Research Report 2018
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STRING V10: Protein–Protein Interaction Networks, Integrated
Published online 28 October 2014 Nucleic Acids Research, 2015, Vol. 43, Database issue D447–D452 doi: 10.1093/nar/gku1003 STRING v10: protein–protein interaction networks, integrated over the tree of life Damian Szklarczyk1, Andrea Franceschini1, Stefan Wyder1, Kristoffer Forslund2, Davide Heller1, Jaime Huerta-Cepas2, Milan Simonovic1, Alexander Roth1, Alberto Santos3, Kalliopi P. Tsafou3, Michael Kuhn4,5, Peer Bork2,*, Lars J. Jensen3,* and Christian von Mering1,* 1Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich, 8057 Zurich, Switzerland, 2European Molecular Biology Laboratory, 69117 Heidelberg, Germany, 3Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen N, Denmark, 4Biotechnology Center, Technische Universitat¨ Dresden, 01062 Dresden, Germany and 5Max Planck Institute of Molecular Cell Biology and Downloaded from Genetics, 01062 Dresden, Germany Received September 15, 2014; Accepted October 07, 2014 ABSTRACT INTRODUCTION http://nar.oxfordjournals.org/ The many functional partnerships and interactions For a full description of a protein’s function, knowledge that occur between proteins are at the core of cel- about its specific interaction partners is an important pre- lular processing and their systematic characteriza- requisite. The concept of protein ‘function’ is somewhat hi- tion helps to provide context in molecular systems erarchical (1–4), and at all levels in this hierarchy, interac- biology. However, known and predicted interactions tions between proteins help to describe and narrow down a protein’s function: its three-dimensional structure may are scattered over multiple resources, and the avail- become meaningful only in the context of a larger pro- able data exhibit notable differences in terms of qual- tein assembly, its molecular actions may be regulated by at University of Aarhus on January 22, 2015 ity and completeness. -
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 . -
Research Report 2006 Max Planck Institute for Molecular Genetics, Berlin Imprint | Research Report 2006
MAX PLANCK INSTITUTE FOR MOLECULAR GENETICS Research Report 2006 Max Planck Institute for Molecular Genetics, Berlin Imprint | Research Report 2006 Published by the Max Planck Institute for Molecular Genetics (MPIMG), Berlin, Germany, August 2006 Editorial Board Bernhard Herrmann, Hans Lehrach, H.-Hilger Ropers, Martin Vingron Coordination Claudia Falter, Ingrid Stark Design & Production UNICOM Werbeagentur GmbH, Berlin Number of copies: 1,500 Photos Katrin Ullrich, MPIMG; David Ausserhofer Contact Max Planck Institute for Molecular Genetics Ihnestr. 63–73 14195 Berlin, Germany Phone: +49 (0)30-8413 - 0 Fax: +49 (0)30-8413 - 1207 Email: [email protected] For further information about the MPIMG please see our website: www.molgen.mpg.de MPI for Molecular Genetics Research Report 2006 Table of Contents The Max Planck Institute for Molecular Genetics . 4 • Organisational Structure. 4 • MPIMG – Mission, Development of the Institute, Research Concept. .5 Department of Developmental Genetics (Bernhard Herrmann) . 7 • Transmission ratio distortion (Hermann Bauer) . .11 • Signal Transduction in Embryogenesis and Tumor Progression (Markus Morkel). 14 • Development of Endodermal Organs (Heiner Schrewe) . 16 • Gene Expression and 3D-Reconstruction (Ralf Spörle). 18 • Somitogenesis (Lars Wittler). 21 Department of Vertebrate Genomics (Hans Lehrach) . 25 • Molecular Embryology and Aging (James Adjaye). .31 • Protein Expression and Protein Structure (Konrad Büssow). .34 • Mass Spectrometry (Johan Gobom). 37 • Bioinformatics (Ralf Herwig). .40 • Comparative and Functional Genomics (Heinz Himmelbauer). 44 • Genetic Variation (Margret Hoehe). 48 • Cell Arrays/Oligofingerprinting (Michal Janitz). .52 • Kinetic Modeling (Edda Klipp) . .56 • In Vitro Ligand Screening (Zoltán Konthur). .60 • Neurodegenerative Disorders (Sylvia Krobitsch). .64 • Protein Complexes & Cell Organelle Assembly/ USN (Bodo Lange/Thorsten Mielke). .67 • Automation & Technology Development (Hans Lehrach). -
Reactome Pathway Analysis
Fabregat et al. BMC Bioinformatics (2017) 18:142 DOI 10.1186/s12859-017-1559-2 SOFTWARE Open Access Reactome pathway analysis: a high- performance in-memory approach Antonio Fabregat1,2, Konstantinos Sidiropoulos1, Guilherme Viteri1, Oscar Forner1, Pablo Marin-Garcia3,4, Vicente Arnau5,6, Peter D’Eustachio7, Lincoln Stein8,9 and Henning Hermjakob1,10* Abstract Background: Reactome aims to provide bioinformatics tools for visualisation, interpretation and analysis of pathway knowledge to support basic research, genome analysis, modelling, systems biology and education. Pathway analysis methods have a broad range of applications in physiological and biomedical research; one of the main problems, from the analysis methods performance point of view, is the constantly increasing size of the data samples. Results: Here, we present a new high-performance in-memory implementation of the well-established over- representation analysis method. To achieve the target, the over-representation analysis method is divided in four different steps and, for each of them, specific data structures are used to improve performance and minimise the memory footprint. The first step, finding out whether an identifier in the user’s sample corresponds to an entity in Reactome, is addressed using a radix tree as a lookup table. The second step, modelling the proteins, chemicals, their orthologous in other species and their composition in complexes and sets, is addressed with a graph. The third and fourth steps, that aggregate the results and calculate the statistics, are solved with a double-linked tree. Conclusion: Through the use of highly optimised, in-memory data structures and algorithms, Reactome has achieved a stable, high performance pathway analysis service, enabling the analysis of genome-wide datasets within seconds, allowing interactive exploration and analysis of high throughput data. -
Next Generation Machine Learning Prediction of Protein Cellular Sorting
TECHNISCHE UNIVERSITÄT MÜNCHEN Lehrstuhl für Bioinformatik Next Generation Machine Learning Prediction of Protein Cellular Sorting Tatyana Goldberg Vollständiger Abdruck der von der Fakultät für Informatik der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. Daniel Cremers Prüfer der Dissertation: 1. Univ.-Prof. Dr. Burkhard Rost 2. Prof. Dr. Yana Bromberg, The State University of New Jersey/USA 3. Univ.-Prof. Dr. Iris Antes Die Dissertation wurde am 15.12.2015 bei der Technischen Universität München eingereicht und durch die Fakultät für Informatik am 22.03.2016 angenommen. ii Table of Contents Abstract ............................................................................................................................................. v Zusammenfassung ........................................................................................................................... vii Acknowledgments ............................................................................................................................ ix List of publications ........................................................................................................................... xi List of Figures and Tables ............................................................................................................... xiii 1. Introduction ............................................................................................................................... -
First Analysis Steps
FirstFirst analysisanalysis stepssteps o quality control and optimization o calibration and error modeling o data transformations Wolfgang Huber Dep. of Molecular Genome Analysis (A. Poustka) DKFZ Heidelberg Acknowledgements Anja von Heydebreck Günther Sawitzki Holger Sültmann, Klaus Steiner, Markus Vogt, Jörg Schneider, Frank Bergmann, Florian Haller, Katharina Finis, Stephanie Süß, Anke Schroth, Friederike Wilmer, Judith Boer, Martin Vingron, Annemarie Poustka Sandrine Dudoit, Robert Gentleman, Rafael Irizarry and Yee Hwa Yang: Bioconductor short course, summer 2002 and many others a microarray slide Slide: 25x75 mm Spot-to-spot: ca. 150-350 µm 4 x 4 or 8x4 sectors 17...38 rows and columns per sector ca. 4600…46000 probes/array sector: corresponds to one print-tip Terminology sample: RNA (cDNA) hybridized to the array, aka target, mobile substrate. probe: DNA spotted on the array, aka spot, immobile substrate. sector: rectangular matrix of spots printed using the same print-tip (or pin), aka print-tip-group plate: set of 384 (768) spots printed with DNA from the same microtitre plate of clones slide, array channel: data from one color (Cy3 = cyanine 3 = green, Cy5 = cyanine 5 = red). batch: collection of microarrays with the same probe layout. Raw data scanner signal resolution: 5 or 10 mm spatial, 16 bit (65536) dynamical per channel ca. 30-50 pixels per probe (60 µm spot size) 40 MB per array Raw data scanner signal resolution: 5 or 10 mm spatial, 16 bit (65536) dynamical per channel ca. 30-50 pixels per probe (60 µm spot size) 40 MB per array Image Analysis Raw data scanner signal resolution: 5 or 10 mm spatial, 16 bit (65536) dynamical per channel ca. -
Probabilistic Models for Gene Silencing Data
Probabilistic Models for Gene Silencing Data Florian Markowetz Dezember 2005 Dissertation zur Erlangung des Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) am Fachbereich Mathematik und Informatik der Freien Universit¨atBerlin 1. Referent: Prof. Dr. Martin Vingron 2. Referent: Prof. Dr. Klaus-Robert M¨uller Tag der Promotion: 26. April 2006 Preface Acknowledgements This work was carried out in the Computational Diagnostics group of the Department of Computational Molecular Biology at the Max Planck Institute for Molecular Genetics in Berlin. I thank all past and present colleagues for the good working atmosphere and the scientific—and sometimes maybe not so scientific—discussions. Especially, I am grateful to my supervisor Rainer Spang for suggesting the topic, his scientific support, and the opportunity to write this thesis under his guidance. I thank Michael Boutros for providing the expression data and for introducing me to the world of RNAi when I visited his lab at the DKFZ in Heidelberg. I thank Anja von Heydebreck, J¨org Schultz, and Martin Vingron for their advice and counsel as members of my PhD commitee. During the time I worked on this thesis, I enjoyed fruitful discussions with many people. In particular, I gratefully acknowledge Jacques Bloch, Steffen Grossmann, Achim Tresch, and Chen-Hsiang Yeang for their contributions. Special thanks go to Viola Gesellchen, Britta Koch, Stefanie Scheid, Stefan Bentink, Stefan Haas, Dennis Kostka, and Stefan R¨opcke, who read drafts of this thesis and greatly improved it by their comments. Publications Parts of this thesis have been published before. Chapter 2 grew out of lectures I gave in 2005 at the Instiute for Theoretical Physics and Mathematics (IPM) in Tehran, Iran, and at the German Conference on Bioinformatics (GCB), Hamburg, Germany. -
15Th International Symposium on Bioinformatics Research and Applications
ISBRA 2019 15th International Symposium on Bioinformatics Research and Applications June 3–6, 2019 Technical University of Catalonia Barcelona, Spain http://alan.cs.gsu.edu/isbra19/ About the Technical University of Catalonia The Technical University of Catalonia (UPC) is a public institution of Higher Education and Research, specialized in the areas of Architecture, Engineering, Science and Technology. The UPC has a wide spread presence in Catalonia, with nine campuses located in Barcelona and nearby towns. The campuses are accessible, well connected by public transport and equipped with the necessary facilities and services to contribute to learning, research and university life. Founded in 1968 by grouping together existing state technical schools of Architecture and Engineering in Barcelona, which date back from the mid-19th century, it gained university status in 1971. The UPC today has a student population of over 30,000, with more than 3,000 teaching and research staff and about 2,000 administrative and service staff. There are 64 bachelor’s degrees, 68 master’s degrees, and 46 doctoral programs offered by 20 schools. Further, there are 50 international double-degree agreements with 30 universities, and about 3,000 students in international mobility programs. Research teams generate e60 million in annual funding, with a total budget of about e300 million. About the Department of Computer Science The Department of Computer Science was created in 1987 and is one of the largest depart- ments at the UPC. It has about 90 full-time faculty and 50 Ph.D. students. The Department is responsible for teaching and research in several disciplines related to the foundations of computing and their applications. -
Research Report 2009 Max Planck Institute for Molecular Genetics, Berlin Imprint | Research Report 2009
Research Report 2009 Max Planck Institute for Molecular Genetics, Berlin Imprint | Research Report 2009 Published by the Max Planck Institute for Molecular Genetics (MPIMG), Berlin, Germany, December 2009 Editorial Board: B.G. Herrmann, H. Lehrach, H.-H. Ropers, M. Vingron Conception & coordination: Patricia Marquardt Photography: Katrin Ullrich, MPIMG; David Ausserhofer Scientific Illustrations: MPIMG Production: Thomas Didier, Meta Data Contact: Max Planck Institute for Molecular Genetics Ihnestr. 63 – 73 14195 Berlin Germany Phone: +49 (0)30 8413-0 Fax: +49 (0)30 8413-1207 Email: [email protected] For further information about the MPIMG, please visit http://www.molgen.mpg.de MPI for Molecular Genetics Research Report 2009 Research Report 2009 1 Max Planck Institute for Molecular Genetics Berlin, December 2009 The Max Planck Institute for Molecular Genetics 2 MPI for Molecular Genetics Research Report 2009 Table of contents Organisational structure . 6 The Max Planck Institute for Molecular Genetics . 7 Mission . 7 Development of the Institute. 7 Research Concept . 8 Department of Developmental Genetics (Bernhard Herrmann) . 9 Transmission ratio distortion (H. Bauer) . 13 Regulatory Networks of Mesoderm Formation & Somitogenesis (B. Herrmann) . 17 Signal Transduction in Embryogenesis and Tumour Progression (M. Morkel) . 22 Organogenesis (H. Schrewe) . 26 General information about the whole Department . 29 Department of Vertebrate Genomics (Hans Lehrach) . 33 Molecular Embryology and Aging (J. Adjaye) . 40 Neuropsychiatric Genetics (L. Bertram) . 46 Automation (A. Dahl, W. Nietfeld, H. Seitz) . 49 Nucleic Acid-based Technologies (J. Glökler) . 55 Bioinformatics (R. Herwig) . 60 Comparative and Functional Genomics (H. Himmelbauer) . .65 Genetic Variation, Haplotypes & Genetics of Complex Diseases (M. Hoehe) . 69 3 in vitro Ligand Screening (Z. -
Network-Based Association of Hypoxia-Responsive Genes with Cardiovascular Diseases
Network-based association of hypoxia-responsive genes with cardiovascular diseases Rui-Sheng Wang, William M Oldham and Joseph Loscalzo Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA E-mail: [email protected] Received 19 May 2014, revised 21 July 2014 Accepted for publication 11 August 2014 Published 24 October 2014 New Journal of Physics 16 (2014) 105014 doi:10.1088/1367-2630/16/10/105014 Abstract Molecular oxygen is indispensable for cellular viability and function. Hypoxia is a stress condition in which oxygen demand exceeds supply. Low cellular oxygen content induces a number of molecular changes to activate regulatory pathways responsible for increasing the oxygen supply and optimizing cellular metabolism under limited oxygen conditions. Hypoxia plays critical roles in the pathobiol- ogy of many diseases, such as cancer, heart failure, myocardial ischemia, stroke, and chronic lung diseases. Although the complicated associations between hypoxia and cardiovascular (and cerebrovascular) diseases (CVD) have been recognized for some time, there are few studies that investigate their biological link from a systems biology perspective. In this study, we integrate hypoxia genes, CVD genes, and the human protein interactome in order to explore the relationship between hypoxia and cardiovascular diseases at a systems level. We show that hypoxia genes are much closer to CVD genes in the human protein interactome than that expected by chance. We also find that hypoxia genes play significant bridging roles in connecting different cardiovascular diseases. We construct a hypoxia-CVD bipartite network and find several interesting hypoxia- CVD modules with significant gene ontology similarity. Finally, we show that hypoxia genes tend to have more CVD interactors in the human interactome than in random networks of matching topology. -
Biomolecule and Bioentity Interaction Databases in Systems Biology: a Comprehensive Review
biomolecules Review Biomolecule and Bioentity Interaction Databases in Systems Biology: A Comprehensive Review Fotis A. Baltoumas 1,* , Sofia Zafeiropoulou 1, Evangelos Karatzas 1 , Mikaela Koutrouli 1,2, Foteini Thanati 1, Kleanthi Voutsadaki 1 , Maria Gkonta 1, Joana Hotova 1, Ioannis Kasionis 1, Pantelis Hatzis 1,3 and Georgios A. Pavlopoulos 1,3,* 1 Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center “Alexander Fleming”, 16672 Vari, Greece; zafeiropoulou@fleming.gr (S.Z.); karatzas@fleming.gr (E.K.); [email protected] (M.K.); [email protected] (F.T.); voutsadaki@fleming.gr (K.V.); [email protected] (M.G.); hotova@fleming.gr (J.H.); [email protected] (I.K.); hatzis@fleming.gr (P.H.) 2 Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen, Denmark 3 Center for New Biotechnologies and Precision Medicine, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece * Correspondence: baltoumas@fleming.gr (F.A.B.); pavlopoulos@fleming.gr (G.A.P.); Tel.: +30-210-965-6310 (G.A.P.) Abstract: Technological advances in high-throughput techniques have resulted in tremendous growth Citation: Baltoumas, F.A.; of complex biological datasets providing evidence regarding various biomolecular interactions. Zafeiropoulou, S.; Karatzas, E.; To cope with this data flood, computational approaches, web services, and databases have been Koutrouli, M.; Thanati, F.; Voutsadaki, implemented to deal with issues such as data integration, visualization, exploration, organization, K.; Gkonta, M.; Hotova, J.; Kasionis, scalability, and complexity. Nevertheless, as the number of such sets increases, it is becoming more I.; Hatzis, P.; et al. Biomolecule and and more difficult for an end user to know what the scope and focus of each repository is and how Bioentity Interaction Databases in redundant the information between them is. -
The 2021 Update of the EPA's Adverse Outcome Pathway Database
www.nature.com/scientificdata OPEN The 2021 update of the EPA’s Data DescRiptor adverse outcome pathway database Holly M. Mortensen1 ✉ , Jonathan Senn2, Trevor Levey2,3, Phillip Langley2,4 & Antony J. Williams5 The EPA developed the Adverse Outcome Pathway Database (AOP-DB) to better characterize adverse outcomes of toxicological interest that are relevant to human health and the environment. Here we present the most recent version of the EPA Adverse Outcome Pathway Database (AOP-DB), version 2. AOP-DB v.2 introduces several substantial updates, which include automated data pulls from the AOP-Wiki 2.0, the integration of tissue-gene network data, and human AOP-gene data by population, semantic mapping and SPARQL endpoint creation, in addition to the presentation of the frst publicly available AOP-DB web user interface. Potential users of the data may investigate specifc molecular targets of an AOP, the relation of those gene/protein targets to other AOPs, cross-species, pathway, or disease-AOP relationships, or frequencies of AOP-related functional variants in particular populations, for example. Version updates described herein help inform new testable hypotheses about the etiology and mechanisms underlying adverse outcomes of environmental and toxicological concern. Background & Summary Tere is a need for approaches to understand the biological mechanism of adverse outcomes and human varia- bility in response to environmental chemical exposure. A recent legislation, the Frank R. Lautenberg Chemical Safety for the twenty-frst Century Act of 20161, requires the US Environmental Protection Agency to evaluate new and existing toxic chemicals with explicit consideration of susceptible populations of all types (life stage, exposure, genetic, etc.).