Searching BioSystems

BioSystems is available as part of the NCBI Entrez system and can be searched directly from the database page:

www.ncbi.nlm.nih.gov/BioSystems/

As with other Entrez databases, field-restricted queries in BioSystems give more precise search results. Many of the fields that work in the other Entrez molecular databases such as Organism and Title also are useful in BioSystems. All of the available fields can be browsed through the Preview/Index tab on the search page. The Limits tab provides a simple way to limit to certain types of records through pre-set fields. For example, the search can be limited to a specific source database, currently KEGG or EcoCyc. There is also a checkbox that allows restricting to organism-specific BioSystems, those with links to molecular records for a single species, or conserved BioSystems that group together orthologous organism specific pathways derived from KEGG reference pathways. Limiting to Conserved BioSystems provides more concise results and access to an overall summary of the pathway in all organisms. For example, a search with the phrase “purine metabolism” retrieves 3,509 records while limiting to conserved BioSystems or clicking the Conserved BioSystems filter tab provides a more concise set of only 26 records (Figure 1). As another example, the organism-specific record for purine metabolism in mouse is found directly with the following field-restricted query.

Figure 1

Search results in BioSystems using purine metabolism as a query. Both EcoCyc (BioCyc) and KEGG source records are found. The Conserved BioSystems filter tab at the top of the results selects KEGG reference pathways that summarize orthologous pathways (more...)

purine metabolism[Title] AND mouse[Organism]

BioSystems Records: Photosynthesis

The BioSystems database currently contains over 95 thousand pathways from the KEGG database including 255 conserved BioSystems and 286 Escherichia coli K-12 pathways from the EcoCyc portion of the BioCyc database. Figure 2 shows the BioSystems organism-specific record for photosynthesis from Arabidopsis thaliana (BioSystems ID 4001). The record has a description of the process from the source database, a thumbnail graphic that links to the larger diagram in the KEGG database, and a Tabbed Table of components and other aspects of the pathway (Genes, Proteins, Small Molecules, Related BioSystems, Citations and Comments). These components link to records in the NCBI Gene, Protein, PubChem, BioSystems, and PubMed databases.

Figure 2

The full BioSystems record for photosynthesis for Arabidopsis thaliana. The description and thumbnail image are from the KEGG database and link to the KEGG site. The Tabbed Table at the bottom provides access to corresponding Gene, Protein, Small Molecule (more...)

Tabbed Table of BioSystem Components

The Tabbed Table provides access to the components and other information linked to the pathway in the NCBI databases. Tabs include Genes, Proteins, Small Molecules, Related BioSystems, and Citations. The Arabidopsis genes and proteins corresponding to the filled boxes in the pathway diagram are listed in the Genes and Proteins tabbed sections of the table. The Small Molecule tab provides access to substrates, inhibitors, cofactors, and other non-protein entities involved in pathways from the NCBI PubChem database. Clicking on any entry will link to the corresponding Gene, Protein, or PubChem record. The link at the top of the table retrieves all records in the active tab. For example, clicking the top link in the Genes tab easily retrieves all 73 Arabidopsis genes involved in the photosynthetic pathway; clicking this link in the Small Molecules tab retrieves cofactors and substrates from PubChem (Figure 3). The Related BioSystems tab expands to display three types of related BioSystems: Linked BioSystems, Similar BioSystems, and Conserved BioSystems. Linked BioSystems are pathways that interact with the current pathway often providing substrates or receiving products of the current pathway. In this case, these are the antennal proteins light collecting system of photosynthesis (BioSystems ID 4002) and carbon fixation in photosynthetic organisms (BioSystems ID 4065). Similar BioSystems are pathways that share at least one identical protein sequence from the same source organism. Oxidative phosphorylation (BioSystems ID 4000) is the Similar Pathway to photosynthesis because it shares the subunits of the f-type ATPase. Finally, the Conserved BioSystem (BioSystems ID 340) is the reference pathway record for photosynthesis that gathers all orthologous pathways. The Conserved BioSystem includes the cyanobacterial components represented by unfilled boxes in the organism-specific pathway at the KEGG site. The remaining populated tab for the photosynthesis record, Citations, provides literature citations from the source database with links to the corresponding records in PubMed.

Figure 3

The Tabbed Table and linked records from the Arabidopsis photosynthesis BioSystem. Top panel. Tabbed Table with the Small Molecules tab selected showing PubChem records linked to the pathway. Center panel. Linked Gene and PubChem records in the corresponding (more...)

Links Menus: Related Data

In addition to the linked data available in the Tabbed Table, each BioSystems record has related data available as Links menus at the upper right of the summary or full BioSystems record (Figure 4). These are the Related BioSystems, Literature, Sequences, Small Molecules, and Other Links menus. The BioSystems, Literature, and Small Molecules menus access the same related data available in the Tabbed Table. Additional related data in the Sequences menu that are not available in the Tabbed Table are HomoloGene, Protein Clusters, and Conserved Domain records that are linked from the proteins in the pathway.

Figure 4

The Links menus from BioSystems records. The Sequences menu has Conserved Domains, HomoloGene, and Protein Clusters links in addition to the Proteins that are also in the Tabbed Table. Following the Conserved BioSystems link (left arrow) from the Arabidopsis (more...)

The HomoloGene and Protein Clusters related data identify homologs from selected eukaryotic and microbial genomes and allow comparisons of pathways across taxa. The linked Conserved Domains can give additional structural and functional information about the proteins in the pathway. The Other Links menu connects the BioSystem to the PubChem BioAssay database for small molecules in the pathway that have been classified as active in one of the assays. There are also links to the NCBI taxonomy database for organism-specific BioSystems, and to the Structure database if any of the proteins in the pathway are linked to a three-dimensional structure. The following example shows how to use these related data to find structures for the photosynthetic complexes starting from the Arabipdopsis organism-specific record.

Summary

The BioSystems database adds a new dimension to NCBI resources by connecting molecular, bioassay, and literature data to biological pathways and processes. This enables searches that for the first time can find all gene, protein records, and small molecules in a pathway for a particular organism. Moreover, integration with other NCBI databases allows comparisons of pathways across taxa and provides access to other data on structure and function of the biomolecules involved. Expanding the coverage of the Entrez system to pathways provides new connections among databases that should greatly increase the power of Entrez as a discovery system.

New BankIt Submission Tool

A new version of the BankIt sequence submission tool is available for testing. The new tool will eventually replace current version of BankIt after the test period. Please see the New BankIt page for more information: www.ncbi.nlm.nih.gov/WebSub/?tool=genbank

Bookshelf

The book, Familial Cancer Syndromes has been added to the NCBI Bookshelf. To browse this book go to www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=famcan

Microbial Genomes

Twenty-one finished microbial genomes were released between May 29 and July 6, 2009. The original sequence data files submitted to GenBank/EMBL/DDBJ are available on the FTP site: ftp.ncbi.nih.gov/genbank/genomes/Bacteria/. The RefSeq provisional versions of these genomes are also available: ftp.ncbi.nih.gov/genomes/Bacteria/.

PubChem

The American Library Association has selected PubChem as one of the Best Free Reference Web Sites 2009. More PubChem announcements are available at: pubchem.ncbi.nlm.nih.gov/pcnews.html and as an RSS feed.

BLAST

As previewed in the May 2009 NCBI News, COBALT multiple-sequence alignments can now be generated from protein BLAST results by clicking on the “Multiple Alignment” link. A direct submission form for generating protein multiple alignments using COBALT is also available in the Specialized BLAST section of the BLAST Homepage. The BLAST News page provides additional details about COBALT. The BLAST homepage also provides a “Tip of the Day” for more efficient use of the BLAST tool.