DOCSLIB.ORG

SBC Annual Report

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
SBC Annual Report Stockholm Bioinformatics Centre Annual Report 2007 Director’s summary 2007 was a stable year for SBC – no major positions were vacated or filled, nor did any major relocations or other big environment changes occur. A steady production of science resulted in 33 publications, including important contributions in top journals such as Nature, Science, and PNAS. Four PhD theses were defended (Elias, Melén, Viklund, Granseth), and at the Frescati campus one workshop and one symposium were organized. Collaborations with experimental groups at KTH School of Biotechnology and SU Department of Biochemistry and Biophysics (DBB) are on-going. SBC is involved in several grant applications with external groups at KTH and SU, notably two Linnaeus grants at VR. A new web server machine was set up at SBC during 2007 in order to relieve the main www server, and eleven virtual servers were installed on it. These include bioinformation databases (InParanoid, FunCoup, Pfam, Humanoid), protein function/structure prediction servers (Phobius, Sfinx, GPCRHMM), sequence analysis tools (jSquid, Sfixem, MSA), and DAS services for protein transmembrane topology prediction (See Computer Infrastructure). In total about 40 web servers are now hosted, which makes the SBC a major contributor of bioinformatics resources internationally. As a result of the Bologna process, the SBC has been involved in developing Master programmes in bioinformatics and computational biology. Building on existing courses and 1 adding new ones (see Courses), two programmes have been set up. At KTH for a Master in Computational and Systems Biology, and at SU for a Master in Bioinformatics. The KTH programme will start in the fall of 2008 while the SU programme started in the fall of 2007. Here fourteen students, all of foreign nationality, were registered and have been learning bioinformatics techniques both via lectures and hands-on work in a new computer lab with twelve Linux workstations. Although this is a small start, we hope that it marks the beginning of a blossoming curriculum that will provide a steady stream of talented bioinformaticians for the future. The KTH and SU programmes have different focus, but several courses are common. The SBC thus serves as a hub to find synergies and cross-fertilize the bioinformatics education and research between the two universities. Personnel during 2007: Prof. Arne Elofsson Åsa Björklund PhD student Diana Ekman PhD student Olivia Eriksson PhD student Johannes Frey-Skött PhD student Linnea Hedin PhD student Kristoffer Illergård PhD student Per Larsson PhD student Håkan Viklund* PhD student Erik Granseth* PhD student Prof. Jens Lagergren Öjvind Johansson Post-doc Ali Tofigh PhD student Örjan Åkerborg PhD student Isaac Elias* PhD student Ass. Prof. Erik Lindahl Anna Johansson PhD student Aron Hennerdal PhD student Pär Bjelkmar PhD student Jenny Falk PhD student Yana Vereshchaga Post-doc Prof. Gunnar von Heijne Andreas Bernsel PhD student Karin Melen* PhD student Prof. Erik Sonnhammer (Director of the SBC) Andrey Alexeyenko Post-doc Olof Karlberg* Post-doc Mats Lindskog* Post-doc Kristoffer Forslund PhD student Anna Henricson PhD student Gabriel Östlund PhD student Bengt Sennblad Assistant professor 2 Lars Arvestad Senior scientist Olof Emanuelsson Research associate Karin Julenius Assistant professor Erik Sjölund System administrator *) Left during 2007 Collaboration partners SU Molecular Biology & Functional Genomics (Prof. Marie Öhman) KTH Biotechnology (Prof. Tuula Teeri, Prof. Peter Savolainen, and Prof. Mathias Uhlén) KI CMM (Prof. Gunnar Norstedt) Center for Biological Sequence Analysis, Danmarks Tekniska Universitet (Prof. Søren Brunak & Dr. Anders Gorm Pedersen) Bioinformatics Center, Köpenhamns Universitet (Prof. Anders Krogh) Bioinformatics Laboratory, BioInfoBank Institute, Poznan (Dr. Leszek Rychlewski) Institut Pasteur, Paris (Dr. Marc Delarue) Stanford University (Prof. Michael Levitt, Prof. Vijay S. Pande, Prof. James Trudell) Uppsala University (Dr. van der Spoel) University of Wyoming (Dr. David Liberles) McGill Centre for Bioinformatics (Dr. Mike Hallett) University of British Columbia (Dr. Wyeth Wasserman). Yale University, New Haven, CT. (Dr. Mark Gerstein) University of Buffalo (Dr. Daniel Fischer) Cornell University, Ithaca, NY. (Dr. Klaas van Wijk) The Pfam database consortium (Dr. Richard Durbin, Sanger Institute; Prof. Sean Eddy, Janelia farm, VA, USA) University of Valencia, Spain (Dr. Gustavo Camps-Valls) University of Rochester Medical Center (Dr. Fred Hagen) University of Paris René Descartes (Prof. Jean-Laurent Casanova) LU Clinical Genetics (Mattias Höglund) Max Planck Inst. für Genetik, Berlin. (Alexander Schliep) EU bioinformatics network Biosapiens EU bioinformatics network Embrace EU bioinformatics network Genefun Scientific publications 2007 was a very fruitful year for SBC in terms of publications. Papers were published in top journals such as Nature, Science, PNAS, and Genome Research. Many of them represent collaborations with experimental groups, testifying to SBC's ability to apply new computational techniques to real-world biological problems. Being part of the ENCODE consortium for detailed analysis of the genome adds competence to the SBC that is valuable to many neighboring experimental groups, for instance KTH-biotechnology. From http://www.sbc.su.se/publications: Hessa, T., Meindl-Beinker, N.M., Bernsel, A., Kim, H., Sato, Y., Lerch-Bader, M., Nilsson, I., White, S.H. and von Heijne, G. (2007) Molecular code for transmembrane-helix recognition by the Sec61 translocon. Nature 450 (7172) : 1026-1030. 3 Xie, K., Hessa, T., Seppala, S., Rapp, M., Heijne, G. and Dalbey, R.E. (2007) Features of transmembrane segments that promote the lateral release from the translocase into the lipid phase. Biochemistry 46 (51) : 15153-15161. Lundin, C., Kall, L., Kreher, S.A., Kapp, K., Sonnhammer, E.L., Carlson, J.R., Heijne, G. and Nilsson, I. (2007) Membrane topology of the Drosophila OR83b odorant receptor. FEBS Lett 581 (29) : 5601-5604. Hollich, V. and Sonnhammer, E.L. (2007) PfamAlyzer: domain-centric homology search. Bioinformatics 23 (24) : 3382-3383. Wallner, B. and Elofsson, A. (2007) Prediction of global and local model quality in CASP7 using Pcons and ProQ. Proteins 69 (S8) : 184-193. Granseth, E., Seppala, S., Rapp, M., Daley, D.O. and Von Heijne, G. (2007) Membrane protein structural biology - How far can the bugs take us? (Review). Mol Membr Biol 24 (5) : 329-332. Newstead, S., Kim, H., von Heijne, G., Iwata, S. and Drew, D. (2007) High-throughput fluorescent-based optimization of eukaryotic membrane protein overexpression and purification in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 104 (35) : 13936-13941. Ekman, D., Bjorklund, A.K. and Elofsson, A. (2007) Quantification of the elevated rate of domain rearrangements in metazoa. J Mol Biol 372 (5) : 1337-1348. Andersson, S.A. and Lagergren, J. (2007) Motif yggdrasil: sampling sequence motifs from a tree mixture model. J Comput Biol 14 (5) : 682-697. Lundin, C., Johansson, S., Johnson, A.E., Naslund, J., von Heijne, G. and Nilsson, I. (2007) Stable insertion of Alzheimer Abeta peptide into the ER membrane strongly correlates with its length. FEBS Lett 581 (20) : 3809-3813. Bertaccini, E.J., Trudell, J.R. and Lindahl, E. (2007) Normal-Mode Analysis of the Glycine Alpha1 Receptor by Three Separate Methods. J Chem Inf Model 47 (4) : 1572-1579. Wallner, B., Larsson, P. and Elofsson, A. (2007) Pcons.net: protein structure prediction meta server. Nucleic Acids Res 35 (suppl_2) : W369-W374. Stenberg, F., von Heijne, G. and Daley, D.O. (2007) Assembly of the Cytochrome bo(3) Complex. J Mol Biol 371 (3) : 765-773. Elofsson, A. and Heijne, G. (2007) Membrane Protein Structure: Prediction versus Reality. Annu Rev Biochem 76: 125-140. Euskirchen, G.M., Rozowsky, J.S., Wei, C.L., Lee, W.H., Zhang, Z.D., Hartman, S., Emanuelsson, O., Stolc, V., Weissman, S., Gerstein, M.B., Ruan, Y. and Snyder, M. (2007) Mapping of transcription factor binding regions in mammalian cells by ChIP: Comparison of array- and sequencing-based technologies. Genome Res 17 (6) : 898-909. Gerstein, M.B., Bruce, C., Rozowsky, J.S., Zheng, D., Du, J., Korbel, J.O., Emanuelsson, O., Zhang, Z.D., Weissman, S. and Snyder, M. (2007) What is a gene, post-ENCODE? History and 4 updated definition. Genome Res 17 (6) : 669-681. von Heijne, G. (2007) Membrane proteins up for grabs. Nat Biotechnol 25 (6) : 646-647. von Heijne, G. (2007) The membrane protein universe: what's out there and why bother? J Intern Med 261 (6) : 543-557. Julenius, K. (2007) NetCGlyc 1.0: prediction of mammalian C-mannosylation sites. Glycobiology 17 (8) : 868-876. Zhang, L., Sato, Y., Hessa, T., von Heijne, G., Lee, J.K., Kodama, I., Sakaguchi, M. and Uozumi, N. (2007) Contribution of hydrophobic and electrostatic interactions to the membrane integration of the Shaker K+ channel voltage sensor domain. Proc Natl Acad Sci U S A 104 (20) : 8263-8268. Sennblad, B., Schreil, E., Berglund Sonnhammer, A.C., Lagergren, J. and Arvestad, L. (2007) primetv: a viewer for reconciled trees. BMC Bioinformatics 8: 148. Kall, L., Krogh, A. and Sonnhammer, E.L. (2007) Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server. Nucleic Acids Res 35 (suppl_2) : W429-W432. Vogt, G., Vogt, B., Chuzhanova, N., Julenius, K., Cooper, D.N. and Casanova, J.L. (2007) Gain-of-glycosylation mutations. Curr Opin Genet Dev 17 (3) : 245-251. Emanuelsson, O., Brunak, S., von Heijne, G. and Nielsen, H. (2007) Locating proteins in the cell using TargetP, SignalP and related tools. Nat Protoc 2 (4) : 953-971. von Heijne, G. (2007) Formation of Transmembrane Helices In Vivo--Is Hydrophobicity All that Matters? J Gen Physiol 129 (5) : 353-356. Kutzner, C., Van Der Spoel, D., Fechner, M., Lindahl, E., Schmitt, U.W., De Groot, B.L. and Grubmuller, H. (2007) Speeding up parallel GROMACS on high-latency networks. J Comput Chem 28 (12) : 2075-2084. Wang, H., Julenius, K., Hryhorenko, J. and Hagen, F.K. (2007) Systematic Analysis of proteoglycan modification sites in Caenorhabditis elegans by scanning mutagenesis. J Biol Chem 282 (19) : 14586-14597.
Load more

Recommended publications
  • Methodology for Predicting Semantic Annotations of Protein Sequences by Feature Extraction Derived of Statistical Contact Potentials and Continuous Wavelet Transform
    Universidad Nacional de Colombia Sede Manizales Master’s Thesis Methodology for predicting semantic annotations of protein sequences by feature extraction derived of statistical contact potentials and continuous wavelet transform Author: Supervisor: Gustavo Alonso Arango Dr. Cesar German Argoty Castellanos Dominguez A thesis submitted in fulfillment of the requirements for the degree of Master’s on Engineering - Industrial Automation in the Department of Electronic, Electric Engineering and Computation Signal Processing and Recognition Group June 2014 Universidad Nacional de Colombia Sede Manizales Tesis de Maestr´ıa Metodolog´ıapara predecir la anotaci´on sem´antica de prote´ınaspor medio de extracci´on de caracter´ısticas derivadas de potenciales de contacto y transformada wavelet continua Autor: Tutor: Gustavo Alonso Arango Dr. Cesar German Argoty Castellanos Dominguez Tesis presentada en cumplimiento a los requerimientos necesarios para obtener el grado de Maestr´ıaen Ingenier´ıaen Automatizaci´onIndustrial en el Departamento de Ingenier´ıaEl´ectrica,Electr´onicay Computaci´on Grupo de Procesamiento Digital de Senales Enero 2014 UNIVERSIDAD NACIONAL DE COLOMBIA Abstract Faculty of Engineering and Architecture Department of Electronic, Electric Engineering and Computation Master’s on Engineering - Industrial Automation Methodology for predicting semantic annotations of protein sequences by feature extraction derived of statistical contact potentials and continuous wavelet transform by Gustavo Alonso Arango Argoty In this thesis, a method to predict semantic annotations of the proteins from its primary structure is proposed. The main contribution of this thesis lies in the implementation of a novel protein feature representation, which makes use of the pairwise statistical contact potentials describing the protein interactions and geometry at the atomic level.
    [Show full text]
  • EMBO Encounters Issue43.Pdf
    WINTER 2019/2020 ISSUE 43 Nine group leaders selected Meet the first EMBO Global Investigators PAGE 6 Accelerating scientific publishing EMBO publishing costs Review Commons Making our journals’ platform announced finances public PAGE 3 PAGES 10 – 11 Welcome, Young Investigators! Contract replaces stipend Marking ten years 27 group leaders join the programme EMBO Postdoctoral Fellowships EMBO Molecular Medicine receive an update celebrates anniversary PAGES 4 – 5 PAGE 7 PAGE 13 www.embo.org TABLE OF CONTENTS EMBO NEWS EMBO news Review Commons: accelerating publishing Page 3 EMBO Molecular Medicine turns ten © Marietta Schupp, EMBL Photolab Marietta Schupp, © Page 13 Editorial MBO was founded by scientists for Introducing 27 new Young Investigators scientists. This philosophy remains at Pages 4-5 Ethe heart of our organization until today. EMBO Members are vital in the running of our Meet the first EMBO Global programmes and activities: they screen appli- Accelerating scientific publishing 17 journals on board Investigators cations, interview candidates, decide on fund- Review Commons will manage the transfer of ing, and provide strategic direction. On pages EMBO and ASAPbio announced pre-journal portable review platform the manuscript, reviews, and responses to affili- Page 6 8-9 four members describe why they chose to ate journals. A consortium of seventeen journals New members meet in Heidelberg dedicate their time to an EMBO Committee across six publishers (see box) have joined the Fellowships: from stipends to contracts Pages 14 – 15 and what they took away from the experience. n December 2019, EMBO, in partnership with decide to submit their work to a journal, it will project by committing to use the Review Commons Page 7 When EMBO was created, the focus lay ASAPbio, launched Review Commons, a multi- allow editors to make efficient editorial decisions referee reports for their independent editorial deci- specifically on fostering cross-border inter- Ipublisher partnership which aims to stream- based on existing referee comments.
    [Show full text]
  • Refining Neural Network Predictions for Helical Transmembraneproteins by Dynamic Programming
    From: ISMB-96 Proceedings. Copyright © 1996, AAAI (www.aaai.org). All rights reserved. Refining neural network predictions for helical transmembraneproteins by dynamic programming BurkhardRost 0, Rita Casadio, and Piero Fariselli EMBL,69012 Heidelberg, Germany Lab. of Biophysics, Dep. of Biology EBI, Hinxton, Cambridge CB101RQ, U.K. Univ. of Bologna, 40126 Bologna, Italy Rost @embl-heidelberg.de Casadio @kaiser.alma.unibo.it Abstract time. Currently, the gap between the number of known For transmembrane proteins experimental determina- protein sequences and protein three-dimensional (3D) tion of three-dimensional structure is problematic. structures is still increasing (Rost 1995). However, However, membraneproteins have important impact experimental structure determination is becomingmore of for molecular biology in general, and for drug design a routine (Lattman 1994). Thus, within the next decades in particular. Thus, prediction method are needed. we may know the three-dimensional (3D) structure for Here we introduce a method that started from the most proteins. Even in such an optimistic scenario, output of the profile-based neural network system experimental information is likely to remain scarce for PHDhtm(Rost, et al. 1995). Instead of choosing the integral membraneproteins. These challenge experimental neural network output unit with maximalvalue as pre- structure determination: X-ray crystallography is diction, we implemented a dynamic programming-like problematic as the hydrophobic molecules hardly refinement procedure that aimed at producing the best crystallise; and for nuclear magnetic resonance (NMR) model for all transmembranehelices compatible with spectroscopy transmembraneproteins are usually too long. the neural network output. The refined prediction was Today, 3D structure is known for only six membrane used successfully to predict transmembranetopology proteins (Rost, et al.
    [Show full text]
  • A Day in the Life of Dr K. Or How I Learned to Stop Worrying and Love Lysozyme: a Tragedy in Six Acts Gunnar Von Heijne
    Article No. jmbi.1999.2998 available online at http://www.idealibrary.com on J. Mol. Biol. (1999) 293, 367±379 A Day in the Life of Dr K. or How I Learned to Stop Worrying and Love Lysozyme: A Tragedy in Six Acts Gunnar von Heijne Department of Biochemistry About the play: In modern drama, the agonizing nature of membrane Stockholm University, S-106 91 protein work has not been adequately acknowledged. It is perhaps sig- Stockholm, Sweden ni®cant that the ®rst attempt to bring this darker aspect of human exist- ence into focus comes from a Scandinavian author, writing in the tradition of Ibsen and Strindberg but with a distinctly turn-of-the-millen- ium approach to the inner life of his characters: the despairing Dr K; the cynical Dr R with his post-modernistic life credo; the ambitious but unfeeling Dr C; the modern UÈ bermensch, Dr B., with his almost Nietzschean view of human nature. This is a play that is brutally honest, yet full of empathy for the poor souls that get caught between the Scylla of unreachable scienti®c glory and the Charybdis of helpless mediocrity. James Glib-Burdock, drama critic for The Stratford Observer. # 1999 Academic Press Keywords: membrane protein; modern tragedy The Cast Dr K., a middle-aged biochemist with a certain interest in membrane proteins. Dr R., another middle-aged biochemist with other things on his mind. Dr C., a young, hungry crystallographer. Dr B., a bioinformatics guru. Dr H., over in molecular biology. A class of medical school students. Act I Wherein Dr K.
    [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]
  • Glycoprotein Hormone Receptors in Sea Lamprey
    University of New Hampshire University of New Hampshire Scholars' Repository Doctoral Dissertations Student Scholarship Fall 2007 Glycoprotein hormone receptors in sea lamprey (Petromyzon marinus): Identification, characterization and implications for the evolution of the vertebrate hypothalamic-pituitary-gonadal/thyroid axes Mihael Freamat University of New Hampshire, Durham Follow this and additional works at: https://scholars.unh.edu/dissertation Recommended Citation Freamat, Mihael, "Glycoprotein hormone receptors in sea lamprey (Petromyzon marinus): Identification, characterization and implications for the evolution of the vertebrate hypothalamic-pituitary-gonadal/ thyroid axes" (2007). Doctoral Dissertations. 395. https://scholars.unh.edu/dissertation/395 This Dissertation is brought to you for free and open access by the Student Scholarship at University of New Hampshire Scholars' Repository. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of University of New Hampshire Scholars' Repository. For more information, please contact [email protected]. GLYCOPROTEIN HORMONE RECEPTORS IN SEA LAMPREY (PETROMYZON MARI Nil S): IDENTIFICATION, CHARACTERIZATION AND IMPLICATIONS FOR THE EVOLUTION OF THE VERTEBRATE HYPOTHALAMIC-PITUITARY-GONADAL/THYROID AXES BY MIHAEL FREAMAT B.S. University of Bucharest, 1995 DISSERTATION Submitted to the University of New Hampshire in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy In Biochemistry September, 2007 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number: 3277139 INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted.
    [Show full text]
  • Downloaded from Genbank, with Accession Numbers Found in Table 1
    bioRxiv preprint doi: https://doi.org/10.1101/030619; this version posted November 4, 2015. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Common and phylogenetically widespread coding for peptides by bacterial small RNAs Robin C. Friedmana,b, Stefan Kalkhofc,d, Olivia Doppelt-Azerouale, Stephan Muellerc, Martina Chovancov´ac, Martin von Bergenc,f,g, Benno Schwikowskia a Systems Biology Laboratory, Institut Pasteur, Paris, France b Molecular Microbial Pathogenesis Unit, Institut Pasteur, Paris, France c Department of Proteomics, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany d Current Address: Department of Bioanalytics, University of Applied Sciences and Arts of Coburg, Coburg, Germany e Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, France f Department of Metabolomics, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany g Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark November 4, 2015 Abstract While eukaryotic noncoding RNAs have recently received intense scrutiny, it is becoming clear that bacterial transcription is at least as pervasive. Bacterial small RNAs and antisense RNAs (sRNAs) are often assumed to be noncoding, due to their lack of long open reading frames (ORFs). However, there are numerous examples of sRNAs encoding for small proteins, whether or not they also have a regulatory role at the RNA level. Here, we apply flexible machine learning techniques based on sequence features and comparative genomics to quantify the prevalence of sRNA ORFs under natural selection to maintain protein-coding function in phylogenetically diverse bacteria.
    [Show full text]
  • Topology Prediction of Α-Helical Transmembrane Proteins – Christoph Peters
    Topology Prediction of a-Helical Transmembrane Proteins – Christoph Peters Topology Prediction of a-Helical Transmembrane Proteins Christoph Peters Abstract Membrane proteins fulfil a number of tasks in cells, including signalling, cell-cell in- teraction, and the transportation of molecules. The prominence of these tasks makes membrane proteins an important target for clinical drugs. Because of the decreas- ing price of sequencing, the number of sequences known is increasing at such a rate that manual annotations cannot compete. Here, topology prediction is a way to pro- vide additional information. It predicts the location and number of transmembrane helices in the protein and the orientation inside the membrane. An important factor to detect transmembrane helices is their hydrophobicity, which can be calculated using dedicated scales. In the first paper, we studied the difference between several hy- drophobicity scales and evaluated their performance. We show that while they appear to be similar, their performance for topology prediction differs significantly. The bet- ter performing scales appear to measure the probability of amino acids being within a transmembrane helix, instead of just being located in a hydrophobic environment. Around 20% of the transmembrane helices are too hydrophilic to explain their insertion with hydrophobicity alone. These are referred to as marginally hydrophobic helices. In the second paper, we studied three of these helices experimentally and performed an analysis on membrane proteins. The experiments show that for all three helices positive charges on the N-terminal side of the subsequent helix are important to insert, but only two need the subsequent helix. Additionally, the analysis shows that not only the N-terminal helices are more hydrophobic, but also the C-terminal transmembrane helices.
    [Show full text]
  • Approaches to Efficient Multiple Sequence Alignment And
    Approaches to Efficient Multiple Sequence Alignment and Protein Search Adrienn Szab´o Supervisor: Istv´anMikl´os E¨otv¨os Lor´and University, Budapest Faculty of Informatics PhD School of Computer Science Erzs´ebet Csuhaj-Varj´u,D.Sc. PhD Program of ”Basics and methodology of informatics” J´anosDemetrovics, D.Sc. A dissertation submitted for the degree of PhilosophiæDoctor (PhD) 2016 ii Acknowledgements Firstly, I would like to thank the extensive help and guidance of my supervisors, Istv´anMikl´os and Andr´asA. Bencz´ur . I would also like to express my gratitude to M´aty´asBachorecz and N´ora Juh´asz , who helped tremendously in developing, coding and testing the software packages of Chapter 5. Lastly, I list here all my friends and colleagues at MTA SZTAKI, who contributed to the final version of this thesis by pointing out several typos and mistakes: Akos´ Csaba, D´avidBalamb´er, Tam´as Kiss, J´uliaPap, D´avidSikl´osi,P´eterSzab´o. ii Contents 1 Introduction 1 1.1 Datamining................................ 2 1.2 Bioinformatics .............................. 3 2 Sequence alignment methods 5 2.1 Theory and practice of sequence alignment . 6 2.2 Cornercuttingmethods. 32 2.3 Progressivealignment .......................... 35 2.4 SoftwaretoolsforMSA ......................... 38 2.5 Handlingalignmentuncertainty . 41 2.6 Introductiontoproteinsearchmethods . 43 3 Reticular Alignment 47 3.1 Introduction................................ 47 3.2 Methods .................................. 50 3.3 Resultsanddiscussion.......................... 59 3.4 Implementation details and authors’ contributions . ...... 65 4 Efficient representation of uncertainty in MSA 69 4.1 Introduction................................ 69 4.2 Methods .................................. 70 iii CONTENTS 4.3 Implementation details and measurements . 74 4.4 Resultsandconclusions ......................... 79 5 Protein Search 83 5.1 Background ...............................
    [Show full text]
  • Structure and Topology Around the Cleavage Site Regulate Post
    RESEARCH ARTICLE Structure and topology around the cleavage site regulate post-translational cleavage of the HIV-1 gp160 signal peptide Erik Lee Snapp1†, Nicholas McCaul2†, Matthias Quandte2‡, Zuzana Cabartova3, Ilja Bontjer4, Carolina Ka¨ llgren5,6, IngMarie Nilsson5,6, Aafke Land2§, Gunnar von Heijne5,6, Rogier W Sanders4, Ineke Braakman2* 1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States; 2Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands; 3National Institute of Public Health, National Reference Laboratory for Viral Hepatitis, Prague, Czech Republic; 4Department of Medical Microbiology, Laboratory of Experimental Virology, Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, Netherlands; 5Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden; 6Science for Life Laboratory, Stockholm University, Solna, Sweden *For correspondence: Abstract Like all other secretory proteins, the HIV-1 envelope glycoprotein gp160 is targeted to [email protected] the endoplasmic reticulum (ER) by its signal peptide during synthesis. Proper gp160 folding in the †These authors contributed ER requires core glycosylation, disulfide-bond formation and proline isomerization. Signal-peptide equally to this work cleavage occurs only late after gp160 chain termination and is dependent on folding of the soluble Present address: ‡dr heinekamp subunit gp120 to a near-native conformation. We here detail the mechanism by which co- Benelux BV, Riethoven, translational signal-peptide cleavage is prevented. Conserved residues from the signal peptide and Netherlands; §Hogeschool residues downstream of the canonical cleavage site form an extended alpha-helix in the ER Utrecht, Institute of Life membrane, which covers the cleavage site, thus preventing cleavage.
    [Show full text]
  • CV Burkhard Rost
    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 Photo: © Eckert & Heddergott, TUM Web www.rostlab.org Fax +49-89-289-19-414 Document: CV Burkhard Rost TU München Affiliation: Columbia University TOC: • Tabulated curriculum vitae • Grants • List of publications Highlights by numbers: • 186 invited talks in 29 countries (incl. TedX) • 250 publications (187 peer-review, 168 first/last author) • Google Scholar 2016/01: 30,502 citations, h-index=80, i10=179 • PredictProtein 1st Internet server in mol. biol. (since 1992) • 8 years ISCB President (International Society for Computational Biology) • 143 trained (29% female, 50% foreigners from 32 nations on 6 continents) 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]
  • Experimentally Based Topology Models for E. Coli Inner Membrane Proteins
    Experimentally based topology models for E. coli inner membrane proteins MIKAELA RAPP,1 DAVID DREW,1 DANIEL O. DALEY,1 JOHAN NILSSON,2,3 1,2 1,2 1 TIAGO CARVALHO, KARIN MELÉN, JAN-WILLEM DE GIER, AND GUNNAR VON HEIJNE1,2 1Department of Biochemistry and Biophysics, and 2Stockholm Bioinformatics Center, Stockholm University, Stockholm, Sweden 3Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (RECEIVED December 8, 2003; FINAL REVISION January 9, 2004; ACCEPTED January 9, 2004) Abstract Membrane protein topology predictions can be markedly improved by the inclusion of even very limited experimental information. We have recently introduced an approach for the production of reliable topology models based on a combination of experimental determination of the location (cytoplasmic or periplasmic) of a protein’s C terminus and topology prediction. Here, we show that determination of the location of a protein’s C terminus, rather than some internal loop, is the best strategy for large-scale topology mapping studies. We further report experimentally based topology models for 31 Escherichia coli inner membrane proteins, using methodology suitable for genome-scale studies. Keywords: membrane proteins; topology; prediction; bioinformatics; fusion protein; PhoA; green fluores- cent protein; GFP Supplemental material: see www.proteinscience.org The topology of an integral membrane protein—that is, a ogy prediction methods can be substantially improved by specification of the membrane-spanning segments of the the inclusion of limited experimental information such as polypeptide chain and their in/out orientation relative to the the location of the N- or C-terminal end of the protein membrane—is a basic characteristic that helps guide experi- relative to the membrane (Drew et al.
    [Show full text]