DOCSLIB.ORG

Sequence Motifs, Correlations and Structural Mapping of Evolutionary

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Sequence Motifs, Correlations and Structural Mapping of Evolutionary Talk overview • Sequence profiles – position specific scoring matrix • Psi-blast. Automated way to create and use sequence Sequence motifs, correlations profiles in similarity searches and structural mapping of • Sequence patterns and sequence logos evolutionary data • Bioinformatic tools which employ sequence profiles: PFAM BLOCKS PROSITE PRINTS InterPro • Correlated Mutations and structural insight • Mapping sequence data on structures: March 2011 Eran Eyal Conservations Correlations PSSM – position specific scoring matrix • A position-specific scoring matrix (PSSM) is a commonly used representation of motifs (patterns) in biological sequences • PSSM enables us to represent multiple sequence alignments as mathematical entities which we can work with. • PSSMs enables the scoring of multiple alignments with sequences, or other PSSMs. PSSM – position specific scoring matrix Assuming a string S of length n S = s1s2s3...sn If we want to score this string against our PSSM of length n (with n lines): n alignment _ score = m ∑ s j , j j=1 where m is the PSSM matrix and sj are the string elements. PSSM can also be incorporated to both dynamic programming algorithms and heuristic algorithms (like Psi-Blast). Sequence space PSI-BLAST • For a query sequence use Blast to find matching sequences. • Construct a multiple sequence alignment from the hits to find the common regions (consensus). • Use the “consensus” to search again the database, and get a new set of matching sequences • Repeat the process ! Sequence space Position-Specific-Iterated-BLAST • Intuition – substitution matrices should be specific to sites and not global. – Example: penalize alanine→glycine more in a helix •Idea – Use BLAST with high stringency to get a set of closely related sequences. – Align those sequences to create a new substitution matrix for each position. – Then use that matrix to find additional sequences. Position-Specific-Iterated-BLAST PSI-BLAST Principle • Cycling/iterative method • First, a standard blastp is performed – Gives increased sensitivity for detecting distantly related • The highest scoring hits are used to generate a multiple proteins alignment – Can give insight into functional relationships – Very refined statistical methods •A PSSM is generated from the multiple alignment. • Fast and simple • Another similarity search is performed, this time using the new PSSM • Repeat previous steps until convergence (no new sequences appear after iteration) Sequence space Example: Aminoacyl tRNA Synthetases • Each is very different – Aminoacyl tRNA Synthetases are very different: size, multimers, etc… – But all bind to their own tRNAs and amino acids with high specificity. • TrpRS and TyrRS share only 13% sequence identity – Yet the structures of TrpTRS and TyrTRS are similar –Structure Ù Function relationship (See ellipsoid slide from previous lecture…) • Given structural similarities, we would expect to find sequence similarity… Same SCOP family based • However, blastp of E.coli TyrRS against bacterial on catalytic domain sequences in SwissProt does NOT show similarity with TrpRS at e-value cutoff of 10 Overall structure similarity noted No TrpRS! After a few iterations… TrpRS Similarity to TyrRS! PSI-BLAST Using PSI-BLAST • PSI-BLAST available from BLAST web sites – Be sure to inspect and think about the results • Query form just like for blastp included in the PSSM build – BUT: one extra formatting option must be used – include/exclude sequences on basis of biological knowledge: you are in the driving seat! – A special e-value cutoff used to determine which – PSI-BLAST performance varies according to alignments will be used for PSSM build. choice of matrix, filter, statistics and nature of – PSI-BLAST also available from the stand alone data just like any other alignment tool. versions of BLAST. Why (not) PSI-BLAST Query • If the sequences used to construct the Position Specific Scoring Matrices (PSSMs) are true homologous, the sensitivity at a given specificity improves significantly. • However, if non-homologous sequences are included in the PSSMs, they are “corrupted.” Then they pull in false non-homologous sequences and will amplify the errors in the next rounds. Does the query really • If all hits in the first rounds are highly similar, then the have a relationship with the results? prediction power of the new PSSM will not be significantly better than of the original substitution matrix PSI-BLAST PSI-BLAST caveat on the command line • Increased ability to find distant homologues • As with simple BLAST searches, using PSI-BLAST on • Cost of additional required care to prevent non- the command line gives the user more power homologous sequences from being included in the • Opens up additional options, e.g. PSSM calculation – PSI-BLASTing over nucleotide databases – When in doubt, leave it out! – Examine sequences with moderate similarity carefully. – automating number of iterations • Be particularly cautious about matches to sequences – trying out lots of different settings in parallel with highly biased amino acid content – inputting multiple sequences – Low complexity regions, transmembrane regions and coiled-coil regions often display significant similarity without homology – Screen them out of your query sequences! PFAM – Database of Protein families represented by HMM The Pfam database is a large collection of protein domain families. Each • The HMM are generated using the HMMER3 program, which is a new and family is represented by multiple sequence alignments and hidden efficient HMM builder. Markov models (HMMs). • There is a new option to search single DNA sequences against the library of There are two levels of quality to Pfam families: Pfam-A and Pfam-B. Pfam HMMs For each Pfam-A family Pfam builds a single curated profile hidden Markov model (HMM) from a seed alignment (a small set of • HMM models can be downloaded, as well as the multiple alignments of the representative members of the family). Pfam-B families have no seed and full alignments used to create the models. associated annotation or literature reference and are of much lower quality than Pfam-A families. Release 24.0 has 11912 families For each Pfam accession there is a family page, which can be accessed in several ways. Prosite http://www.expasy.org/prosite • PROSITE is a method of determining what is the function of uncharacterized proteins translated from genomic or cDNA sequences. It consists of a database of biologically significant sites and patterns. One can rapidly and reliably identify to which known family of protein (if any) the new sequence belongs. • In some cases the sequence of an unknown protein is too distantly related to any protein of known structure to detect its resemblance by overall sequence alignment, but it can be identified by the occurrence in its sequence of a particular cluster of residues which is variously known as a pattern, motif, signature, or fingerprint. What is a sequence pattern A Pattern in our context is a Protein WORD conserved in many sequences: PVAILL A pattern lets you identify a protein family http://expasy.org/prosite/ Prosite patterns can describe complex signatures [RK]-x-[ST] This reads as follows: “an Arginine or a Lysine, followed by one random residue, followed by a Serine or a Threonine” C-[DES]-x-C-x(3)-I-x(3)-R-x(4)-P-x(4)-C-x(2)-C Is a signature for Zn finger proteins which bind DNA Using PrositeScan http://expasy.org/tools/scanprosite/ MALRAGLVLG FHTLMTLLSP QEAGATKADH MGSYGPAFYQ SYGASGQFTH EFDEEQLFSV DLKKSEAVWR LPEFGDFARF DPQGGLAGIA AIKAHLDILV ERSNRSRAIN VPPRVTVLPK SRVELGQPNI LICIVDNIFP PVINITWLRN GQTVTEGVAQ TSFYSQPDHL FRKFHYLPFV Using PrositeScan Using PROSITE-Scan: Structure Prints Direct PRINTS access: http://www.bioinf.manchester.ac.uk/dbbrowser/PRINTS/index.php By accession number By PRINTS code • PRINTS is a compendium of protein fingerprints which are conserved By database code motifs used to characterize a protein family. By text • Release 41.1 of PRINTS contains 2050 entries, encoding 12,121 individual By sequence motifs. By title • Two types of fingerprint are represented in the database: simple or By number of motifs By author composite. simple fingerprints are essentially single-motifs; while composite By query language fingerprints encode multiple motifs. • Most entries are of the latter type because discrimination power is greater for multi-component searches, and results are easier to interpret. Sequence logos • A sequence logo is a graphical representation of aligned sequences where at each position the size of each residue is proportional to its frequency in that position and the total height of all the residues in the position is proportional to the conservation (information content) of the position InterPro Blocks http://www.ebi.ac.uk/interpro/ • InterPro is an integrated database of predictive protein "signatures" used for the classification and automatic annotation of proteins and genomes. • Blocks are multiply aligned ungapped segments corresponding to the • It facilitates prediction for the occurrence of functional domains, repeats and most highly conserved regions of proteins. important sites. • The blocks for the Blocks Database are made automatically by • InterPro combines a number of databases (referred to as member databases) looking for the most highly conserved regions in groups of proteins. that use different methodologies to derive protein signatures. By uniting the • Blocks is not updated any more. The last version of database (14.3) member databases, InterPro capitalises
Load more

Recommended publications
  • Optimal Matching Distances Between Categorical Sequences: Distortion and Inferences by Permutation Juan P
    St. Cloud State University theRepository at St. Cloud State Culminating Projects in Applied Statistics Department of Mathematics and Statistics 12-2013 Optimal Matching Distances between Categorical Sequences: Distortion and Inferences by Permutation Juan P. Zuluaga Follow this and additional works at: https://repository.stcloudstate.edu/stat_etds Part of the Applied Statistics Commons Recommended Citation Zuluaga, Juan P., "Optimal Matching Distances between Categorical Sequences: Distortion and Inferences by Permutation" (2013). Culminating Projects in Applied Statistics. 8. https://repository.stcloudstate.edu/stat_etds/8 This Thesis is brought to you for free and open access by the Department of Mathematics and Statistics at theRepository at St. Cloud State. It has been accepted for inclusion in Culminating Projects in Applied Statistics by an authorized administrator of theRepository at St. Cloud State. For more information, please contact [email protected]. OPTIMAL MATCHING DISTANCES BETWEEN CATEGORICAL SEQUENCES: DISTORTION AND INFERENCES BY PERMUTATION by Juan P. Zuluaga B.A. Universidad de los Andes, Colombia, 1995 A Thesis Submitted to the Graduate Faculty of St. Cloud State University in Partial Fulfillment of the Requirements for the Degree Master of Science St. Cloud, Minnesota December, 2013 This thesis submitted by Juan P. Zuluaga in partial fulfillment of the requirements for the Degree of Master of Science at St. Cloud State University is hereby approved by the final evaluation committee. Chairperson Dean School of Graduate Studies OPTIMAL MATCHING DISTANCES BETWEEN CATEGORICAL SEQUENCES: DISTORTION AND INFERENCES BY PERMUTATION Juan P. Zuluaga Sequence data (an ordered set of categorical states) is a very common type of data in Social Sciences, Genetics and Computational Linguistics.
    [Show full text]
  • The ELIXIR Core Data Resources: ​Fundamental Infrastructure for The
    Supplementary Data: The ELIXIR Core Data Resources: fundamental infrastructure ​ for the life sciences The “Supporting Material” referred to within this Supplementary Data can be found in the Supporting.Material.CDR.infrastructure file, DOI: 10.5281/zenodo.2625247 (https://zenodo.org/record/2625247). ​ ​ Figure 1. Scale of the Core Data Resources Table S1. Data from which Figure 1 is derived: Year 2013 2014 2015 2016 2017 Data entries 765881651 997794559 1726529931 1853429002 2715599247 Monthly user/IP addresses 1700660 2109586 2413724 2502617 2867265 FTEs 270 292.65 295.65 289.7 311.2 Figure 1 includes data from the following Core Data Resources: ArrayExpress, BRENDA, CATH, ChEBI, ChEMBL, EGA, ENA, Ensembl, Ensembl Genomes, EuropePMC, HPA, IntAct /MINT , InterPro, PDBe, PRIDE, SILVA, STRING, UniProt ● Note that Ensembl’s compute infrastructure physically relocated in 2016, so “Users/IP address” data are not available for that year. In this case, the 2015 numbers were rolled forward to 2016. ● Note that STRING makes only minor releases in 2014 and 2016, in that the interactions are re-computed, but the number of “Data entries” remains unchanged. The major releases that change the number of “Data entries” happened in 2013 and 2015. So, for “Data entries” , the number for 2013 was rolled forward to 2014, and the number for 2015 was rolled forward to 2016. The ELIXIR Core Data Resources: fundamental infrastructure for the life sciences ​ 1 Figure 2: Usage of Core Data Resources in research The following steps were taken: 1. API calls were run on open access full text articles in Europe PMC to identify articles that ​ ​ mention Core Data Resource by name or include specific data record accession numbers.
    [Show full text]
  • Dual Proteome-Scale Networks Reveal Cell-Specific Remodeling of the Human Interactome
    bioRxiv preprint doi: https://doi.org/10.1101/2020.01.19.905109; this version posted January 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Dual Proteome-scale Networks Reveal Cell-specific Remodeling of the Human Interactome Edward L. Huttlin1*, Raphael J. Bruckner1,3, Jose Navarrete-Perea1, Joe R. Cannon1,4, Kurt Baltier1,5, Fana Gebreab1, Melanie P. Gygi1, Alexandra Thornock1, Gabriela Zarraga1,6, Stanley Tam1,7, John Szpyt1, Alexandra Panov1, Hannah Parzen1,8, Sipei Fu1, Arvene Golbazi1, Eila Maenpaa1, Keegan Stricker1, Sanjukta Guha Thakurta1, Ramin Rad1, Joshua Pan2, David P. Nusinow1, Joao A. Paulo1, Devin K. Schweppe1, Laura Pontano Vaites1, J. Wade Harper1*, Steven P. Gygi1*# 1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA. 2Broad Institute, Cambridge, MA, 02142, USA. 3Present address: ICCB-Longwood Screening Facility, Harvard Medical School, Boston, MA, 02115, USA. 4Present address: Merck, West Point, PA, 19486, USA. 5Present address: IQ Proteomics, Cambridge, MA, 02139, USA. 6Present address: Vor Biopharma, Cambridge, MA, 02142, USA. 7Present address: Rubius Therapeutics, Cambridge, MA, 02139, USA. 8Present address: RPS North America, South Kingstown, RI, 02879, USA. *Correspondence: [email protected] (E.L.H.), [email protected] (J.W.H.), [email protected] (S.P.G.) #Lead Contact: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.01.19.905109; this version posted January 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]
  • Computational Biology Lecture 8: Substitution Matrices Saad Mneimneh
    Computational Biology Lecture 8: Substitution matrices Saad Mneimneh As we have introduced last time, simple scoring schemes like +1 for a match, -1 for a mismatch and -2 for a gap are not justifiable biologically, especially for amino acid sequences (proteins). Instead, more elaborated scoring functions are used. These scores are usually obtained as a result of analyzing chemical properties and statistical data for amino acids and DNA sequences. For example, it is known that same size amino acids are more likely to be substituted by one another. Similarly, amino acids with same affinity to water are likely to serve the same purpose in some cases. On the other hand, some mutations are not acceptable (may lead to demise of the organism). PAM and BLOSUM matrices are amongst results of such analysis. We will see the techniques through which PAM and BLOSUM matrices are obtained. Substritution matrices Chemical properties of amino acids govern how the amino acids substitue one another. In principle, a substritution matrix s, where sij is used to score aligning character i with character j, should reflect the probability of two characters substituing one another. The question is how to build such a probability matrix that closely maps reality? Different strategies result in different matrices but the central idea is the same. If we go back to the concept of a high scoring segment pair, theory tells us that the alignment (ungapped) given by such a segment is governed by a limiting distribution such that ¸sij qij = pipje where: ² s is the subsitution matrix used ² qij is the probability of observing character i aligned with character j ² pi is the probability of occurrence of character i Therefore, 1 qij sij = ln ¸ pipj This formula for sij suggests a way to constrcut the matrix s.
    [Show full text]
  • Development of Novel Classical and Quantum Information Theory Based Methods for the Detection of Compensatory Mutations in Msas
    Development of novel Classical and Quantum Information Theory Based Methods for the Detection of Compensatory Mutations in MSAs Dissertation zur Erlangung des mathematisch-naturwissenschaftlichen Doktorgrades ”Doctor rerum naturalium” der Georg-August-Universität Göttingen im Promotionsprogramm PCS der Georg-August University School of Science (GAUSS) vorgelegt von Mehmet Gültas aus Kirikkale-Türkei Göttingen, 2013 Betreuungsausschuss Professor Dr. Stephan Waack, Institut für Informatik, Georg-August-Universität Göttingen. Professor Dr. Carsten Damm, Institut für Informatik, Georg-August-Universität Göttingen. Professor Dr. Edgar Wingender, Institut für Bioinformatik, Universitätsmedizin, Georg-August-Universität Göttingen. Mitglieder der Prüfungskommission Referent: Prof. Dr. Stephan Waack, Institut für Informatik, Georg-August-Universität Göttingen. Korreferent: Prof. Dr. Carsten Damm, Institut für Informatik, Georg-August-Universität Göttingen. Korreferent: Prof. Dr. Mario Stanke, Institut für Mathematik und Informatik, Ernst Moritz Arndt Universität Greifswald Weitere Mitglieder der Prüfungskommission Prof. Dr. Edgar Wingender, Institut für Bioinformatik, Universitätsmedizin, Georg-August-Universität Göttingen. Prof. Dr. Burkhard Morgenstern, Institut für Mikrobiologie und Genetik, Abteilung für Bioinformatik, Georg-August- Universität Göttingen. Prof. Dr. Dieter Hogrefe, Institut für Informatik, Georg-August-Universität Göttingen. Prof. Dr. Wolfgang May, Institut für Informatik, Georg-August-Universität Göttingen. Tag der mündlichen
    [Show full text]
  • Sequence Motifs, Information Content, and Sequence Logos Morten
    Sequence motifs, information content, and sequence logos Morten Nielsen, CBS, Depart of Systems Biology, DTU Objectives • Visualization of binding motifs – Construction of sequence logos • Understand the concepts of weight matrix construction – One of the most important methods of bioinformatics • How to deal with data redundancy • How to deal with low counts Outline • Pattern recognition • Weight matrix – Regular expressions construction and probabilities – Sequence weighting • Information content – Low (pseudo) counts • Examples from the real – Sequence logos world • Multiple alignment and • Sequence profiles sequence motifs Binding Motif. MHC class I with peptide Anchor positions Sequence information SLLPAIVEL YLLPAIVHI TLWVDPYEV GLVPFLVSV KLLEPVLLL LLDVPTAAV LLDVPTAAV LLDVPTAAV LLDVPTAAV VLFRGGPRG MVDGTLLLL YMNGTMSQV MLLSVPLLL SLLGLLVEV ALLPPINIL TLIKIQHTL HLIDYLVTS ILAPPVVKL ALFPQLVIL GILGFVFTL STNRQSGRQ GLDVLTAKV RILGAVAKV QVCERIPTI ILFGHENRV ILMEHIHKL ILDQKINEV SLAGGIIGV LLIENVASL FLLWATAEA SLPDFGISY KKREEAPSL LERPGGNEI ALSNLEVKL ALNELLQHV DLERKVESL FLGENISNF ALSDHHIYL GLSEFTEYL STAPPAHGV PLDGEYFTL GVLVGVALI RTLDKVLEV HLSTAFARV RLDSYVRSL YMNGTMSQV GILGFVFTL ILKEPVHGV ILGFVFTLT LLFGYPVYV GLSPTVWLS WLSLLVPFV FLPSDFFPS CLGGLLTMV FIAGNSAYE KLGEFYNQM KLVALGINA DLMGYIPLV RLVTLKDIV MLLAVLYCL AAGIGILTV YLEPGPVTA LLDGTATLR ITDQVPFSV KTWGQYWQV TITDQVPFS AFHHVAREL YLNKIQNSL MMRKLAILS AIMDKNIIL IMDKNIILK SMVGNWAKV SLLAPGAKQ KIFGSLAFL ELVSEFSRM KLTPLCVTL VLYRYGSFS YIGEVLVSV CINGVCWTV VMNILLQYV ILTVILGVL KVLEYVIKV FLWGPRALV GLSRYVARL FLLTRILTI
    [Show full text]
  • The Biogrid Interaction Database
    D470–D478 Nucleic Acids Research, 2015, Vol. 43, Database issue Published online 26 November 2014 doi: 10.1093/nar/gku1204 The BioGRID interaction database: 2015 update Andrew Chatr-aryamontri1, Bobby-Joe Breitkreutz2, Rose Oughtred3, Lorrie Boucher2, Sven Heinicke3, Daici Chen1, Chris Stark2, Ashton Breitkreutz2, Nadine Kolas2, Lara O’Donnell2, Teresa Reguly2, Julie Nixon4, Lindsay Ramage4, Andrew Winter4, Adnane Sellam5, Christie Chang3, Jodi Hirschman3, Chandra Theesfeld3, Jennifer Rust3, Michael S. Livstone3, Kara Dolinski3 and Mike Tyers1,2,4,* 1Institute for Research in Immunology and Cancer, Universite´ de Montreal,´ Montreal,´ Quebec H3C 3J7, Canada, 2The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada, 3Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA, 4School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, UK and 5Centre Hospitalier de l’UniversiteLaval´ (CHUL), Quebec,´ Quebec´ G1V 4G2, Canada Received September 26, 2014; Revised November 4, 2014; Accepted November 5, 2014 ABSTRACT semi-automated text-mining approaches, and to en- hance curation quality control. The Biological General Repository for Interaction Datasets (BioGRID: http://thebiogrid.org) is an open access database that houses genetic and protein in- INTRODUCTION teractions curated from the primary biomedical lit- Massive increases in high-throughput DNA sequencing erature for all major model organism species and technologies (1) have enabled an unprecedented level of humans. As of September 2014, the BioGRID con- genome annotation for many hundreds of species (2–6), tains 749 912 interactions as drawn from 43 149 pub- which has led to tremendous progress in the understand- lications that represent 30 model organisms.
    [Show full text]
  • Seq2logo: a Method for Construction and Visualization of Amino Acid Binding Motifs and Sequence Profiles Including Sequence Weig
    Downloaded from orbit.dtu.dk on: Dec 20, 2017 Seq2Logo: a method for construction and visualization of amino acid binding motifs and sequence profiles including sequence weighting, pseudo counts and two-sided representation of amino acid enrichment and depletion Thomsen, Martin Christen Frølund; Nielsen, Morten Published in: Nucleic Acids Research Link to article, DOI: 10.1093/nar/gks469 Publication date: 2012 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Thomsen, M. C. F., & Nielsen, M. (2012). Seq2Logo: a method for construction and visualization of amino acid binding motifs and sequence profiles including sequence weighting, pseudo counts and two-sided representation of amino acid enrichment and depletion. Nucleic Acids Research, 40(W1), W281-W287. DOI: 10.1093/nar/gks469 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Published online 25 May 2012 Nucleic Acids Research, 2012, Vol.
    [Show full text]
  • The Interpro Database, an Integrated Documentation Resource for Protein
    The InterPro database, an integrated documentation resource for protein families, domains and functional sites R Apweiler, T K Attwood, A Bairoch, A Bateman, E Birney, M Biswas, P Bucher, L Cerutti, F Corpet, M D Croning, et al. To cite this version: R Apweiler, T K Attwood, A Bairoch, A Bateman, E Birney, et al.. The InterPro database, an integrated documentation resource for protein families, domains and functional sites. Nucleic Acids Research, Oxford University Press, 2001, 29 (1), pp.37-40. 10.1093/nar/29.1.37. hal-01213150 HAL Id: hal-01213150 https://hal.archives-ouvertes.fr/hal-01213150 Submitted on 7 Oct 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. © 2001 Oxford University Press Nucleic Acids Research, 2001, Vol. 29, No. 1 37–40 The InterPro database, an integrated documentation resource for protein families, domains and functional sites R. Apweiler1,*, T. K. Attwood2,A.Bairoch3, A. Bateman4,E.Birney1, M. Biswas1, P. Bucher5, L. Cerutti4,F.Corpet6, M. D. R. Croning1,2, R. Durbin4,L.Falquet5,W.Fleischmann1, J. Gouzy6,H.Hermjakob1,N.Hulo3, I. Jonassen7,D.Kahn6,A.Kanapin1, Y. Karavidopoulou1, R.
    [Show full text]
  • 3D Representations of Amino Acids—Applications to Protein Sequence Comparison and Classification
    Computational and Structural Biotechnology Journal 11 (2014) 47–58 Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/csbj 3D representations of amino acids—applications to protein sequence comparison and classification Jie Li a, Patrice Koehl b,⁎ a Genome Center, University of California, Davis, 451 Health Sciences Drive, Davis, CA 95616, United States b Department of Computer Science and Genome Center, University of California, Davis, One Shields Ave, Davis, CA 95616, United States article info abstract Available online 6 September 2014 The amino acid sequence of a protein is the key to understanding its structure and ultimately its function in the cell. This paper addresses the fundamental issue of encoding amino acids in ways that the representation of such Keywords: a protein sequence facilitates the decoding of its information content. We show that a feature-based representa- Protein sequences tion in a three-dimensional (3D) space derived from amino acid substitution matrices provides an adequate Substitution matrices representation that can be used for direct comparison of protein sequences based on geometry. We measure Protein sequence classification the performance of such a representation in the context of the protein structural fold prediction problem. Fold recognition We compare the results of classifying different sets of proteins belonging to distinct structural folds against classifications of the same proteins obtained from sequence alone or directly from structural information. We find that sequence alone performs poorly as a structure classifier.Weshowincontrastthattheuseofthe three dimensional representation of the sequences significantly improves the classification accuracy. We conclude with a discussion of the current limitations of such a representation and with a description of potential improvements.
    [Show full text]
  • Multiple Sequence Alignment
    ELB18S Entry Level Bioinformatics 05-09 November 2018 (Second 2018 run of this Course) Basic Bioinformatics Sessions Practical 6: Multiple Sequence Alignment Sunday 4 November 2018 Practical 6: Multiple Sequence Alignment Sunday 4 November 2018 Multiple Sequence Alignment Here we will look at some software tools to align some protein sequences. Before we can do that, we need some sequences to align. I propose we try all the human homeobox domains from the well annotated section of UniprotKB. Getting the sequences is a trifle clumsy, so concentrate now! There used to be a much easier way, but that was made redundant by foolish people intent on making the future ever more tricky!! So, begin by going to the home of Uniprot: http://www.uniprot.org/ Choose the option of the button. First specify that you are only interested in Human proteins. To do this, set the first field to Organism [OS] and Term to Human [9606]. Set the second field selector to Reviewed and the corresponding Term to Reviewed (that is, only SwissProt entries). If required, Click on the button to request a further field selection option. Set the new field to Function. Set the type of Function to DNA binding. Set the Term selection to Homeobox. From previous investigations, you should be aware that a Homeobox domain is generally 60 amino acids in length. To avoid partial and/or really weird Homeobox proteins, set the Length range settings to recognise only homeoboxs between 50 and 70 amino acids long. Leave the Evidence box as Any assertion method, one does not wish to be too fussy! Address the button with authority to get the search going.
    [Show full text]
  • Interpreting a Sequence Logo When Initiating Translation, Ribosomes Bind to an Mrna at a Ribosome Binding Site Upstream of the AUG Start Codon
    Interpreting a Sequence Logo When initiating translation, ribosomes bind to an mRNA at a ribosome binding site upstream of the AUG start codon. Because mRNAs from different genes all bind to a ribosome, the genes encoding these mRNAs are likely to have a similar base sequence where the ribosomes bind. Therefore, candidate ribosome binding sites on mRNA can be identified by comparing DNA sequences (and thus the mRNA sequences) of several genes in a species, searching the region upstream of the start codon for shared (conserved) base sequences. The DNA sequences of 149 genes from the E. coli genome were aligned with the aim to identify similar base sequences as potential ribosome binding sites. Rather than presenting the data as a series of 149 sequences aligned in a column (a sequence alignment), the researchers used a sequence logo. The potential ribosome binding regions from 10 E. coli genes are shown in the sequence alignment in Figure 1. The sequence logo derived from the aligned sequences is shown in Figure 2. Note that the DNA shown is the nontemplate (coding) strand, which is how DNA sequences are typically presented. Figure 1 Sequence alignment for 10 E. coli genes. Figure 2 Sequence logo derived from sequence alignment 1) In the sequence logo, the horizontal axis shows the primary sequence of the DNA by nucleotide position. Letters for each base are stacked on top of each other according to their relative frequency at that position among the aligned sequences, with the most common base as the largest letter at the top of the stack.
    [Show full text]