE SERIES OF PUBLICATIONS A REPORT A-2011-3 Simulation and graph mining tools for improving gene mapping efficiency Petteri Hintsanen To be presented, with the permission of the Faculty of Science of the University of Helsinki, for public criticism in Auditorium XIV (Univer- sity Main Building, Unioninkatu 34) on 30 September 2011 at twelve o’clock noon. UNIVERSITY OF HELSINKI FINLAND Supervisor Hannu Toivonen, University of Helsinki, Finland Pre-examiners Tapio Salakoski, University of Turku, Finland Janne Nikkila,¨ University of Helsinki, Finland Opponent Michael Berthold, Universitat¨ Konstanz, Germany Custos Hannu Toivonen, University of Helsinki, Finland Contact information Department of Computer Science P.O. Box 68 (Gustaf Hallstr¨ omin¨ katu 2b) FI-00014 University of Helsinki Finland Email address: [email protected].fi URL: http://www.cs.Helsinki.fi/ Telephone: +358 9 1911, telefax: +358 9 191 51120 Copyright c 2011 Petteri Hintsanen ISSN 1238-8645 ISBN 978-952-10-7139-3 (paperback) ISBN 978-952-10-7140-9 (PDF) Computing Reviews (1998) Classification: G.2.2, G.3, H.2.5, H.2.8, J.3 Helsinki 2011 Helsinki University Print Simulation and graph mining tools for improving gene mapping efficiency Petteri Hintsanen Department of Computer Science P.O. Box 68, FI-00014 University of Helsinki, Finland petteri.hintsanen@iki.fi http://iki.fi/petterih PhD Thesis, Series of Publications A, Report A-2011-3 Helsinki, September 2011, 136 pages ISSN 1238-8645 ISBN 978-952-10-7139-3 (paperback) ISBN 978-952-10-7140-9 (PDF) Abstract Gene mapping is a systematic search for genes that affect observable character- istics of an organism.
    [Show full text]
  • Emidio Capriotti Phd CURRICULUM VITÆ
    Emidio Capriotti PhD CURRICULUM VITÆ Name: Emidio Capriotti Nationality: Italian Date of birth: February, 1973 Place of birth: Roma, Italy Languages: Italian, English, Spanish Positions Oct 2019 Associate Professor: Department of Pharmacy and Biotechnology (FaBiT). University of Bologna, Bologna, Italy 2016-2019 Senior Assistant Professor (RTD type B): Department of Pharmacy and Biotechnology (FaBiT) and Department of Biological, Geological, and Environmental Sciences (BiGeA). University of Bologna, Bologna, Italy. 2015-2016 Junior Group Leader: Institute of Mathematical Modeling of Biological Systems, University of Düsseldorf, Düsseldorf, Germany 2012-2015 Assistant Professor: Division of Informatics, Department of Pathology, University of Alabama at Birmingham (UAB), Birmingham (AL), USA. 2011-2012 Marie-Curie IOF: Contracted Researcher at the Department of Mathematics and Computer Science, University of Balearic Islands (UIB), Palma de Mallorca, Spain. 2009-2011 Marie-Curie IOF: Postdoctoral Researcher at the Helix Group, Department of Bioengineering, Stanford University, Stanford (CA), USA. 2006-2009 Postdoctoral Researcher in the Structural Genomics Group at Department of Bioinformatics and Genetics, Prince Felipe Research Center (CIPF) Valencia, Spain. 2004-2006 Contract researcher at Department of Biology, University of Bologna, Bologna, Italy. 2001-2003 Ph.D student in Physical Sciences at University of Bologna, Bologna, Italy. Education Sep 2004 Master in Bioinformatics (first level) University of Bologna, Bologna (Italy). Jun 2004 Ph.D. in Physical Sciences University of Bologna, Bologna (Italy). Jul 1999 Laurea (B.S.) Degree in Physical Sciences, score 106/110 University of Bologna, Bologna (Italy). Visiting Jun 2012 – Jul 2012 Prof. Frederic Rousseau and Prof. Joost Schymkowitz, VIB Switch Laboratory, KU Leuven, Leuven (Belgium) May 2009 Prof.
    [Show full text]