VERSION 13.0 User’s Guide PATHWAY TOOLS ii Pathway Tools User’s Guide, Version 13.0 Copyright c 1996, 1999-2009 SRI International, 1997-1999 DoubleTwist, Inc. All rights reserved. Printed in the U.S.A. We gratefully acknowledge contributions to Pathway Tools, used by permission, from: Jeremy Zucker, Harvard Medical School The Laboratory of Christos Ouzounis, European Bioinformatics Institute DoubleTwist is a registered trademark of DoubleTwist, Inc. Medline is a registered trademark of the National Library of Medicine. Oracle is a registered trademark of Oracle Corporation. MySQL R is a registered trademark of MySQL AB in the United States, the European Union and other countries. The Generic Frame Protocol is Copyright c 1996, The Board of Trustees of the Leland Stanford Junior University and SRI International. All Rights Reserved. The Pathway Tools Software is Copyright c 1997-1999 DoubleTwist, Inc., SRI Interna- tional 1996, 1999-2007. All Rights Reserved. The EcoCyc Database is Copyright c SRI International 1996, 1999-2009, Marine Biologi- cal Laboratory 1996-2001, DoubleTwist Inc. 1997-1999. All Rights Reserved. The MetaCyc Database is Copyright c SRI International 1999-2009, Marine Biological Laboratory 1998-2001, DoubleTwist Inc. 1998, 1999. All Rights Reserved. Allegro Common Lisp is Copyright c 1985-2009, Franz Inc. All Rights Reserved. All other trademarks are property of their respective owners. Any rights not expressly granted herein are reserved. This product may include data from BIND (http://blueprint.org/bind/bind. php) to which the following two notices apply: (1) Bader GD, Betel D, Hogue CW. (2003) BIND: the Biomolecular Interaction Network Database. Nucleic Acids Res. 31(1):248-50 PMID: 12519993 (2) This data is distributed in the hope that it will be useful, but WITHOUT ANY WAR- RANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. The dictionary used by the Pathway Tools spell checker was provided courtesy of www.biology-online.org. SRI International 333 Ravenswood Ave. Menlo Park, CA 94025 U.S.A. [email protected] iii iv Contents Contents v Preface xvii 1 Introduction to the Pathway Tools Software 1 1.1 Databases and Tools . 1 1.1.1 Databases . 2 1.1.2 Pathway Tools . 3 2 Invoking Pathway Tools 5 2.1 Pathway Tools Init File . 6 2.1.1 Parameters for Running in Web Server Mode . 6 2.1.2 Additional Parameters for Running in Web Server Mode . 6 2.1.3 Parameters Used when Accessing PGDBs within a MySQL or Ora- cle Server . 8 2.1.4 Parameters Associated with User Accounts Defined for a Pathway Tools Web Server . 8 2.2 X-Windows Basics . 9 2.3 Running Pathway Tools from the Command Line . 9 2.3.1 Command Line Arguments . 11 3 Pathway/Genome Navigator 17 3.1 Using the Mouse To Navigate and Issue Commands . 17 3.2 Menus and Dialogs . 18 v 3.2.1 Menu Bar . 18 3.2.2 Single-Choice Menus . 18 3.2.3 Multiple-Choice Menus . 18 3.2.4 Dialogs . 18 3.2.5 Aborting Out of Menus and Dialogs . 19 3.3 Organism Summary Display . 19 3.4 Single Organism Display . 20 3.5 Notion of Current Organism . 21 3.6 Examples . 22 3.7 Query Facilities . 23 3.7.1 Direct Queries . 24 3.7.2 Indirect Queries: Navigation . 25 3.7.3 History List . 26 3.7.4 Programmatic Queries . 26 3.8 Object Displays and Queries . 27 3.8.1 Shared Display Characteristics . 28 3.8.2 Systems Level Overviews . 31 3.8.3 Pathways . 54 3.8.4 Reactions . 58 3.8.5 Proteins . 59 3.8.6 RNAs . 62 3.8.7 Genes . 62 3.8.8 Compounds . 64 3.8.9 Transcription Units . 65 3.8.10 Genome Browser . 66 3.8.11 Displaying External Tracks on the Genome Browser . 69 3.8.12 Comparative Genome Browser . 72 3.9 Advanced Queries using the BioVelo querying language . 73 vi 3.10 Miscellaneous Commands and Tools . 73 3.10.1 Home . 73 3.10.2 Back . 73 3.10.3 Forward . 73 3.10.4 History . 74 3.10.5 Next Answer . 74 3.10.6 Clone . 74 3.10.7 Print . 74 3.10.8 Tools Menu . 75 3.10.9 Help . 80 3.10.10 Exiting Pathway Tools . 80 3.10.11 User Preferences . 80 3.10.12 Keyboard Shortcuts . 84 3.10.13 Tips . 85 3.11 Comparative Operations . 86 3.11.1 Global Comparative Analyses . 86 3.11.2 Sequential Comparison . 89 3.11.3 Parallel Comparison . 91 4 The Import/Export Facility 97 4.1 Pathway Import/Export . 98 4.2 SBML Export . 99 4.3 Genbank Format Export . 99 4.4 Linking Table Export . 100 4.5 Full Flat File Dump . 100 4.6 Frame Import/Export . 100 4.6.1 Frame Export . 101 4.6.2 Frame Import . 103 4.6.3 Supported file formats for frame import and export: . 106 vii 4.7 Importing citations from PubMed . 107 5 Database Sharing Via the PGDB Registry 109 5.1 Downloading PGDBs from the Registry . 110 5.2 Publishing PGDBs in the Registry . 110 5.2.1 Details of what happens during each step: . 111 5.2.2 Preliminary Step: Setting Preferences . 112 5.2.3 Registering a PGDB . 114 5.2.4 About Click-Through Licenses . 116 6 PathoLogic: Automated Creation of Pathway/Genome Databases 117 6.1 Overview of PathoLogic Execution . 118 6.1.1 Database Generation Perspective . 118 6.1.2 PathoLogic Operation . 119 6.2 PathoLogic Input File Formats . 120 6.2.1 File genetic-elements.dat . 120 6.2.2 The PathoLogic File Format . 121 6.2.3 GenBank File Format . 124 6.2.4 Specifying Gene Ontology Terms . 127 6.2.5 Directory Structure for a PGDB . 128 6.3 Creating a Pathway/Genome Database . 129 6.3.1 Invoke PathoLogic . 129 6.3.2 Create New Organism . 130 6.3.3 Create genetic-elements.dat File . 132 6.3.4 Specify Reference PGDB . 132 6.3.5 Trial Parse . 134 6.3.6 Build Pathway/Genome Database . 136 6.3.7 Metabolic Pathway Prediction . 137 6.3.8 Update Build for New Annotation . 143 viii 6.3.9 Adding or Replacing a Sequence File . 145 6.3.10 PGDB Housekeeping Tasks . 145 6.4 Refining the PGDB . 148 6.4.1 Refine: Assign Probable Enzymes . 148 6.4.2 Refine: Rerun Name Matcher . 152 6.4.3 Refine: Rescore Pathways . 152 6.4.4 Refine: Create Protein Complexes . ..