Introduction to BioCyc

The BioCyc collection of Pathway/Genome Databases (PGDBs) provides a reference on the genomes and metabolic pathways of thousands of sequenced organisms. BioCyc PGDBs are generated by software that predict the metabolic pathways of completely sequenced organisms, predict which genes code for missing enzymes in metabolic pathways, and predict operons. BioCyc also integrates information from other bioinformatics databases, such as protein feature and Gene Ontology information from UniProt. The BioCyc website provides a suite of software tools for database searching and visualization, for omics data analysis, and for comparative genomics and comparative pathway questions.

BioCyc databases (DBs) are organized into tiers according to the amount of manual updating they have received.

• Tier 1 PGDBs received intensive manual efforts, and are updated frequently [details of Tier 1].

• Tier 2 PGDBs were computationally generated by the PathoLogic program, and have received moderate manual updating. [details of Tier 2]

• Tier 3 PGDBs were computationally generated by PathoLogic, and have received no manual updates. [details of Tier 3]

PGDBs have been created by scientists outside SRI for organisms not present in BioCyc [details].

BioCyc Software Tools

• Visualization and Navigation: The BioCyc website enables visualization of individual metabolic pathways and of the complete metabolic map of an organism [example].

• Genome Browser: The BioCyc genome browser [example] enables analysis of positional genome datasets via tracks.

• Omics Data Analysis: Tools include statistical over-representation analysis, and visualization of gene expression, proteomics, or metabolomics data using the Omics Viewers, such as to produce animated views of time-course gene-expression experiments [example].

• SmartTables: Provide biologist-friendly analysis capabilities for groups of genes or metabolites.

• Metabolic Route Search: Search for reactions paths connecting specified metabolites in the metabolic network, with the option of adding new reactions from the MetaCyc DB.

• Comparative Analysis: Tools include comparison of pathways, metabolites, transporters, and regulatory networks -- (see menu command Analysis -> Comparative Analysis).

How to Learn More About BioCyc

The following additional information exists about the BioCyc site:

• Guided Tour: Examples of data present in BioCyc

• Website User's Guide: Instructions for using the BioCyc Website

• BioCyc User Guide: Information about the content of BioCyc DBs

• PGDB Concepts Guide: The ideas behind BioCyc

• Webinars: Interactive online seminars describing how to use BioCyc

• Publications: Articles about BioCyc databases and the Pathway Tools software

BioCyc data files may be downloaded to your site, and BioCyc data can be queried via web services. And you can install BioCyc on computers at your site, running it as a local Web server, and/or as a desktop application. The desktop application has a number of capabilities that the Web server does not [desktop mode]; we highly recommend it for frequent BioCyc users.

Definitions of Terminology on the BioCyc Website

Here we define a few key terms. See the glossary for more definitions.

Pathway/Genome Database (PGDB). A database that describes

• The genome of an organism -- its chromosome(s), genes, and genome sequence
• The product of each gene
• The metabolic network of the organism -- its pathways, reactions, enzymes, and metabolites
• The transporter complement of the organism
• The regulatory network of the organism, including its operons, transcription factors, and the interactions between transcription factors and their small-molecule ligands and DNA binding sites

Tier 1 PGDB. PGDBs in Tier 1 have received at least one year of literature-based curation by scientists. For example, the EcoCyc DB is the result of more than 20 person-years of effort to enter information from the E. coli literature about the metabolism, transport, and genetic regulatory processes of this organism.

Tier 2 PGDB. PGDBs in Tier 2 were generated by the PathoLogic program, which predicted their metabolic pathways; their operons (for bacteria only); and some missing enzymes in their predicted pathways (pathway hole fillers). The resulting PGDBs underwent manual review by a person to remove false-positive pathway predictions that they could detect, and to perform refinements such as defining protein complexes. The resulting PGDBs also underwent a period of literature-based curation, such as to enter metabolic pathways that had been experimentally elucidated in the organism but that were not inferred by PathoLogic. [list of Tier 2 PGDBs]

Tier 3 PGDB. PGDBs in Tier 3 were generated by PathoLogic, which predicted metabolic pathways, operons (for bacteria only), pathway hole fillers, and transport reactions. The resulting PGDBs did not undergo manual review of the pathway predictions, nor subsequent literature curation. Therefore, the pathway predictions should be treated with due caution. [list of Tier 3 PGDBs]

Pathway Tools Software. Pathway Tools is used to construct, update, visualize, query, and analyze PGDBs, such as the BioCyc collection. It is freely available to academics interested in creating PGDBs for organisms of interest to them. Components of Pathway Tools are:

• The Pathway/Genome Navigator supports querying, visualization, and analysis of PGDBs
• The Pathway/Genome Editors support interactive updating and refinement of PGDBs
• PathoLogic performs computational inferences such as pathway prediction
• MetaFlux enables creation of quantitative metabolic models from PGDBs

BioCyc: The collection of PGDBs at URL http://BioCyc.com/ is called the BioCyc Database Collection. EcoCyc and MetaCyc are component databases within the BioCyc collection.

BioCyc Organism Home Pages

BioCyc contains home pages for the following organisms. You can visit these pages as an easy entrez into the BioCyc genomes for these organisms.

EcoCyc	EcoCyc.org
MetaCyc	MetaCyc.org
HumanCyc	HumanCyc.org
Bacillus subtilis 168	BsubCyc.org
Helicobacter pylori	Helicobacter.biocyc.org
Listeria monocytogenes	Listeria.biocyc.org
Mycobacterium tuberculosis	Mycobacterium.biocyc.org
Pseudomonas aeruginosa	Pseudomonas.biocyc.org
Peptoclostridium difficile	Clostridium.biocyc.org
Saccharomyces cerevisiae	yeast.biocyc.org
Salmonella enterica	Salmonella.biocyc.org
Shigella flexneri	Shigella.biocyc.org
Vibrio cholerae	Vibrio.biocyc.org