Overview of The Pathway Tools Software

What is a Pathway/Genome Database and What is Pathway Tools?

• A PGDB is a bioinformatics DB that integrates genomic data with detailed functional annotations of the genome, such as descriptions of metabolic and signalling pathways, and of the regulatory network.

• The EcoCyc and HumanCyc DBs are PGDBs (see EcoCyc.org and HumanCyc.org).

• SRI's Pathway Tools software supports creation, editing, querying, visualization, and analysis of PGDBs. The software also allows users to publish a PGDB on the Web for querying by the scientific community.

• More than 75 groups have applied Pathway Tools to more than 200 genomes from all domains of life [list of external PGDBs on homepage].

Why Create a PGDB?

• Pathway Tools contains several powerful computational inference algorithms that help you extract more information from a genome:
  • It predicts the metabolic pathways of an organism from the genome.
  • It predicts what genes code for missing enzymes within the predicted metabolic pathways, typically identifying on the order of 100 new gene functions in a microbial genome.
  • It predicts the operons of a bacterium.

• The PGDB can aid analyses of gene expression, protein expression, and metabolomics experiments through the Pathway Tools Omics Viewers, which allow omics datasets to be graphically painted onto three system-level diagrams: a diagram of the full metabolic network of the organism, a diagram of the full regulatory network of the organism, and a diagram of the full genome of the organism. The software can produce animated displays of a series of omics measurements. It can also depict data from multiple omics datatypes simultaneously, such as mixing gene-expression and metabolomics data on one diagram.

  Click on images to see full-size.

• The PGDB will serve as a central resource for capturing, integrating, and disseminating new scientific findings about the organism. It will serve as a vehicle for tracking the evolving annotation of the genome, metabolic network, and genetic network of the organism, and for communicating that evolving knowledge through the Web. All genome annotations produced to date are incomplete, and contain significant numbers of errors. For organisms with active experimental communities, ongoing efforts are required to update those annotations to reflect new computational inferences, and new gene identifications and pathways reported in the experimental literature.

• The existence of an up-to-date genome annotation for an organism is a prerequisite for performing functional genomics studies of an organism because (a) one aim of functional genomics is to determine the functions of genes whose function is not already known, therefore, functional genomics efforts require access to the most accurate genome annotation possible; (b) the extensive new knowledge about gene function and gene regulation that will be gleaned from functional genomics studies must be integrated and disseminated to the scientific community, such as through a PGDB.

How is a PGDB Created?

• A PGDB is created by running a Pathway Tools software component called PathoLogic.

• The input required for PathoLogic is the annotated genome of the organism, such as in the form of a Genbank entry.

• The output produced by PathoLogic is a new PGDB for the organism.

• The process of creating a PGDB can take anywhere from a few days to a few weeks, depending on the size of the genome and the quality of the genome annotation.

What Types of Data and Operations does Pathway Tools Support?

• Metabolic and signalling pathways Full-sized image

• Metabolic enzymes, reactions, and small-molecule metabolites

• Transcription factors, operons, promoters, and transcription-factor binding sites

• Transport proteins

• Physical genome maps for closed and unclosed genomes Full-sized image

• Nucleic-acid sequences, and amino-acid sequences

• Interactively tracing metabolites through the metabolic network Full-sized image

• Finding dead-end metabolites in metabolic networks

• Identifying choke points (potential drug targets) in metabolic networks

• A whole suite of comparative operations, including comparing the full metabolic networks of two or more organisms

• Automatic generation of posters depicting the genome and the complete metabolic network

• BLAST searches against the genome

What Curation Tools Exist for PGDBs?

What are Other Advantages of Pathway Tools?

• It has a large user community, who have already successfully used the software to create database for many organisms.

• Extensive user documentation is available, as is an online information site at bioinformatics.ai.sri.com/ptools/

• Dr. Karp has received an NIH grant to support the user community of the software, and its further development

• The software is freely available to academic and government users, who own and therefore control the PGDBs that they create

How can I Learn More?

• Several publications about Pathway Tools are available from the BioCyc and Pathway Tools Publications Page

• See the Pathway Tools home page for extensive information including Pathway Tools tutorial powerpoint presentations

• The Pathway Tools software distribution includes extensive documentation

• Instructional videos on BioCyc

• Visit the BioCyc Web site at http://BioCyc.org/ to browse through several example PGDBs

How can I Contribute?

• Development of the PerlCyc Perl API to Pathway Tools by Lukas Mueller of Cornell University

• Development of the JavaCyc Java API to Pathway Tools by the TAIR project

• Development of the SBML output module by Jeremy Zucker of Harvard University