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MATLAB Bioinformatics Toolbox™ Users Guide (The MathWorks, Inc.) (z-library.sk, 1lib.sk, z-lib.sk)

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Read, analyze, and visualize genomic and proteomic data. Bioinformatics Toolbox provides algorithms and apps for Next Generation Sequencing (NGS), microarray analysis, mass spectrometry, and gene ontology. Using toolbox functions, you can read genomic and proteomic data from standard file formats such as SAM, FASTA, CEL, and CDF, as well as from online databases such as the NCBI Gene Expression Omnibus and GenBank®. You can explore and visualize this data with sequence browsers, spatial heatmaps, and clustergrams. The toolbox also provides statistical techniques for detecting peaks, imputing values for missing data, and selecting features. You can combine toolbox functions to support common bioinformatics workflows. You can use ChIP-Seq data to identify transcription factors; analyze RNA-Seq data to identify differentially expressed genes; identify copy number variants and SNPs in microarray data; and classify protein profiles using mass spectrometry data.

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Bioinformatics Toolbox™ User's Guide R2020a
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How to Contact MathWorks Latest news: www.mathworks.com Sales and services: www.mathworks.com/sales_and_services User community: www.mathworks.com/matlabcentral Technical support: www.mathworks.com/support/contact_us Phone: 508-647-7000 The MathWorks, Inc. 1 Apple Hill Drive Natick, MA 01760-2098 Bioinformatics Toolbox™ User's Guide © COPYRIGHT 2003–2020 by The MathWorks, Inc. The software described in this document is furnished under a license agreement. The software may be used or copied only under the terms of the license agreement. No part of this manual may be photocopied or reproduced in any form without prior written consent from The MathWorks, Inc. FEDERAL ACQUISITION: This provision applies to all acquisitions of the Program and Documentation by, for, or through the federal government of the United States. By accepting delivery of the Program or Documentation, the government hereby agrees that this software or documentation qualifies as commercial computer software or commercial computer software documentation as such terms are used or defined in FAR 12.212, DFARS Part 227.72, and DFARS 252.227-7014. Accordingly, the terms and conditions of this Agreement and only those rights specified in this Agreement, shall pertain to and govern the use, modification, reproduction, release, performance, display, and disclosure of the Program and Documentation by the federal government (or other entity acquiring for or through the federal government) and shall supersede any conflicting contractual terms or conditions. If this License fails to meet the government's needs or is inconsistent in any respect with federal procurement law, the government agrees to return the Program and Documentation, unused, to The MathWorks, Inc. Trademarks MATLAB and Simulink are registered trademarks of The MathWorks, Inc. See www.mathworks.com/trademarks for a list of additional trademarks. Other product or brand names may be trademarks or registered trademarks of their respective holders. Patents MathWorks products are protected by one or more U.S. patents. Please see www.mathworks.com/patents for more information.
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Revision History September 2003 Online only New for Version 1.0 (Release 13SP1+) June 2004 Online only Revised for Version 1.1 (Release 14) November 2004 Online only Revised for Version 2.0 (Release 14SP1+) March 2005 Online only Revised for Version 2.0.1 (Release 14SP2) May 2005 Online only Revised for Version 2.1 (Release 14SP2+) September 2005 Online only Revised for Version 2.1.1 (Release 14SP3) November 2005 Online only Revised for Version 2.2 (Release 14SP3+) March 2006 Online only Revised for Version 2.2.1 (Release 2006a) May 2006 Online only Revised for Version 2.3 (Release 2006a+) September 2006 Online only Revised for Version 2.4 (Release 2006b) March 2007 Online only Revised for Version 2.5 (Release 2007a) April 2007 Online only Revised for Version 2.6 (Release 2007a+) September 2007 Online only Revised for Version 3.0 (Release 2007b) March 2008 Online only Revised for Version 3.1 (Release 2008a) October 2008 Online only Revised for Version 3.2 (Release 2008b) March 2009 Online only Revised for Version 3.3 (Release 2009a) September 2009 Online only Revised for Version 3.4 (Release 2009b) March 2010 Online only Revised for Version 3.5 (Release 2010a) September 2010 Online only Revised for Version 3.6 (Release 2010b) April 2011 Online only Revised for Version 3.7 (Release 2011a) September 2011 Online only Revised for Version 4.0 (Release 2011b) March 2012 Online only Revised for Version 4.1 (Release 2012a) September 2012 Online only Revised for Version 4.2 (Release 2012b) March 2013 Online only Revised for Version 4.3 (Release 2013a) September 2013 Online only Revised for Version 4.3.1 (Release 2013b) March 2014 Online only Revised for Version 4.4 (Release 2014a) October 2014 Online only Revised for Version 4.5 (Release 2014b) March 2015 Online only Revised for Version 4.5.1 (Release 2015a) September 2015 Online only Revised for Version 4.5.2 (Release 2015b) March 2016 Online only Revised for Version 4.6 (Release 2016a) September 2016 Online only Updated for Version 4.7 (Release 2016b) March 2017 Online only Updated for Version 4.8 (Release 2017a) September 2017 Online only Updated for Version 4.9 (Release 2017b) March 2018 Online only Updated for Version 4.10 (Release 2018a) September 2018 Online only Updated for Version 4.11 (Release 2018b) March 2019 Online only Updated for Version 4.12 (Release 2019a) September 2019 Online only Updated for Version 4.13 (Release 2019b) March 2020 Online only Updated for Version 4.14 (Release 2020a)
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Getting Started 1 Bioinformatics Toolbox Product Description . . . . . . . . . . . . . . . . . . . . . . . 1-2 Key Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-2 Product Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-3 Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-3 Expected Users . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-4 Data Formats and Databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-5 Sequence Alignments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-7 Sequence Utilities and Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-8 Protein Property Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-9 Phylogenetic Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-10 Microarray Data Analysis Tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-11 Microarray Data Storage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-12 Mass Spectrometry Data Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-13 Graph Theory Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-15 Graph Visualization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-16 Statistical Learning and Visualization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-17 Prototyping and Development Environment . . . . . . . . . . . . . . . . . . . . . . . 1-18 Data Visualization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-19 Exchange Bioinformatics Data Between Excel and MATLAB . . . . . . . . . . 1-20 Using Excel and MATLAB Together . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-20 About the Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-20 Before Running the Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-20 Running the Example for the Entire Data Set . . . . . . . . . . . . . . . . . . . . . 1-21 Editing Formulas to Run the Example on a Subset of the Data . . . . . . . . 1-22 Using the Spreadsheet Link product to Interact With the Data in MATLAB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-23 v Contents
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Get Information from Web Database . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-26 What Are get Functions? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-26 Creating the getpubmed Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-26 High-Throughput Sequence Analysis 2 Work with Next-Generation Sequencing Data . . . . . . . . . . . . . . . . . . . . . . . 2-2 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-2 What Files Can You Access? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-2 Before You Begin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-3 Create a BioIndexedFile Object to Access Your Source File . . . . . . . . . . . . 2-3 Determine the Number of Entries Indexed By a BioIndexedFile Object . . . 2-3 Retrieve Entries from Your Source File . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-4 Read Entries from Your Source File . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-4 Manage Sequence Read Data in Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-6 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-6 Represent Sequence and Quality Data in a BioRead Object . . . . . . . . . . . . 2-7 Represent Sequence, Quality, and Alignment/Mapping Data in a BioMap Object . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-8 Retrieve Information from a BioRead or BioMap Object . . . . . . . . . . . . . 2-10 Set Information in a BioRead or BioMap Object . . . . . . . . . . . . . . . . . . . 2-12 Determine Coverage of a Reference Sequence . . . . . . . . . . . . . . . . . . . . 2-12 Construct Sequence Alignments to a Reference Sequence . . . . . . . . . . . 2-13 Filter Read Sequences Using SAM Flags . . . . . . . . . . . . . . . . . . . . . . . . . 2-14 Store and Manage Feature Annotations in Objects . . . . . . . . . . . . . . . . . 2-16 Represent Feature Annotations in a GFFAnnotation or GTFAnnotation Object . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-16 Construct an Annotation Object . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-16 Retrieve General Information from an Annotation Object . . . . . . . . . . . . 2-16 Access Data in an Annotation Object . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-17 Use Feature Annotations with Sequence Read Data . . . . . . . . . . . . . . . . 2-18 Visualize and Investigate Sequence Read Alignments . . . . . . . . . . . . . . . 2-21 When to Use the NGS Browser to Visualize and Investigate Data . . . . . . 2-21 Open the NGS Browser . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-21 Import Data into the NGS Browser . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-23 Zoom and Pan to a Specific Region of the Alignment . . . . . . . . . . . . . . . . 2-25 View Coverage of the Reference Sequence . . . . . . . . . . . . . . . . . . . . . . . 2-25 View the Pileup View of Short Reads . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-26 Compare Alignments of Multiple Data Sets . . . . . . . . . . . . . . . . . . . . . . . 2-26 View Location, Quality Scores, and Mapping Information . . . . . . . . . . . . 2-27 Flag Reads . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28 Evaluate and Flag Mismatches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28 View Insertions and Deletions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-29 View Feature Annotations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-29 Print and Export the Browser Image . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-30 Count Features from NGS Reads . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-31 vi Contents
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Identifying Differentially Expressed Genes from RNA-Seq Data . . . . . . . 2-41 Visualize NGS Data Using Genomics Viewer App . . . . . . . . . . . . . . . . . . . 2-69 Open the App . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-69 Add Tracks by Importing Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-69 Visualize Single Nucleotide Variation in Cytochrome P450 . . . . . . . . . . . 2-70 Sequence Analysis 3 Exploring a Nucleotide Sequence Using Command Line . . . . . . . . . . . . . . 3-2 Overview of Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-2 Searching the Web for Sequence Information . . . . . . . . . . . . . . . . . . . . . . 3-2 Reading Sequence Information from the Web . . . . . . . . . . . . . . . . . . . . . . 3-4 Determining Nucleotide Composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-5 Determining Codon Composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-8 Open Reading Frames . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-11 Amino Acid Conversion and Composition . . . . . . . . . . . . . . . . . . . . . . . . 3-13 Exploring a Nucleotide Sequence Using the Sequence Viewer App . . . . 3-15 Overview of the Sequence Viewer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-15 Importing a Sequence into the Sequence Viewer . . . . . . . . . . . . . . . . . . 3-15 Viewing Nucleotide Sequence Information . . . . . . . . . . . . . . . . . . . . . . . 3-17 Searching for Words . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-19 Exploring Open Reading Frames . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-22 Closing the Sequence Viewer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-25 Explore a Protein Sequence Using the Sequence Viewer App . . . . . . . . . 3-26 Overview of the Sequence Viewer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-26 Viewing Amino Acid Sequence Statistics . . . . . . . . . . . . . . . . . . . . . . . . . 3-26 Closing the Sequence Viewer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-28 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-29 Compare Sequences Using Sequence Alignment Algorithms . . . . . . . . . 3-30 Overview of Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-30 Find a Model Organism to Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-30 Retrieve Sequence Information from a Public Database . . . . . . . . . . . . . 3-31 Search a Public Database for Related Genes . . . . . . . . . . . . . . . . . . . . . . 3-33 Locate Protein Coding Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-34 Compare Amino Acid Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-36 View and Align Multiple Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-43 Overview of the Sequence Alignment App . . . . . . . . . . . . . . . . . . . . . . . . 3-43 Visualize Multiple Sequence Alignment . . . . . . . . . . . . . . . . . . . . . . . . . . 3-43 Adjust Sequence Alignments Manually . . . . . . . . . . . . . . . . . . . . . . . . . . 3-44 Rearrange Rows . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-52 Generate Phylogenetic Tree from Aligned Sequences . . . . . . . . . . . . . . . 3-54 vii
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Microarray Analysis 4 Managing Gene Expression Data in Objects . . . . . . . . . . . . . . . . . . . . . . . . 4-2 Representing Expression Data Values in DataMatrix Objects . . . . . . . . . . 4-5 Overview of DataMatrix Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-5 Constructing DataMatrix Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-5 Getting and Setting Properties of a DataMatrix Object . . . . . . . . . . . . . . . 4-6 Accessing Data in DataMatrix Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-6 Representing Expression Data Values in ExptData Objects . . . . . . . . . . . . 4-9 Overview of ExptData Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-9 Constructing ExptData Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-9 Using Properties of an ExptData Object . . . . . . . . . . . . . . . . . . . . . . . . . 4-10 Using Methods of an ExptData Object . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-10 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-11 Representing Sample and Feature Metadata in MetaData Objects . . . . . 4-12 Overview of MetaData Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-12 Constructing MetaData Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-13 Using Properties of a MetaData Object . . . . . . . . . . . . . . . . . . . . . . . . . . 4-15 Using Methods of a MetaData Object . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-15 Representing Experiment Information in a MIAME Object . . . . . . . . . . . 4-16 Overview of MIAME Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-16 Constructing MIAME Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-16 Using Properties of a MIAME Object . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-17 Using Methods of a MIAME Object . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-18 Representing All Data in an ExpressionSet Object . . . . . . . . . . . . . . . . . . 4-19 Overview of ExpressionSet Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-19 Constructing ExpressionSet Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-20 Using Properties of an ExpressionSet Object . . . . . . . . . . . . . . . . . . . . . 4-21 Using Methods of an ExpressionSet Object . . . . . . . . . . . . . . . . . . . . . . . 4-21 Visualizing Microarray Images . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-23 Overview of the Mouse Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-23 Exploring the Microarray Data Set . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-23 Spatial Images of Microarray Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-25 Statistics of the Microarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-33 Scatter Plots of Microarray Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-34 Phylogenetic Analysis 5 Using the Phylogenetic Tree App . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-2 Overview of the Phylogenetic Tree App . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-2 Opening the Phylogenetic Tree App . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-2 File Menu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-3 Tools Menu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-11 viii Contents
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Window Menu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-17 Help Menu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-18 ix
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Getting Started • “Bioinformatics Toolbox Product Description” on page 1-2 • “Product Overview” on page 1-3 • “Data Formats and Databases” on page 1-5 • “Sequence Alignments” on page 1-7 • “Sequence Utilities and Statistics” on page 1-8 • “Protein Property Analysis” on page 1-9 • “Phylogenetic Analysis” on page 1-10 • “Microarray Data Analysis Tools” on page 1-11 • “Microarray Data Storage” on page 1-12 • “Mass Spectrometry Data Analysis” on page 1-13 • “Graph Theory Functions” on page 1-15 • “Graph Visualization” on page 1-16 • “Statistical Learning and Visualization” on page 1-17 • “Prototyping and Development Environment” on page 1-18 • “Data Visualization” on page 1-19 • “Exchange Bioinformatics Data Between Excel and MATLAB” on page 1-20 • “Get Information from Web Database” on page 1-26 1
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Bioinformatics Toolbox Product Description Read, analyze, and visualize genomic and proteomic data Bioinformatics Toolbox provides algorithms and apps for Next Generation Sequencing (NGS), microarray analysis, mass spectrometry, and gene ontology. Using toolbox functions, you can read genomic and proteomic data from standard file formats such as SAM, FASTA, CEL, and CDF, as well as from online databases such as the NCBI Gene Expression Omnibus and GenBank®. You can explore and visualize this data with sequence browsers, spatial heatmaps, and clustergrams. The toolbox also provides statistical techniques for detecting peaks, imputing values for missing data, and selecting features. You can combine toolbox functions to support common bioinformatics workflows. You can use ChIP- Seq data to identify transcription factors; analyze RNA-Seq data to identify differentially expressed genes; identify copy number variants and SNPs in microarray data; and classify protein profiles using mass spectrometry data. Key Features • Next Generation Sequencing analysis and browser • Sequence analysis and visualization, including pairwise and multiple sequence alignment and peak detection • Microarray data analysis, including reading, filtering, normalizing, and visualization • Mass spectrometry analysis, including preprocessing, classification, and marker identification • Phylogenetic tree analysis • Graph theory functions, including interaction maps, hierarchy plots, and pathways • Data import from genomic, proteomic, and gene expression files, including SAM, FASTA, CEL, and CDF, and from databases such as NCBI and GenBank 1 Getting Started 1-2
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Product Overview Features The Bioinformatics Toolbox product extends the MATLAB® environment to provide an integrated software environment for genome and proteome analysis. Scientists and engineers can answer questions, solve problems, prototype new algorithms, and build applications for drug discovery and design, genetic engineering, and biological research. An introduction to these features will help you to develop a conceptual model for working with the toolbox and your biological data. The Bioinformatics Toolbox product includes many functions to help you with genome and proteome analysis. Most functions are implemented in the MATLAB programming language, with the source available for you to view. This open environment lets you explore and customize the existing toolbox algorithms or develop your own. You can use the basic bioinformatic functions provided with this toolbox to create more complex algorithms and applications. These robust and well-tested functions are the functions that you would otherwise have to create yourself. Toolbox features and functions fall within these categories: • Data formats and databases — Connect to Web-accessible databases containing genomic and proteomic data. Read and convert between multiple data formats. • High-throughput sequencing — Gene expression and transcription factor analysis of next- generation sequencing data, including RNA-Seq and ChIP-Seq. • Sequence analysis — Determine the statistical characteristics of a sequence, align two sequences, and multiply align several sequences. Model patterns in biological sequences using hidden Markov model (HMM) profiles. • Phylogenetic analysis — Create and manipulate phylogenetic tree data. • Microarray data analysis — Read, normalize, and visualize microarray data. • Mass spectrometry data analysis — Analyze and enhance raw mass spectrometry data. • Statistical learning — Classify and identify features in data sets with statistical learning tools. • Programming interface — Use other bioinformatic software (BioPerl and BioJava) within the MATLAB environment. The field of bioinformatics is rapidly growing and will become increasingly important as biology becomes a more analytical science. The toolbox provides an open environment that you can customize for development and deployment of the analytical tools you will need. • Prototype and develop algorithms — Prototype new ideas in an open and extensible environment. Develop algorithms using efficient string processing and statistical functions, view the source code for existing functions, and use the code as a template for customizing, improving, or creating your own functions. See “Prototyping and Development Environment” on page 1-18. • Visualize data — Visualize sequences and alignments, gene expression data, phylogenetic trees, mass spectrometry data, protein structure, and relationships between data with interconnected graphs. See “Data Visualization” on page 1-19. • Share and deploy applications — Use an interactive GUI builder to develop a custom graphical front end for your data analysis programs. Create standalone applications that run separately from the MATLAB environment. Product Overview 1-3
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Expected Users The Bioinformatics Toolbox product is intended for computational biologists and research scientists who need to develop new algorithms or implement published ones, visualize results, and create standalone applications. • Industry/Professional — Increasingly, drug discovery methods are being supported by engineering practice. This toolbox supports tool builders who want to create applications for the biotechnology and pharmaceutical industries. • Education/Professor/Student — This toolbox is well suited for learning and teaching genome and proteome analysis techniques. Educators and students can concentrate on bioinformatic algorithms instead of programming basic functions such as reading and writing to files. While the toolbox includes many bioinformatic functions, it is not intended to be a complete set of tools for scientists to analyze their biological data. However, the MATLAB environment is ideal for rapidly designing and prototyping the tools you need. 1 Getting Started 1-4
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Data Formats and Databases The Bioinformatics Toolbox lets you access many of the databases on the web and other online data repositories. It lets you copy data into the MATLAB workspace, and read and write to files with standard bioinformatic formats. It also reads many common genome file formats so that you do not have to write and maintain your own file readers. Web-based databases — You can directly access public databases on the Web and copy sequence and gene expression information into the MATLAB environment. The sequence databases currently supported are GenBank (getgenbank), GenPept (getgenpept), European Molecular Biology Laboratory (EMBL) (getembl), and Protein Data Bank (PDB) (getpdb). You can also access data from the NCBI Gene Expression Omnibus (GEO) Web site by using a single function (getgeodata). Get multiply aligned sequences (gethmmalignment), hidden Markov model profiles (gethmmprof), and phylogenetic tree data (gethmmtree) from the PFAM database. Gene Ontology database — Load the database from the Web into a gene ontology object (geneont). Select sections of the ontology with methods for the geneont object (getancestors (geneont), getdescendants (geneont), getmatrix (geneont), getrelatives (geneont)), and manipulate data with utility functions (goannotread, num2goid). Read data from instruments — Read data generated from gene sequencing instruments (scfread, joinseq, traceplot), mass spectrometers (jcampread), and Agilent® microarray scanners (agferead). Reading data formats — The toolbox provides a number of functions for reading data from common bioinformatic file formats. • Sequence data: GenBank (genbankread), GenPept (genpeptread), EMBL (emblread), PDB (pdbread), and FASTA (fastaread) • Multiply aligned sequences: ClustalW and GCG formats (multialignread) • Gene expression data from microarrays: Gene Expression Omnibus (GEO) data (geosoftread), GenePix® data in GPR and GAL files (gprread, galread), SPOT data (sptread), Affymetrix® GeneChip® data (affyread), and ImaGene® results files (imageneread) • Hidden Markov model profiles: PFAM-HMM file (pfamhmmread) Writing data formats — The functions for getting data from the Web include the option to save the data to a file. However, there is a function to write data to a file using the FASTA format (fastawrite). BLAST searches — Request Web-based BLAST searches (blastncbi), get the results from a search (getblast) and read results from a previously saved BLAST formatted report file (blastread). The MATLAB environment has built-in support for other industry-standard file formats including Microsoft® Excel® and comma-separated-value (CSV) files. Additional functions perform ASCII and low-level binary I/O, allowing you to develop custom functions for working with any data format. Data Formats and Databases 1-5
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See Also More About • “High-Throughput Sequencing” • “Microarray Analysis” • “Sequence Analysis” • “Structural Analysis” • “Mass Spectrometry and Bioanalytics” 1 Getting Started 1-6
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Sequence Alignments You can select from a list of analysis methods to compare nucleotide or amino acid sequences using pairwise or multiple sequence alignment functions. Pairwise sequence alignment — Efficient implementations of standard algorithms such as the Needleman-Wunsch (nwalign) and Smith-Waterman (swalign) algorithms for pairwise sequence alignment. The toolbox also includes standard scoring matrices such as the PAM and BLOSUM families of matrices (blosum, dayhoff, gonnet, nuc44, pam). Visualize sequence similarities with seqdotplot and sequence alignment results with showalignment. Multiple sequence alignment — Functions for multiple sequence alignment (multialign, profalign) and functions that support multiple sequences (multialignread, fastaread, showalignment). There is also a graphical interface (seqalignviewer) for viewing the results of a multiple sequence alignment and manually making adjustment. Multiple sequence profiles — Implementations for multiple alignment and profile hidden Markov model algorithms (gethmmprof, gethmmalignment, gethmmtree, pfamhmmread, hmmprofalign, hmmprofestimate, hmmprofgenerate, hmmprofmerge, hmmprofstruct, showhmmprof). Biological codes — Look up the letters or numeric equivalents for commonly used biological codes (aminolookup, baselookup, geneticcode, revgeneticcode). See Also More About • “Sequence Utilities and Statistics” on page 1-8 • “Sequence Analysis” • “Data Formats and Databases” on page 1-5 Sequence Alignments 1-7
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Sequence Utilities and Statistics You can manipulate and analyze your sequences to gain a deeper understanding of the physical, chemical, and biological characteristics of your data. Use a graphical user interface (GUI) with many of the sequence functions in the toolbox (seqviewer). Sequence conversion and manipulation — The toolbox provides routines for common operations, such as converting DNA or RNA sequences to amino acid sequences, that are basic to working with nucleic acid and protein sequences (aa2int, aa2nt, dna2rna, rna2dna, int2aa, int2nt, nt2aa, nt2int, seqcomplement, seqrcomplement, seqreverse). You can manipulate your sequence by performing an in silico digestion with restriction endonucleases (restrict) and proteases (cleave). Sequence statistics — Determine various statistics about a sequence (aacount, basecount, codoncount, dimercount, nmercount, ntdensity, codonbias, cpgisland, oligoprop), search for specific patterns within a sequence (seqshowwords, seqwordcount), or search for open reading frames (seqshoworfs). In addition, you can create random sequences for test cases (randseq). Sequence utilities — Determine a consensus sequence from a set of multiply aligned amino acid, nucleotide sequences (seqconsensus, or a sequence profile (seqprofile). Format a sequence for display (seqdisp) or graphically show a sequence alignment with frequency data (seqlogo). Additional MATLAB functions efficiently handle string operations with regular expressions (regexp, seq2regexp) to look for specific patterns in a sequence and search through a library for string matches (seqmatch). Look for possible cleavage sites in a DNA/RNA sequence by searching for palindromes (palindromes). See Also More About • “Sequence Alignments” on page 1-7 • “Sequence Analysis” • “Protein and Amino Acid Sequence Analysis” • “Data Formats and Databases” on page 1-5 1 Getting Started 1-8
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Protein Property Analysis You can use a collection of protein analysis methods to extract information from your data. You can determine protein characteristics and simulate enzyme cleavage reactions. The toolbox provides functions to calculate various properties of a protein sequence, such as the atomic composition (atomiccomp), molecular weight (molweight), and isoelectric point (isoelectric). You can cleave a protein with an enzyme (cleave, rebasecuts) and create distance and Ramachandran plots for PDB data (pdbdistplot, ramachandran). The toolbox contains a graphical user interface for protein analysis (proteinplot) and plotting 3-D protein and other molecular structures with information from molecule model files, such as PDB files (molviewer). Amino acid sequence utilities — Calculate amino acid statistics for a sequence (aacount) and get information about character codes (aminolookup). See Also More About • “Protein and Amino Acid Sequence Analysis” • “Structural Analysis” Protein Property Analysis 1-9
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Phylogenetic Analysis Phylogenetic analysis is the process you use to determine the evolutionary relationships between organisms. The results of an analysis can be drawn in a hierarchical diagram called a cladogram or phylogram (phylogenetic tree). The branches in a tree are based on the hypothesized evolutionary relationships (phylogeny) between organisms. Each member in a branch, also known as a monophyletic group, is assumed to be descended from a common ancestor. Originally, phylogenetic trees were created using morphology, but now, determining evolutionary relationships includes matching patterns in nucleic acid and protein sequences. The Bioinformatics Toolbox provides the following data structure and functions for phylogenetic analysis. Phylogenetic tree data — Read and write Newick-formatted tree files (phytreeread, phytreewrite) into the MATLAB Workspace as phylogenetic tree objects (phytree). Create a phylogenetic tree — Calculate the pairwise distance between biological sequences (seqpdist), estimate the substitution rates (dnds, dndsml), build a phylogenetic tree from pairwise distances (seqlinkage, seqneighjoin, reroot), and view the tree in an interactive GUI that allows you to view, edit, and explore the data (phytreeviewer or view). This GUI also allows you to prune branches, reorder, rename, and explore distances. Phylogenetic tree object methods — You can access the functionality of the phytreeviewer user interface using methods for a phylogenetic tree object (phytree). Get property values (get) and node names (getbyname). Calculate the patristic distances between pairs of leaf nodes (pdist, weights) and draw a phylogenetic tree object in a MATLAB Figure window as a phylogram, cladogram, or radial treeplot (plot). Manipulate tree data by selecting branches and leaves using a specified criterion (select, subtree) and removing nodes (prune). Compare trees (getcanonical) and use Newick-formatted strings (getnewickstr). See Also More About • “Sequence Utilities and Statistics” on page 1-8 • “Sequence Analysis” 1 Getting Started 1-10
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