Lecture 7: Sequence Motif Discovery
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DNA Sequencing and Sorting: Identifying Genetic Variations
BioMath DNA Sequencing and Sorting: Identifying Genetic Variations Student Edition Funded by the National Science Foundation, Proposal No. ESI-06-28091 This material was prepared with the support of the National Science Foundation. However, any opinions, findings, conclusions, and/or recommendations herein are those of the authors and do not necessarily reflect the views of the NSF. At the time of publishing, all included URLs were checked and active. We make every effort to make sure all links stay active, but we cannot make any guaranties that they will remain so. If you find a URL that is inactive, please inform us at [email protected]. DIMACS Published by COMAP, Inc. in conjunction with DIMACS, Rutgers University. ©2015 COMAP, Inc. Printed in the U.S.A. COMAP, Inc. 175 Middlesex Turnpike, Suite 3B Bedford, MA 01730 www.comap.com ISBN: 1 933223 71 5 Front Cover Photograph: EPA GULF BREEZE LABORATORY, PATHO-BIOLOGY LAB. LINDA SHARP ASSISTANT This work is in the public domain in the United States because it is a work prepared by an officer or employee of the United States Government as part of that person’s official duties. DNA Sequencing and Sorting: Identifying Genetic Variations Overview Each of the cells in your body contains a copy of your genetic inheritance, your DNA which has been passed down to you, one half from your biological mother and one half from your biological father. This DNA determines physical features, like eye color and hair color, and can determine susceptibility to medical conditions like hypertension, heart disease, diabetes, and cancer. -
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. -
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 -
Representation for Discovery of Protein Motifs
From: ISMB-93 Proceedings. Copyright © 1993, AAAI (www.aaai.org). All rights reserved. Representation for Discovery of Protein Motifs Darrell ConklinT, Suzanne Fortier~, Janice Glasgowt Departments~t of Computing and Information Sciencet and Chemistry Queen’s University Kingston, Ontario, Canada K7L 3N6 [email protected] Abstract pattern of amino acid residues. Protein motifs can be roughly classified into four categories. Sequence There are several dimensions and levels of com- motifs are linear strings of residues with an implicit plexity in which information on protein mo- topological ordering. Sequence-structure motifs are tifs may be available. For example, one- sequence motifs with secondary structure identifiers at- dimensional sequence motifs may be associated tached to one or more residues in the motif. Structure with secondary structure identifiers. Alterna- motifs are 3D structural objects, described by posi- tively, three-dimensional information on polypep- tions of residue objects in 3D Euclidian space. Apart tide segments may be used to induce prototypical from a topological linear ordering on the residues, three-dimensional structure templates. This pa- structure motifs are free of sequence information. Fi- per surveys various representations encountered nally, structure-sequence motifs are combined 1D- in the protein motif discovery literature. Many 3D structures that associate sequence information with of the representations are based on incompatible a structure motif. Figure 1 illustrates these four types semantics, making difficult the comparison and of protein motifs, along with somefurther subclassifi- combination of previous results. To make better cations which are elaborated upon later in the paper. use of machine learning techniques and to pro- The first three motif types are discussed by Thornton vide for an integrated knowledge representation and Gardner (1989); the structure-sequence motif will framework, a general representation language -- be presented in this paper. -
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. -
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. -
A New Sequence Logo Plot to Highlight Enrichment and Depletion
bioRxiv preprint doi: https://doi.org/10.1101/226597; this version posted November 29, 2017. 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-NC-ND 4.0 International license. A new sequence logo plot to highlight enrichment and depletion. Kushal K. Dey 1, Dongyue Xie 1, Matthew Stephens 1, 2 1 Department of Statistics, University of Chicago 2 Department of Human Genetics, University of Chicago * Corresponding Email : [email protected] Abstract Background : Sequence logo plots have become a standard graphical tool for visualizing sequence motifs in DNA, RNA or protein sequences. However standard logo plots primarily highlight enrichment of symbols, and may fail to highlight interesting depletions. Current alternatives that try to highlight depletion often produce visually cluttered logos. Results : We introduce a new sequence logo plot, the EDLogo plot, that highlights both enrichment and depletion, while minimizing visual clutter. We provide an easy-to-use and highly customizable R package Logolas to produce a range of logo plots, including EDLogo plots. This software also allows elements in the logo plot to be strings of characters, rather than a single character, extending the range of applications beyond the usual DNA, RNA or protein sequences. We illustrate our methods and software on applications to transcription factor binding site motifs, protein sequence alignments and cancer mutation signature profiles. Conclusion : Our new EDLogo plots, and flexible software implementation, can help data analysts visualize both enrichment and depletion of characters (DNA sequence bases, amino acids, etc) across a wide range of applications. -
Introduction to Sequence Motif Discovery and Search the Complete
Introduction to sequence motif discovery and search EMBNET course Bioinformatics of transcriptional regulation Jan 28 2008 Christoph Schmid The complete genome era Components of transcriptional regulation Distal transcription-factor binding sites (enhancer) cis-regulatory modules Wasserman 5, 276-287 (2004) DNA-protein interaction Allen et al. © 1998 EMBL Jordan et al. © 1991 Prentice-Hall Sequence motifs sequence variants of site: ..A T C G C A.. ..T T G G A C.. ..T T G G T G.. ..A T C G G T.. matrix: A 2 0 0 0 1 1 (simplest version) C 0 0 2 0 1 1 G 0 0 2 4 1 1 T 2 4 0 0 1 1 + cutoff ! sequence logo: Title Representation of the binding specificity by a scoring matrix (also referred to as weight matrix) 1 2 3 4 5 6 7 8 9 A -10 -10 -14 -12 -10 5 -2 -10 -6 C 5 -10 -13 -13 -7 -15 -13 3 -4 G -3 -14 -13 -11 5 -12 -13 2 -7 T -5 5 5 5 -10 -9 5 -11 5 Strong C T T T G A T C T Binding site 5 + 5 + 5 + 5 + 5 + 5 + 5 + 3 + 5 = 43 Random A C G T A C G T A Sequence -10 -10 -13 + 5 -10 -15 -13 -11 - 6 = -83 Biophysical interpretation of protein binding sites Columns of a weight matrix characterize the specificity of base-pair acceptor sites on the protein surface. Weight matrix elements represent negated energy contributions to the total binding energy → weight matrix score inversely proportional to binding energy Motif search: Statistical over-representation of genomic sequence motifs Conserved motifs represent protein binding sites Putative conservation in nucleotide sequence (motif) position relative to: TSS other binding sites (protein complexes) -
Tools for Motif and Pattern Searching
TOOLS FOR MOTIF AND PATTERN SEARCHING Prat Thiru OUTLINE • What are motifs? • Algorithms Used and Programs Available • Workflow and Strategies • MEME/MAST Demo (online and command line) Protein Motifs DNA Motifs MEME Output Definitions • Motif: Conserved regions of protein or DNA sequences • Pattern: Qualitative description of a motif eg. regular expression C[AT]AAT[CG]X •Profile: Quantitative description of a motif eg. position weight matrix Patterns • Regular Expression Symbols ¾[ ] – OR eg. [GA] means G or A ¾{ } – NOT eg. {P,V} means not P or V ¾( ) – repeats eg. A(3) means AAA ¾X or N or “.” – any • Complex patterns representation difficult • Loose frequency information eg. [AT] vs 20%A 80%T Profiles Sequence Logos Algorithms • Enumeration • Probabilistic Optimization • Deterministic Optimization 1. Identify motifs 2. Build a consensus Enumeration • Exhaustive search: word counting method, count all n-mers and look for overrepresentation • Less likely to get stuck in a local optimum • Computationally expensive ¾YMF http://wingless.cs.washington.edu/YMF/YMFWeb/YMFInput.pl ¾Weeder http://159.149.109.9/weederaddons/locator.html Probabilistic Optimization • Uses a Gibbs sampling approach • One n-mer from each sequence is randomly picked to determine initial model. In subsequent iterations, one sequence, i, is removed and the model is recalculated. Pick a new location of motif in sequence i iterate until convergence • Assumes most sequences will have the motif ¾ AlignAce http://atlas.med.harvard.edu/cgi-bin/alignace.pl ¾ Gibbs Motif Sampler http://bayesweb.wadsworth.org/gibbs/gibbs.html Deterministic Optimization • Based on expectation maximization (EM) • EM: iteratively estimates the likelihood given the data that is present I. -
Degsampler: Gibbs Sampling Strategy for Predicting E3-Binding Sites with Position-Specific Prior Information
DegSampler: Gibbs sampling strategy for predicting E3-binding sites with position-specic prior information Osamu Maruyama ( [email protected] ) Kyushu University https://orcid.org/0000-0002-5760-1507 Fumiko Matsuzaki Kyushu University Research article Keywords: motif, substrate protein, E3 ubiquitin ligase, prior, posterior, disorder, collapsed, Gibbs sampling, DegSampler Posted Date: November 6th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-101967/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Maruyama and Matsuzaki RESEARCH DegSampler: Gibbs sampling strategy for predicting E3-binding sites with position-specific prior information Osamu Maruyama1* and Fumiko Matsuzaki2 Background Eukaryotic cells have two major pathways for degrad- ing proteins in order to control cellular processes and maintain intracellular homeostasis. One of the path- ways is autophagy, a catabolic process that deliv- ers intracellular components to lysosomes or vacuoles Abstract [1]. The other pathway is the ubiquitin-proteasome Background: The ubiquitin-proteasome system is system, which degrades polyubiquitin-tagged pro- a pathway in eukaryotic cells for degrading teins through the proteasomal machinery [2]. In the polyubiquitin-tagged proteins through the ubiquitin-proteasome system, an E3 ubiquitin ligase proteasomal machinery to control various cellular (hereinafter E3) selectively recognizes and binds to processes and maintain intracellular homeostasis. specific regions of the target substrate proteins. These In this system, the E3 ubiquitin ligase (hereinafter binding sites are called degrons [3]. E3) plays an important role in selectively It is important to identify the E3s and substrate recognizing and binding to specific regions of its proteins that interact with one another to character- substrate proteins. -
Bioinformatics: a Practical Guide to the Analysis of Genes and Proteins, Second Edition Andreas D
BIOINFORMATICS A Practical Guide to the Analysis of Genes and Proteins SECOND EDITION Andreas D. Baxevanis Genome Technology Branch National Human Genome Research Institute National Institutes of Health Bethesda, Maryland USA B. F. Francis Ouellette Centre for Molecular Medicine and Therapeutics Children’s and Women’s Health Centre of British Columbia University of British Columbia Vancouver, British Columbia Canada A JOHN WILEY & SONS, INC., PUBLICATION New York • Chichester • Weinheim • Brisbane • Singapore • Toronto BIOINFORMATICS SECOND EDITION METHODS OF BIOCHEMICAL ANALYSIS Volume 43 BIOINFORMATICS A Practical Guide to the Analysis of Genes and Proteins SECOND EDITION Andreas D. Baxevanis Genome Technology Branch National Human Genome Research Institute National Institutes of Health Bethesda, Maryland USA B. F. Francis Ouellette Centre for Molecular Medicine and Therapeutics Children’s and Women’s Health Centre of British Columbia University of British Columbia Vancouver, British Columbia Canada A JOHN WILEY & SONS, INC., PUBLICATION New York • Chichester • Weinheim • Brisbane • Singapore • Toronto Designations used by companies to distinguish their products are often claimed as trademarks. In all instances where John Wiley & Sons, Inc., is aware of a claim, the product names appear in initial capital or ALL CAPITAL LETTERS. Readers, however, should contact the appropriate companies for more complete information regarding trademarks and registration. Copyright ᭧ 2001 by John Wiley & Sons, Inc. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic or mechanical, including uploading, downloading, printing, decompiling, recording or otherwise, except as permitted under Sections 107 or 108 of the 1976 United States Copyright Act, without the prior written permission of the Publisher. -
A Tool for Detecting Base Mis-Calls in Multiple Sequence Alignments by Semi-Automatic Chromatogram Inspection
ChromatoGate: A Tool for Detecting Base Mis-Calls in Multiple Sequence Alignments by Semi-Automatic Chromatogram Inspection Nikolaos Alachiotis Emmanouella Vogiatzi∗ Scientific Computing Group Institute of Marine Biology and Genetics HITS gGmbH HCMR Heidelberg, Germany Heraklion Crete, Greece [email protected] [email protected] Pavlos Pavlidis Alexandros Stamatakis Scientific Computing Group Scientific Computing Group HITS gGmbH HITS gGmbH Heidelberg, Germany Heidelberg, Germany [email protected] [email protected] ∗ Affiliated also with the Department of Genetics and Molecular Biology of the Democritian University of Thrace at Alexandroupolis, Greece. Corresponding author: Nikolaos Alachiotis Keywords: chromatograms, software, mis-calls Abstract Automated DNA sequencers generate chromatograms that contain raw sequencing data. They also generate data that translates the chromatograms into molecular sequences of A, C, G, T, or N (undetermined) characters. Since chromatogram translation programs frequently introduce errors, a manual inspection of the generated sequence data is required. As sequence numbers and lengths increase, visual inspection and manual correction of chromatograms and corresponding sequences on a per-peak and per-nucleotide basis becomes an error-prone, time-consuming, and tedious process. Here, we introduce ChromatoGate (CG), an open-source software that accelerates and partially automates the inspection of chromatograms and the detection of sequencing errors for bidirectional sequencing runs. To provide users full control over the error correction process, a fully automated error correction algorithm has not been implemented. Initially, the program scans a given multiple sequence alignment (MSA) for potential sequencing errors, assuming that each polymorphic site in the alignment may be attributed to a sequencing error with a certain probability.