A biosystem, or biological system, is a group of molecules that interact in a biological system. One type of biosystem is a biological pathway, which can consist of interacting genes, proteins, and small molecules. Another type of biosystem is a disease, which can involve components such as genes, biomarkers, and drugs.

An understanding of the components, products, and biological effects of biosystems can lead to better understanding of biological processes in normal and disease states, elucidation of possible drug effects and side effects, and other insights to complex processes that have implications for health and medicine.

The COX portion of the Arachidonic acid metabolism pathway, for example, metabolizes lipids commonly found in the cell membrane into prostaglandins, which are involved in regulation of neuronal activity. This pathway has an important role in pain and inflammation. Specifically, the protein encoded by human PTGS1 gene is involved in the conversion of prostaglandin PGG2 into inflammation-causing prostaglandin PGH2. Aspirin has been shown to bind to the PTGS1 gene product (prostaglandin-endoperoxide synthase 1), blocking that enzyme's ability to produce PGH2 and thereby reducing pain and inflammation.

To illustrate the ways in which the NCBI BioSystems database can be used, the Arachidonic acid metabolism pathway is used in illustrations and examples threaded through this help document.

Centralize access to existing biosystems databases

Numerous publicly browsable biosystems databases are accessible throughout the Web. The NCBI BioSystems database was designed to centralize access to those existing databases and to integrate their records with associated data types (genes, proteins, small molecules, etc.) as noted below. The current source databases are listed in the section on "content of the BioSystems database."

Connect biosystems records with associated literature, molecular, and chemical data

Upon submission to the NCBI BioSystems database, records from source databases go through an automated data processing pipeline to identify associated literature, molecular, and chemical data throughout the Entrez system, and to then establish connections among those data sets. This allows seamless traversal from a biosystem record to (a) sequence, 3D structure, and chemical data for the biosystem components; (b) PubMed records for articles about the biosystem; and (c) additional information associated with the biosystem components, such as functional and evolutionary classification of protein components in the Conserved Domain Database (CDD), 3D protein structures in the Molecular Modeling Database (MMDB), biological activity data for component small molecules in the PubChem BioAssay database, and phenotypic information in OMIM.

Facilitate computation on biosystems data

Many biosystem databases provide detailed diagrams that permit close examination of the components and biochemical steps within individual pathways. The NCBI BioSystems database was developed as a complementary project to list and categorizes the genes, proteins, and small molecules involved in each biological system, and to facilitate computation on biosystems data.

For example, using the human Arachidonic acid metabolism pathway (mentioned in "what is a biosystem?") as an illustration, the NCBI BioSystems database can be used to answer such questions as the following:

• What genes, proteins, and small molecules are involved in this pathway?

• Example: the "Genes," "Proteins," and "Small molecules" folder tabs in the BioSystems record bsid82991: human Arachidonic acid metabolism list the pathway components in each of those categories.

• Where in the metabolic pathway do my gene(s), protein(s), or small molecule(s) of interest occur?

• Example: The PTGS1 gene (GeneID 5742) is included in the BioSystems component list for the human arachidonic acid metabolism pathway (bsid82991). If you activate the checkbox for GeneID 5742 in the "Genes" folder tab of the record, then use the option to Highlight Selected Records in Source Database, the gene will be highlighted with a red outline in the corresponding KEGG record for Arachidonic Acid Metabolism. (In that view, the PTGS1 gene product is displayed as Enzyme Commission (EC) number 1.14.99.1; see illustrated example.)

• What biosystems include a particular component of interest?

• Example 1: To retrieve biosystems that include the human PTGS1 gene as a component, you can search the GeneID field of the BioSystems database for that component's unique identifier (in this case, 5742). The biosystems that are retrieved have been associated with that gene through the method descibed in the data processing section of this document.

• Example 2: To retrieve biosystems that include prostaglandin G2 (PGG2, CID 5280883) as a component, you can search the Compound ID (CID) field of the BioSystems database for that component's unique identifier (in this case, 5280883). The biosystems that are retrieved have been associated with that CID through the method descibed in the data processing section of this document.

• In what other organisms is this pathway found?

• Example: The BioSystems record bsid82991: human Arachidonic acid metabolism includes a "Related BioSystems : Conserved BioSystems" folder tab, which provides a link to the conserved biosystem bsid366. Additional organism-specific biosystems are then listed under the "Related BioSystems" folder tab of that record.

Source Databases

The content of the BioSystems database currently comes from the following sources. Articles cited in the References section provide more information about each of the source databases.

KEGG	KEGG: Kyoto Encyclopedia of Genes and Genomes (http://www.genome.jp/kegg/) by the Kanehisa Laboratory of the Bioinformatics Center, Institute for Chemical Research, Kyoto University, Kyoto, Japan.  (read more...)
BioCyc	BioCyc (http://biocyc.org/) is a collection of organism-specific pathway/genome databases (PGDBs), and the EcoCyc (http://ecocyc.org/) subset of BioCyc is included in the NCBI BioSystems database. (read more...)
Reactome	Reactome (http://www.reactome.org/) is a curated knowledge base of biological pathways, and the human subset of Reactome is included in the NCBI BioSystems database. (read more...)

The content and of BioSystems database records reflect the data provided by the source, and some special functions may vary by source as well. For example, thumbnail images of biosystem diagrams and the ability to highlight selected components in a full size image of the biosystem diagram are currently available for KEGG records. The central functions of the BioSystems database, however, are available for all records, such as the listing and categorization of biosystem components and links to related data throughout the Entrez system.

If you want to limit search results to records from a particular source, you can use the SourceName field, as described in the Search Fields section of this help document.

If you are interested in depositing data into the BioSystems database, please contact biosystems.help@ncbi.nlm.nih.gov.

Record Types

Two categories of records are currently available in the BioSystems database, and additional types will be added as they become available.

organism specific biosystem	an organism-specific biosystem that typically includes genes, proteins, and small molecules as components. (If similar biosystems are found in other organisms, you can retrieve them by opening the corresponding conserved biosystem record, accessible under the Related BioSystems folder tab, and then viewing the set of organism-specific biosystems that fall under the conserved biosystem.)
conserved biosystem	canonical biosystems that are used to group together orthologous, organism specific biosystems. These records are derived from "reference pathways" in the KEGG database. (The organism specific biosystems that fall under a canonical biosystem are accessible under that record's Related BioSystems folder tab.)

For example, the conserved biosystem for arachidonic acid metabolism, bsid366, encompasses numerous organism-specific biosystems, including bsid82991 for human arachidonic acid metabolism.

If you want to limit search results to a particular category of record, you can select the desired record type using the Limits folder tab on the BioSystems search page, or use the Filter field as described in the Search Fields section of this help document (e.g., add the following term and search field to your query: AND "conserved biosystem"[Filter]).

How are the data processed at NCBI?

Extract descriptive text:  When biosystems records are deposited by a source database, an archival copy of each record is made and text blocks such as biosystem name, description, and comments are then extracted into the BioSystems database.

 

Extract thumbnail images:  If a source database provides a thumbnail image of a biosystem diagram, the image is placed in the corresponding BioSystems database record and links to a full-size image that resides on the source database web site.

 

At present, thumbnail images and the ability to highlight selected components (genes, proteins, small molecules) in a full size image of the biosystem diagram are currently available only for KEGG records. In BioSystems records that do not contain a thumbnail image, a full size diagram may be available at the source database by following the link in the BioSystem record for the source's accession number.

Create direct links:  Each biosystem record has one-to-one relationships with specific records in other Entrez databases, particularly for biosystem components in the Entrez Gene, Protein, and PubChem Compound databases, as well as PubMed articles cited in the biosystem record. Reciprocal links between the biosystem record and these component and literature records are created by parsing the source database's record for the following unique identifiers:

 

	Genes	GeneIDs present in the source record are parsed out and links are then established to the corresponding records in the Entrez Gene database. The links are made available in both the Links menus on DocSum pages of search results and in the folder tabs shown on individual BioSystem records. If only gene names but not GeneIDs are provided in the source record, those gene names are parsed out and listed as components in the genes folder tab of individual BioSystem records but they are not linked to Entrez Gene records and are not included in the Sequences/Genes Links menu in DocSum pages. Links are also established to Gene IDs that correspond to the protein sequence GI numbers mentioned below; for example, if one of those protein GIs is cited directly in a Gene record, a link to that Gene record is made.
	Proteins	Protein GI numbers present in the source record are parsed out and links are then established directly to the corresponding sequence records in the Entrez Protein database. If the source record contains protein accession numbers, the current GI number for each accession is determined and a link to the corresponding protein sequence record is made using the GI number. In addition, the set of links to protein sequences is expanded in the following ways: (a) If any GI numbers are for RefSeq records, links to corresponding UniProt/Swiss-Prot records are also made. (b) if any other record(s) in the Entrez Protein database contains an identical sequence to the one present in the cited GI and also share the same Taxonomy ID (TaxID), links to those identical sequence records are established as well. Technical note: In the data processing pipeline at NCBI, protein sequence records that contain an identical sequence, regardless of TaxID, are placed in a protein identity group (PIG), and each group is given a stable identification number (PIG ID). For step (b) above, links are made to all PIG members that have the same TaxID as the protein GI cited in the source biosystem record. (The proteins are then listed in the protein folder tab of a biosystem record and sorted by PIG ID so identical sequences can be easily spotted.)
	Small Molecules	Records from source databases are parsed for small molecule identification numbers, including PubChem Compound IDs (CIDs), PubChem Substance IDs (SIDs), and external registry names such as local identifiers assigned to a substance by a the source database. The types of links that are made depend upon the type of identifiers that were found: If SIDs are present in the source record, links are established to the corresponding PubChem Substance records and to associated CIDs in PubChem Compound. If CIDs are present in the source record, links to the corresponding PubChem Compound records are made (however, the links are not extended to associated PubChem Substances). If external registry names are present, those identifiers are mapped to the corresponding SIDs and links are made to those records in PubChem Substance as well as to associated CIDs in PubChem Compound.
	Literature	If the source record includes PubMed identifiers (PMIDs) for journal articles about the biosystem, the PMIDs are parsed and links are established to the corresponding records in the PubMed database. If the source record contains a text citation but no PMID, the citation is displayed in the folder tabs section of the biosystem record, but no link to PubMed is provided.
	Taxonomy	Depositors provide the Taxonomy ID (TaxID) of the source organism for organism specific biosystems. These TaxIDs are parsed and links to the corresponding information in the NCBI Taxonomy database are then established. Taxonomic information is not extracted from conserved biosystems; however, the individual organisms that are encompassed by a conserved biosystem are listed in the Organism Specific BioSystems folder tab of the conserved biosystem record.

Calculate indirect links:  Records that are directly linked to a biosystem may in turn have links to other Entrez databases and records. For example, a biosystem record that includes a small molecule component will have a direct link to the PubChem Compound record for that small molecule. If the PubChem Compound record in turn has a link to information about the molecule's biological activity in the PubChem BioAssay Database, a link between the BioSystem record and the BioAssay record will also be established. These types of connections represent indirect (second generation) links.

The indirect links that are calculated for each BioSystem record are explained in a separate part of this help document and include: Literature (OMIM); Sequences (Conserved Domains, HomoloGene, Protein Clusters); and Other Links (BioAssays vis Actives, BioAssays vis Target, Structures).

Identify relationships among biosystems:   Two or more biosystem records are considered related if any one of the following conditions have been met:

the source database has explicitly stated the biosystems are connected in some way (Linked BioSystem) the biosystems share at least one identical protein sequence from the same source organism (Similar BioSystems). In other words, the shared protein is in the same protein identity group (PIG) and has the same Taxonomy ID (TaxID). the biosystems have an evolutionary relationship, such as an Organism Specific BioSystem that is an instance of a canonical, Conserved BioSystem. For example, human arachidonic acid metabolism (bsid82991) is an organism-specific instance of the conserved biosystem for arachidonic acid metabolism (bsid366). The conserved biosystem record, in turn, links back to the human and other organism-specific instances of the biosystem, reflecting the relationships specified by the source database, KEGG. biosystems that have a functional relationship with each other, either as a Superset of smaller biological processes or a Subset of (or small reaction within) a larger biological process. For example, "Phase 1 - Functionalization of compounds" (bsid105699) is a superset biosystem that includes "COX reactions" (bsid105711) as one of its subset biosystems, reflecting the hierarchical organization of those biosystems specified by the source database, Reactome. The superset/subset relationships reflect the node immediately above/below the biosystem being viewed. In each case, reciprocal links are created among the related biosystems and are accessible from the Links menus on the DocSum page of search results and from the folder tabs on individual biosystem records.

Allowable search terms

text terms (key words):  A wide variety of text terms, such as names of biosystems, genes, proteins, and small molecules can be used to search the BioSystems database. You can also search for other words that might be present in the title, comments, or other text containing fields of a record. Because terminology can vary across records, it can be helpful to include synonyms in your query (e.g., PTGS1 OR "prostaglandin endoperoxide synthase 1"). It is also possible to search for a word stem by using an asterisk (*) as a wild card; for example, arachidon* will retrieve records with terms such as arachidonate, arachidonic, arachidonoyl. The Entrez Help document provides additional information about truncating search terms in this way.

unique identifiers:  BioSystem records can be retrieved by searching for the unique identifiers of their components, such as GeneIDs, protein sequence GI numbers or accession numbers, and CIDs, SIDs, or external registry names of small molecules. The retrieved biosystems have been associated with those components through the methods descibed in the data processing/create direct links section of this document.

organism:  To retrieve biosystem records for a specific organism or organism group, you can enter its common name (e.g., human) or scientific name (e.g., Homo sapiens), or other taxonomic node (e.g, Primates) in the Organism [orgn] search field. Note that a search of the organism field will retrieve only organism specific biosystems that fall under the specified taxonomic node. To find corresponding conserved biosystems that are present in numerous organisms, simply follow the "related biosystems/conserved biosystems" link from the biosystem record(s) of interest.

database subset:  It is possible to retrieve records from a specified database subset. For example, the SourceName search field allows you to retrieve records from a specific source database. The Filter field allows you to limit a search to specific record types or to records that have links to another Entrez database of interest; for example, a search for biosystems_structure[filter] will retrieve biosystem records that have links to the Entrez Structure database, and a search for biosystems_omim[filter] will retrieve biosystem records that have links to the Online Mendelian Inheritance in Man (OMIM) database.

and more...  The biosystems database can also be searched by terms that appear in any of the other search fields.

Search Methods

A variety of techniques can be used to search the database, offering varying degrees of control over your query. In some cases, they offer alternative ways of executing the same search (as is true for sample searches #4, #5, and #6 below), with each method offering different benefits. The search methods include:

• basic
• advanced (Limits, History, Preview/Index, and Index button tips)
• complex Boolean
• batch query

Method	Description	Example
Basic	Just enter search terms without specifying search fields, other limits, or Boolean operators. Open the Details folder tab on the search results page to see exactly how Entrez parsed and handled your query.	Search #1: human arachidonic acid will retrieve biosystems with those terms anywhere in the record. Some of the records might be from organisms other than human because we did not limit that search term to the Organism search field. Therefore, we will also retrieve other species biosystems if they happen to contain the term "human" in a comment or some other field of the record. Similarly, the term "arachidonic acid" can appear anywhere in the record. Some biosystems might have it in the title, and others might have it as a component.
Advanced	Advanced search methods allow you to exercise greater control over your search, for example, by specifying which search field to use for each query term, limiting search results to a particular type of record or source database, or refining your search in other ways. This can be done by using the folder tabs: or by entering a Complex Boolean query
Limits	The Limits folder tab allows you to view the list of search fields. You can enter each search term or phrase separately, selecting the desired search field for each one. Then use History to combine the searches, as shown below. The Limits page also provides other commonly used options, as check boxes and/or pull-down menus, for restricting your search results. These limits are based on commonly used search terms and/or fields, and are placed on the Limits page for easy access. For example, you can select the "BioSystem Type" radio button for conserved biosystems as a shortcut for adding the following term and search field to your query:   AND "conserved biosystem"[Filter] IMPORTANT NOTE: Once you have used a particular Limit, a small check box on the Limits folder tab will appear. As long as the checkbox remains activated, the Limit(s) that were just applied to your search will continue to be applied to all subsequent searches. Therefore, remember to deselect that checkbox if you do not want the limit applied to your next search. You can then select new limits for subsequent searches, if desired. activated deactivated	Search #2: On the BioSystems search page, click on the Limits folder tab, select the Organism search field, and enter the following query: human and press "GO". That will retrieve only biosystems found in human. Search #3: Open the Limits tab again and clear your previous search. Change the search field selection to Title, enter the following query: arachidonic acid and press "GO". That will retrieve only records containing those terms in the title, or name, of a biosystem. Now you can use the History folder tab to combine the searches, as shown in Search #4 below.
History	The History folder tab displays the searches you have done in the current database. Search History will be lost after eight hours of inactivity. (To save a search indefinitely, click on the search # and select "Save in My NCBI.") You can combine or subtract searches from each other by entering the search numbers and the AND, OR, or NOT Boolean operators in the query box, for example: #2 AND #3. If the query contains several search numbers and Boolean operators, the Boolean operators are processed from left to right unless parentheses are used for nesting. If parentheses are used, the portions of the query in parentheses will be processed first, then the remaining Boolean operators will be processed from left to right. The search numbers might not be consecutive if you have done intervening searches in other databases. This is because search numbers are assigned consecutively to all the searches you have done across the Entrez system, while "History" only shows the subset of searches you have done in a particular database. See the PubMed help document for additional details about History.	Search #4: You can enter the following character string in the query box at the top of the History page to combine the two searches above: #2 AND #3 That will retrieve only records that contain "human" in the Organism field and "arachidonic acid" in the Title field. Compare the retrieval from this search with that of the sample basic search above. (Note that your search numbers might be different from those shown here, if you did earlier searches in the Entrez system before trying these examples.)
Preview/Index	The Preview/Index page allows you to build your query step by step, adding a new search term and selecting a new search field at each step. The text box at the top of the page shows your active query. The Preview button displays the number of hits your search retrieves and keeps you on the "Preview/Index" page so you can continue building your query. The Go button displays the records retrieved by your search (as a DocSum search results page). The bottom area of the page is like a worksheet, where you can: (1) Select the Search Field of interest using the pull-down menu. (2) Enter a term(s) in the text box beside the search field menu. (3) Then press any one of the following buttons: The Preview button will simply add the new term/searchfield combination to the active query at the top of the page. (The term will be added with a Boolean AND; use the "OR" or "NOT" buttons if one of those Boolean operators is desired instead.) The Index will allow you to first browse the selected search field's index before adding a term(s) to the active query (see tips below). The AND, OR, NOT buttons will append the selected term(s) to the active query. If multiple terms are selected from the index window, they will be ORed together before being appended to the active query. Tips on using the Index button on the "Preview/Index" page: The Index button allows you to browse the index of any Search Field. If you select a search field and press the Index button without entering a term in the box, you will be taken to the top of the index. If you enter a term first, you will be taken to the part of the index that contains your term (or the closest alphabetical location, if your term is not present in the index). The number of records that contain the term will appear in parentheses. You can also browse the index to explore the variety of terms available (for example, select "All Fields", enter "Huntington", and press the Index button to see additional spellings and/or related terms, such as Huntington disease, Huntington's, Huntington's disease). To select a range of terms from the index, use the Shift key while selecting the first and last term. Then use the AND, OR, or NOT buttons to add that group of terms to the active query. To select multiple terms that do not fall within a continuous range from the index, use the Control key while selecting the terms of interest. Then use the AND, OR, or NOT buttons to add that group of terms to the active query.	Search #5: On the BioSystems search page, click on the Preveiw/Index folder tab, make sure the active query box at the top of the page is clear, then build your search one step at a time: (a) using the text box near the bottom of the page, select the Organism search field and enter the following query: human Then press the "AND" button to move that term/search field selection up to the active query box at the top of the page. (b) again, using the text box near the bottom of the page, select the Title search field and enter the following query: arachidonic acid Press the "AND" button to move that term/search field selection up to the active query box at the top of the page. (c) your query will now appear as: human[Organism] AND arachidonic acid[Title] Press the Preview button at the top of the page if you first want to see the number of documents your query retrieves, or press the Go button to view the records retrieved by your search (as a DocSum search results page). Note that this search will produce the same results as sample searches #4 and #6. It is simply executed in a different way, i.e., you remain on a single query page (Preview/Index) and can browse the index of any search field as you build your query one step at a time.
Complex Boolean	Enter your search in command language, indicating Search Field qualifiers in square brackets [].  (See additional tips for specifying search fields.) Syntax:   term[field] BOOLEAN term[field] BOOLEAN term[field] etc. Boolean operators (AND, OR, NOT) must be written in UPPER CASE. Boolean operators are processed from left to right unless parentheses are used for nesting. If parentheses are used, the portions of the query in parentheses will be processed first, then the remaining Boolean operators will be processed from left to right. Boolean operators can also be used to combine or subtract searches from each other on the History page by entering the search numbers and desired Boolean operators in the query box, for example: #2 AND #3.	Search #6: Simply enter all search terms and search fields as a single statement into the query box: human[Organism] AND arachidonic acid[Title] Note that this search will produce the same results as sample searches #4 and #5, but it takes only a single step when entered directly into the search box as a Boolean query. Search #7: (PTGS1[GeneName] OR "prostaglandin endoperoxide synthase 1"[GeneName]) NOT (primates[Organism] OR rodents[Organism]) This search will retrieve biosystem records that contain PTGS1 or prostaglandin endoperoxide synthase 1 in the GeneName field, but that will not be from any organisms in the taxonomic orders Primata or Rodentia.
Batch Query	Batch Entrez can be used to to upload a text file of GI numbers or accession numbers (one per line) from the Protein database, or to upload a list of record identifiers from other Entrez databases. Once you have retrieved the desired protein sequence records, for example, you can use the "Display" menu at the top of the Entrez Protein search results page to link to the associated BioSystems records. Each retrieved Biosystem record may be associated with one or more of the protein sequences in your original gi number or accession number list.

Additional details about search methods and options are provided in the PubMed help document and Entrez help document.

Search Fields

By default, Entrez searches All Fields of the database unless a specific search field is indicated in the query. Search fields can be selected from pop-up menus on either the Limits and Preview/Index page, or can be typed directly in your query (surrounding field names with square brackets [], for example, [Organism] or [Orgn]).* The Index button on the Preview/Index page allows you to browse the index of each search field, where you can see the available terms, the number of records containing each term or phrase, as well as the syntax for entering values in search fields such as CreateDate or ModifyDate.

The currently available fields include:

Field name	Abbreviation*	Description	Sample Search
All Fields	[ALL]	Searches the complete database record	"arachidonic acid"[all] will retrieve the Biosystems records that contain the phrase "arachidonic acid" in any field of the record. (Compare these search results with those obtained by the sample Title field search, which will retrieve records containing that phrase only in the biosystem title.) The quotes surrounding the search terms ensure they are searched as a phrase.**
Accession	[ACCN]	Searches only the accession number of the biosystem record, which is always an alphanumeric combination (e.g., bsid12345). (If you enter only the digits from the accession (e.g., 12345), use the UID field instead)	bsid82991[accn] will retrieve the biosystem record that contains the specified unique identifier in the accession number field.
CID	[CID]	PubChem Compound identifiers (CIDs) found in a biosystem using the method descibed in the data processing/create direct links/small molecules section of this document.	5280883[cid] will retrieve biosystems that include prostaglandin G2 (PGG2, CID 5280883) as a component.
ChemicalName	[CN]	Names of small molecules that are components in a biosystem. The names include the first four synonyms listed in the PubChem compound records that have been associated with the biosystem through the method described in data processing/create direct links/small molecules. For example, the first four synonyms listed in PubChem CID 5280883 are prostaglandin G2, PGG2, CHEBI:27647, and LMFA03010009; a search for any one of these names will retrieve biosystems that include PGG2 as a component.	PGG2[cn] will retrieve biosystems that include PGG2 as a component.
Comments	[COM]	Comments and additional information provided by the source database on the biosystem
CreateDate	[CDAT] [PDAT] [DP]	The date the biosystem record first appeared in the NCBI biosystems database. This is sometimes referred to as the publication date, hence the synonymous abbreviations PDAT and DP. The syntax for searching the field is YYYY/MM/DD, YYYY/MM, or YYYY. The colon (:) can be used to search for a range of dates, for example, YYYY/MM/DD:YYYY/MM/DD[CDAT].
Description	[DESC]	The text description of a biosystem provided by the source database.
Filter	[FILT]	The "Filter" search field allows you to narrow your retrieval to records that have certain attributes, such as record type (e.g., conserved biosystem or organism specific biosystem). It also allows you to limit search results to biosystem records that have links to other Entrez databases of interest, as shown in the sample search to the right. A detailed explanation of each type of link is provided in the description of an Entrez search results page. The Filter field can also be used to view current database statistics, by entering a search for All[Filt], as shown in the example in the next column.	conserved biosystem[filt] will retrieve only that record type from the BioSystems database. biosystems_structure[filt] will retrieve the BioSystems records that have associated data in the Entrez Structure database. You can then open the "Display" menu near the top of the BioSystems search results page and select Structures to retrieve the corresponding Entrez Structure records (for all biosystems records you have retrieved, or only for those whose checkboxes have been activated). The 3D structure records can then be viewed interactively using the free Cn3D software program. all[filt] will retrieve all of the biosystem database records, showing the total number retrieved.
GeneExternalID	[GEID]	The identifier given to a gene by the source of a biosystem.
GeneID	[GID]	NCBI Entrez Gene IDs found in a biosystem using the method descibed in the data processing/create direct links/genes section of this document. Entrez GeneIDs are numerical identifiers for a genetic locus that remain stable regardless of changes to the locus name, coordinates, or sequence data.	5742[gid] will retrieve biosystems that include the Entrez GeneID 5742 (human PTGS1 gene) as a component.
GeneName	[GN]	Gene name, including all of the synonyms found in the corresponding Entrez Gene record. For example, prostaglandin-endoperoxide synthase 1 (GeneID 5742) has the following synonyms listed in its Entrez Gene record: COX1; COX3; PHS1; PCOX1; PGHS1; PTGHS; PGG/HS; PGHS-1; PTGS1. Any of these synonyms can be searched in the Gene Name field to retrieve biosystems that include the gene as a component.	PTGS1[gn] will retrieve biosystems that include the human PTGS1 gene (Entrez GeneID 5742) as a component.
ModifyDate	[MDAT]	The date the biosystem record last changed in the NCBI biosystems database. The syntax for searching the field is YYYY/MM/DD, YYYY/MM, or YYYY. The colon (:) can be used to search for a range of dates, for example, YYYY/MM/DD:YYYY/MM/DD[MDAT].
Organism	[ORGN]	Organism(s) in which a biosystem is found. A common name (e.g., human), scientific name (e.g., Homo sapiens), or other taxonomic node (e.g, Primates or Primata) can be entered as a query. Note that a search of the organism field will retrieve only organism specific biosystems that fall under the specified taxonomic node. To find corresponding conserved biosystems that are present in numerous organisms, simply follow the "related biosystems/conserved biosystems" link from the biosystem record(s) of interest.	human[orgn] will retrieve biosystems found in human. primates[orgn] will retrieve biosystems found in individual species falling in the order Primata.
ProteinID	[PID]	This field contains the GI numbers and accession numbers of proteins found in a biosystem using the method descibed in the data processing/create direct links/proteins section of this document.	A search for either AAA03630[pid] OR 189887[pid] will retrieve biosystems containing the protein sequence record that has accession number AAA03630 (GI number 189887).
ProteinName	[PN]	Names of proteins in a biosystem. The names are extracted from the definition line of protein sequence records that have been associated with the biosystem using the method descibed in the data processing/create direct links/proteins section of this document.	"prostaglandin endoperoxide synthase 1"[pn] will retrieve biosystems containing a protein component with that name. The quotes surrounding the search terms ensure they are searched as a phrase.**
SID	[SID]	PubChem Substance identifiers (SIDs) found in a biosystem using the method descibed in the data processing/create direct links/small molecules section of this document.
SidExternalID	[SEID]	External registry names for small molecules that are found in a biosystem record, using the method descibed in the data processing/create direct links/small molecules section of this document.
SourceAccession	[SACC]	The accession number assigned to a biosystem by the source database. For example, the NCBI BioSystem record bsid82991, for human arachidonic acid metabolism, is derived from KEGG record hsa00590. Hsa00590 is the source accession.	hsa00590[sacc] will retrieve the KEGG organism specific biosystem for human arachidonic acid metabolism. ko00590[sacc] will retrieve the KEGG conserved biosystem for arachidonic acid metabolism.
SourceID	[SRCID] [SRID]	A numerical identifier that is assigned to a particular source database of biosystem records.	1[srcid] will retrieve records deposited by the BioCyc database. 2[srcid] will retrieve records deposited by the KEGG database.
SourceName	[SRC] [SRCN] [SRNM]	Name of the organization that is the source of the record.	biocyc[src] will retrieve records deposited by the BioCyc database. kegg[src] will retrieve records deposited by the KEGG database.
Title	[TI] [TITL]	Contains the brief title (or name) of the biosystem, for example, "arachidonic acid metabolism", or "citrate cycle", or "TCA cycle", etc. as assigned by the source database.	"arachidonic acid"[ti] will retrieve records with that phrase in the biosystem title. (Compare these search results with those obtained by the sample All Fields search, which will retrieve biosystem records containing that phrase anywhere in the record.) The quotes surrounding the search terms ensure they are searched as a phrase.**
UID	[UID]	Retrieves a biosystem record by its unique identification number, which is the numerical portion of the Accession number. For example, if an accession number is bsid12345, the corresponding UID is 12345. If you enter a string of digits as a query and do not specify a search field, the UID field will be searched by default.	82991[UID] will retrieve the biosystem record whose unique identification number is 82991. 82991 will also retrieve that same biosystem record, because the UID field is searched by default for queries that are only a string of digits.

* In a query, the field name may be typed as the full name or abbreviation, and may be in upper, lower, or mixed case. If more than one abbreviation is shown, any one of them can be used. The field name must be surrounded by square brackets []. A space between the search term and the field specifier is optional. If desired, surround a phrase with quotes to force an adjacency search. For example, the sample queries below will work equally:
      "arachidonic acid"[TI]
      "arachidonic acid"[TITL]
      "arachidonic acid" [TITL]
      "arachidonic acid" [titl]
      "arachidonic acid"[Title]

** The quotes surrounding the query terms in some of the sample searches force the terms to be searched as a phrase. If quotes are not used, the Entrez system may still recognize and handle the terms as a phrase, if they are present in a phrase dictionary used by the search engine. If the terms are not present in the phrase dictionary and are not surrounded by quotes, Entrez will insert a Boolean AND between the terms; in that case, they may or may not appear adjacent to each other in the retrieved records. The "Details" folder tab on a search results page will show you exactly how the Entrez system parsed your query. More search tips are provided in the PubMed help document and Entrez help document.

It is also possible to search for a word stem by using an asterisk (*) as a wild card; for example, arachidon* will retrieve records with terms such as arachidonate, arachidonic, arachidonoyl. The Entrez Help document provides additional information about truncating search terms in this way.

Link from other Entrez Database

The Entrez databases to which biosystems records have been linked (via the data processing pipeline) generally have reciprocal links from their records back to the corresponding NCBI BioSystems database records.

Therefore, if you start your search in an Entrez database other than NCBI BioSystems, you can view the "Links" menus of the records retrieved to see if they have links to associated information in the NCBI BioSystems database. Alternatively, you can use the "Display" menu at the top of an Entrez search results page (in whatever database you have chosen to search) and select "BioSystems" to view the associated biosystem records for all items (default) displayed on the search results page or for those you have selected using their checkboxes.

DocSum (Document Summary) page:  list of records found

The initial search results provide a list (document summary, or "DocSum") of the conserved domain records that contain your search term, which can appear in any field of the record, unless a search field was specified in the query. If desired, you can narrow your search by restricting the query to a search field of interest or adding more terms with a Boolean AND. Alternatively, you can broaden your search by adding more terms (e.g., synonyms) to your query with a Boolean OR, or by following links to Related BioSystems.

Once you are satisfied with your search results, click on the BSID of any record on the DocSum page to view its biosystem summary page. In addition, the following options are available for viewing the search results:

"Show" menu	By default, 20 documents are listed per page. Use the show menu to decrease or increase the number of documents displayed per page.
"Sort by" menu	Search results are displayed in order of decreasing relevance with respect to the query. Many search fields have a score or rank associated with them; for example, the Title and Organism fields have a high rank, while the Comments field has a low rank. The presence of a search term in any one or more of the fields is scored accordingly by the search system, and the total score given to a hit is used in determining its relevance to the query and therefore its placement on the search results page. Currently, the only other sort option is to display by descending or ascending order of modification date. Technical note: If you retrieve all records in the database by searching the Filter field for All[Filt], the records are simply displayed in descending order of BSID.
"Send to" menu	Text - displays the hits shown on the current page as plain text within the browser window. For example, if a search retrieves 23 records and only 10 of them are shown on the current page, the "Send to: Text" option will display those 10 hits as plain text in the browser window. File - saves all the hits retrieved by your search into a plain text file, in whatever display format they are currently shown. For example, if a search retrieves 23 records and they are being displayed in Summary format on the DocSum window, the "Send to: File" option will save all 23 hits in that format into a plain text file, regardless of how many of those hits are being shown per page. Printer - displays the hits shown on the current page in a streamlined HTML format (showing only hits and not the search box, Limits, Preview/Index, History folder tabs, etc.) for easy printing. For example, if a search retrieves 23 records and only 10 of them are shown on the current page, the "Send to: Printer" option will display those 10 hits in the streamlined HTML format withinin the browser window, with an option to print from that page. Clipboard - copies all the hits retrieved by your search (default), or those you have selected by using their checkboxes, into the Clipboard. The Clipboard can temporarily store up to 500 items (they will be lost after 8 hours of inactivity). An asterisk (*) will appear on the Clipboard folder tab to indicate it contains items. You can then click on the "Clipboard" folder tab to view the items in any display format that was available on the original search results page (regardless of the format in which they were displayed when you moved them to the clipboard). For example, if a search retrieves 23 records, the "Send to: Clipboard" option will send all 23 hits (or only those you have selected) into the Clipboard, where you can then view them in any format for up to 8 hours after your last activity in the database. The Clipboard's "Send to" menu, in turn, offers you the same "Text", "File", and "Printer" options as above, a "Clip Remove" option to delete selected items from the Clipboard, and a "My NCBI Collections" option to save all (default) or selected items indefinitely within your My NCBI account.

Additional details about these options are provided in the PubMed help document and Entrez help document.

Display menu options

The "Display" menu on the DocSum (search results) page allows you to view output in the formats below. It also allows you to retrieve other types of data associated with the biosystem(s) records of interest. The "Display" menu options act upon all of the biosystem records in the current window (default) or on the subset selected with checkboxes.

Display Option Type	Option Name	Description
BioSystem record formats *	Summary *	shows the following information for a biosystem, as available: BSID links (pop-up menus) appear to the right of the BSID and provide access to related data within the BioSystems database and in other Entrez databases. biosystem title (biosystem name) record type (organism specific biosystem or conserved biosystem) The first 250 characters of the description, if one has been provided by the source database organism in which the biosystem is found (no organism name is displayed for conserved biosystems) source database and corresponding source accession
	Brief *	This format is similar to Summary format, above, with the exception that it does not display biosystem descriptions.
	UI List *	shows only the following information for each biosystem: BSID links (pop-up menus) appear to the right of the BSID and provide access to related data within the BioSystems database and in other Entrez databases.
	Abstract *	This format is similar to Summary format, above, with the exception that it displays the complete biosystem descriptions, rather than only the first 250 characters.
Retrieve biosystem components	Genes Nucleotides Proteins Structures PubChem Compounds PubChem Substances	Retrieve components for all the biosystem records listed in the current window (default) or for those you have selected with checkboxes. The data sets retrieved by each option are described in the "Links to Related Data" section of this document.	Note: These display menu options are similar in function to the links (pop-up menus) shown beside each record in a search results page. The only difference is that the Display menu options can act upon multiple biosystem records (all records in the current window (default) or those selected with checkboxes), whereas the Links pop-up menu options act only upon the single biosystem beside which they are listed.
Retrieve literature describing the biosystem	PubMed OMIM	Retrieve articles cited by the source database in a biosystem record as well as OMIM entries associated with genes involved in the biosystem. The data sets retrieved by each option are described in the "Links to Related Data" section of this document.
Retrieve related biosystems	Organism Specific BioSystems Conserved BioSystems Linked BioSystems Similar BioSystems Superset BioSystems Subset BioSystems	Retrieve related biosystems for all the records listed in the current window (default) or for those you have selected with checkboxes. The data sets retrieved by each option are described in the "Links to Related Data" section of this document.
Retrieve associated data from other databases	Conserved Domains HomoloGene ProteinClusters Taxonomy	Retrieve data from other Entrez databases that are associated with all the biosystem records listed in the current window (default), or with those you have selected with checkboxes. The data sets retrieved by each option are described in the "Links to Related Data" section of this document.

* The variation in BioSystem record formats on the DocSum (search results) page is most evident for biosystems that have descriptions, such as the records retrieved by a search for human TCA cycle. If a search retrieves primarily biosystems for which descriptions are not available, the various BioSystem record formats might appear very similar to each other. In all cases, click on the BSID or title of a hit to view its BioSystem record.

Links to related data

As noted in the page on discovering associations among previously disparate data, the Entrez retrieval system is designed to provide integrated access to previously disparate data and make it possible to collect related information on a topic of interest within and across Entrez databases. As part of Entrez, the NCBI BioSystems database implements a data processing pipeline to identify such associations and present them as a series of Links pop-up menus on DocSum (search results) pages. The pop-up menus are described below and also appear on individual BioSystem records.

Some of the data accessible through these Links menus are also presented in folder tabs on the individual BioSystem records. Some of the folder tabs present the data in a different way (e.g., sort identical proteins by PIG ID in the Proteins folder tab) and/or provide additional functions (e.g., the ability to highlight selected components in the source database's full size diagram). In addition, other small differences may exist, as noted in the descriptions of the Genes and Citations folder tabs.

Link Group	Link Name	Description
Related BioSystems	Organism Specific BioSystems	The organism specific biosystems that correspond to a conserved biosystem, as determined by the source database.
	Conserved BioSystems	The conserved biosystem, if one is available, that corresponds to an organism specific biosystem. Conserved biosystems are canonical biosystems that are used to group together orthologous, organism specific biosystems, and are derived from "reference pathways" in the KEGG database.
	Linked BioSystems	Biosystems that the source database has explicitly stated are connected in some way.
	Similar BioSystems	Biosystems share at least one identical protein sequence from the same source organism. In other words, the shared protein is in the same protein identity group (PIG) and has the same Taxonomy ID (TaxID).
	Superset BioSystems	Biosystems that are one node above the one currently being viewed, according to a hierarchical organization used by the source database. For example, "Phase 1 - Functionalization of compounds" (bsid105699) is a superset of "COX reactions" (bsid105711), reflecting the hierarchical organization of those biosystems specified by the source database, Reactome.
	Subset BioSystems	Biosystems that are one node below the one currently being viewed, according to a hierarchical organization used by the source database. For example, "COX reactions" (bsid105711) are a subset of "Phase 1 - Functionalization of compounds" (bsid105699), reflecting the hierarchical organization of those biosystems specified by the source database, Reactome.
Literature	PubMed Citations	PubMed records whose PMIDs were explicitly cited in (and extracted from) the source database record.
	OMIM	Records from the Online Mendelian Inheritance in Man (OMIM) database that are linked to the Entrez Gene records which in turn have been associated with a BioSystem during data processing.
Sequences	Genes	Entrez Gene records that have been associated with a biosystem using the method descibed in the data processing/create direct links/genes section of this document.
	Proteins	Entrez Protein records that have been associated with a biosystem using the method descibed in the data processing/create direct links/proteins section of this document.
	Conserved Domains	Conserved domains that are specific hits to the proteins that have been associated with a BioSystem via the method descibed in data processing/create direct links/proteins.
	HomoloGene	Proteins that have been associated with a BioSystem (via the method descibed in data processing/create direct links/proteins) might have links to the HomoloGene database. If they do, then the biosystem record is linked to those HomoloGene records as well.
	ProteinClusters	Proteins that have been associated with a BioSystem (via the method descibed in data processing/create direct links/proteins) might have links to the Protein Clusters database. If they do, then the biosystem record is linked to those Protein Cluster records as well.
Small Molecules	PubChem Compounds	PubChem Compound records that have been associated with a biosystem using the method descibed in the data processing/create direct links/small molecules section of this document.
	PubChem Substances	PubChem Substance records that have been associated with a biosystem using the method descibed in the data processing/create direct links/small molecules section of this document.
Other Links	BioAssays via Actives	PubChem Compound records that have been associated with a biosystem (via the method descibed in the data processing/create direct links/small molecules) might have links to the PubChem BioAssay database. If they do, the BioAssays via Actives link retrieves the subset of bioassay records in which those compounds have been found to be active. Note:  If you would like to see whether a specific compound (CID) has been found to be active in a bioassay record, click on the CID of interest in the small molecules folder tab of a biosystem record to view the corresponding PubChem Compound record and see the various "Links" available for that record.
	BioAssays via Target	Proteins that have been associated with a BioSystem (via the method descibed in data processing/create direct links/proteins) might have their GI numbers cited as targets in PubChem BioAssay records. If they do, the BioAssays via Target link retrieves the subset of bioassay records in which those proteins are targets of an assay. Note:  If you would like to see whether a specific protein has been used as the target of a bioassay, click on the GI number of interest in the proteins folder tab of a biosystem record to view the corresponding protein sequence record and see the various "Links" available. If the protein's GI number is named as a target in a BioAssay record, the Links menu in the protein sequence record will include an option for "BioAssay by Target". If that GI was not specifically named as a target but an identical protein sequence (belonging to the same PIG) was, the Links menu will include an option for "BioAssay by Target, identical sequence."
	Structures	If proteins that have been associated with a BioSystem (via the method descibed in data processing/create direct links/proteins) are derived from 3D structure records, then the biosystem record is linked to those structure records as well. The 3D protein structures can be viewed with Cn3D, a free helper application available for Windows, Macintosh, and Unix platforms; a tutorial describes the program's features and functions. Note:  If you would like to see whether a specific protein in a biosystem has a resolved 3D structure, click on the GI number of interest in the proteins folder tab of a biosystem record to view the corresponding sequence record in the Entrez Protein database. The "Links" menu in the protein sequence record will indicate whether a 3D structure is available, and what type of association exists between the sequence and structure: an option for "Structure" will appear in the Links menu if the protein was derived directly from a 3D structure record an option for "Related Structure" will appear in the Links menu if similar protein sequences, identified via BLAST, were derived from 3D structures (The "Other Links:Structures" option in a BioSystem record retrieves the former subset of structures but not the latter.)
	Taxonomy	This link retrieves the NCBI Taxonomy database record for the source organism whose Taxonomy ID (TaxID) was provided in the source record. For additional information, see the data processing/create direct links/taxonomy section of this document.

View details for an individual BioSystems record

Regardless of the format in which you have chosen to display your search results, simply click on the BSID or biosystem title for a record of interest to view its BioSystem record.

BIOSYSTEM RECORD COMPONENTS AND FEATURES   BSID and Links to related data Descriptive information BioSystem Title (name) Record Type BioSystem Description Organism Source database and corresponding source accession Thumbnail Diagram Folder Tabs that categorize and list biosystem components and associated data Genes Proteins Small Molecules Related BioSystems Organism Specific BioSystems Conserved BioSystems Linked BioSystems Similar BioSystems Superset BioSystems Subset BioSystems Citations Comments Highlight selected records (genes, proteins, small molecules) in full size biosystem diagram at source database Save biosystem component lists Save copy of archival biosystem record (ASN.1, XML, or JSON format)   BSID and Links to related data BSID:  This BSID is the accession number or unique identifier of the biosystem record; it is always an alphanumeric combination (e.g., BSID82291, for human arachidonic acid metabolism). Links to related data:  The pop-up menus that appear in the upper right corner of a biosystem record allow you to retrieve related biosystems, literature, biosystem components such as genes, sequences, and small molecules, and more. These pop-up menus also appear on DocSum (search results) pages and are explained in detail in that section of the help document, under links to related data.

SAMPLE BIOSYSTEM RECORD

Descriptive Information

Title:  The brief title (or name) of the biosystem, for example, "arachidonic acid metabolism", or "citrate cycle", or "TCA cycle", etc. as assigned by the source database.

Type:  Record type (organism specific biosystem or conserved biosystem).

Description:  The text description of a biosystem provided by the source database. Some biosystem records have a description (e.g., bsid82927, human TCA cycle) and others do not (e.g., bsid82991, human arachidonic acid metabolism).

Organism:  The source organism in which a biosystem is found. The organism name, whose Taxonomy ID (TaxID) was provided in the source record, links to the corresponding record in the NCBI Taxonomy database. For additional information, see the data processing/create direct links/taxonomy section of this document.

Source database and corresponding source accession number:  The name of the source database that deposited the record into the NCBI BioSystems database, and the local accession number assigned to that record by the source database. For example, the NCBI BioSystem record bsid82991, for human arachidonic acid metabolism, is derived from KEGG record hsa00590 (see illustration).

Thumbnail Diagram

Thumbnail Image Provided by Source Database	If a thumbnail image of a biosystem diagram has been provided by a source database, the image is placed in the corresponding BioSystems database record and links to a full-size image that resides on the source database web site. At present, thumbnail images as well as the ability to highlight selected components (genes, proteins, small molecules) in a full size image of the biosystem diagram are currently available only for KEGG records.
Thumbnail Image Not Available	If a thumbnail image of a biosystem diagram has not been provided by a source database, a full size diagram may be available at the source database by following the link in the BioSystem record for the source's accession number.
Independent of the availability of a thumbnail image, each BioSystem record lists and categorizes the biosystem components, as noted below, in order to facilitate computation on biosystems data, and provides links to related data throughout the Entrez system.

Folder Tabs that categorize and list biosystem components and associated data

The folder tabs (illustration) near the bottom of a biosystems record categorize and list biosystem components and associated data. A pagination function at the bottom of each folder tab allows you to browse through the complete list of components in any category.

You can select items on multiple pages within a folder tab (for example, item 3 on page 1 and item 12 on page 2). The selections will persist as you browse within and across folder tabs until you clear the selections in a given tab. However, the Highlight selected records function will work for one folder tab at a time -- the active folder tab.

The "Click to view and/or save records in Entrez [DatabaseName]" allows you to view all (default) or selected records in the database where they reside. Additional notes are provided below on how to save biosystem component lists and save an archival copy of a biosystem record.

The data displayed by the folder tabs are also accessible via the links to related data pop-up menus that appear in the upper right corner of a biosystem record and on DocSum (search results) pages, with the exceptions noted below (e.g., Genes and Citations folder tabs). In addition, some of the folder tabs present the data in a different way (e.g., sort identical proteins by PIG ID in the Proteins folder tab) and/or provide additional functions (e.g., highlight selected components in the source database's full size diagram). Conversely, the pop-up menus offer links to some data types (e.g., 3D protein structures, biological activity data for small molecules) not presented in the folder tabs; those menus are explained in detail in the links to related data section of the help document.

Folder Tab	Description and Comments
Genes	Genes that have been associated with a biosystem using the method descibed in the data processing/create direct links/genes section of this document. Clicking on a GeneID will open the corresponding record in the Entrez Gene database. If the source record did not specify a GeneID, only the gene name that was specified by the source database in the original record will be displayed and no link to the Entrez Gene database is available. Genes that are shown only by name are visible in the Genes folder tab but are not retrieved by the "Sequences:Genes" pop-up links menu in the upper right corner of the biosystem record.
Proteins	Proteins that have been associated with a biosystem using the method descibed in the data processing/create direct links/proteins section of this document. Proteins that belong to the same protein identity group (PIG) -- that is, proteins that have identical sequence length and composition -- are grouped together because this folder tab sorts the proteins by PIG ID.
Small Molecules	PubChem Compounds and PubChem Substances that have been associated with a biosystem using the method descibed in the data processing/create direct links/small molecules section of this document.
Related BioSystems	Other biosystem records that are related to the record you are viewing:
Organism Specific BioSystems	The organism specific biosystems that correspond, as determined by the source database, to the conserved biosystem currently being viewed.
Conserved BioSystems	The conserved biosystem, if one is available, that corresponds to the organism specific biosystem currently being viewed. Conserved biosystems are canonical biosystems that are used to group together orthologous, organism specific biosystems, and are derived from "reference pathways" in the KEGG database.
Linked BioSystems	Biosystems that the source database has explicitly stated are connected in some way.
Similar BioSystems	Biosystems share at least one identical protein sequence from the same source organism. In other words, the shared protein is in the same protein identity group (PIG) and has the same Taxonomy ID (TaxID).
Superset BioSystems	Biosystems that are one node above the one currently being viewed, according to a hierarchical organization used by the source database. For example, "Phase 1 - Functionalization of compounds" (bsid105699) is a superset of "COX reactions" (bsid105711), reflecting the hierarchical organization of those biosystems specified by the source database, Reactome.
Subset BioSystems	Biosystems that are one node below the one currently being viewed, according to a hierarchical organization used by the source database. For example, "COX reactions" (bsid105711) are a subset of "Phase 1 - Functionalization of compounds" (bsid105699), reflecting the hierarchical organization of those biosystems specified by the source database, Reactome.
Citations	PubMed records whose PMIDs were explicitly cited in (and extracted from) the source database record. If the source record contains a text citation but no PMID, the citation is displayed in the folder tab, but no link to PubMed is provided and those articles are not retrieved by the "Literature:PubMed" pop-up links menu in the upper right corner of the biosystem record.
Comments	Comments and additional information provided by the source database on the biosystem.

Highlight selected records (genes, proteins, small molecules) in full size biosystem diagram at source database

If a source database provides a function to highlight selected biosystem components in the full size diagram on their web site (as KEGG currently does for genes and small molecules), the folder tab for that component type will display an option to "Highlight Selected Records in Source Database." That allows you to see where in a biosystem your gene(s), protein(s), or small molecule(s) of interest occur. There are two ways to do this: (a) by using check boxes in folder tabs or (b) by writing a specially formatted URL: (a) Check boxes in folder tabs: To select specific genes, proteins, or small molecules while viewing a biosystem record, simply activate the check boxes for the component(s) of interest. The pagination function at the bottom of a folder tab allows you to select items on multiple pages within the tab. Then use the "Highlight Selected Records" option to open the full size biosystem diagram on the source database's web site. The components you selected will be displayed with a red outline. Note, however, that the highlight function works for one folder tab at a time -- the active folder tab. For example, the PTGS1 gene (GeneID 5742) is included in the BioSystems component list for the human arachidonic acid metabolism pathway (bsid82991). If you activate the checkbox for GeneID 5742 in the "Genes" folder tab of the record, then use the option to "Highlight Selected Records in Source Database", the gene will be highlighted with a red outline in the corresponding KEGG record for Arachidonic Acid Metabolism, as shown in the illustration to the right. (In that view, the PTGS1 gene product is displayed as Enzyme Commission (EC) number 1.14.99.1.)

HIGHLIGHT SELECTED BIOSYSTEM COMPONENTS

Save biosystem component lists

Biosystem component lists can be saved by following the "Click to view and/or save record in Entrez [DatabaseName]" link in the folder tab of the desired component type. Doing this will retrieve the genes/proteins/small molecules that were explicitly listed by the source database in their original biosystem record, plus additional genes/proteins/small molecules that have been associated with the biosystem by the NCBI data processing procedure.

Once you are viewing the components in the relevant Entrez database, you can display and/or save those records in any format that is available for that database. For example, records from the Entrez Protein database can be saved in FASTA format (which is convenient for sequence analysis), as a list of GI numbers, or in other formats such as GenPept (which contains sequence data plus annotations, similar to GenBank format). The Entrez help document provides additional information about sequence database record formats. The Entrez Gene help and PubChem help documents describe record formats for genes and small molecules, respectively.

Save copy of archival biosystem record

The ASN.1, XML, and JSON buttons near the bottom of a biosystem record save an archival copy of the biosystem record that reflects the content deposited by the source database. This includes only the genes/proteins/small molecules that were explicitly listed by the source database in their deposited record, and not the additional genes/proteins/small molecules that were associated with the biosystem record via NCBI data processing. The archival record also includes the additional content that was present in the deposited record, such as annotations about the biosystem.

Citing the NCBI BioSystems Database:

Geer LY, Marchler-Bauer A, Geer RC, Han L, He J, He S, Liu C, Shi W, Bryant SH. The NCBI BioSystems database. Nucleic Acids Res. 2009 Oct 23 [Epub 2009 ahead of print] [Full Text] [PDF]

Articles Describing Source Databases:

The articles below are provided for your convenience if you would like more information on any source database. Please consult the web site of a source database for information on how to cite it and for additional articles.

	BioCyc -- Caspi R, Foerster H, Fulcher CA, Kaipa P, Krummenacker M, Latendresse M, Paley S, Rhee SY, Shearer AG, Tissier C, Walk TC, Zhang P, Karp PD. The MetaCyc Database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases. Nucleic Acids Res. 2008 Jan; 36(Database issue): D623-31.  [PubMed] [Full Text] [Database Website: http://biocyc.org/]
	EcoCyc -- Keseler IM, Bonavides-Martínez C, Collado-Vides J, Gama-Castro S, Gunsalus RP, Johnson DA, Krummenacker M, Nolan LM, Paley S, Paulsen IT, Peralta-Gil M, Santos-Zavaleta A, Shearer AG, Karp PD. EcoCyc: a comprehensive view of Escherichia coli biology. Nucleic Acids Res. 2009 Jan; 37(Database issue): D464-70.  [PubMed] [Full Text] [Database Website: http://ecocyc.org/]
	KEGG -- Kanehisa M, Araki M, Goto S, Hattori M, Hirakawa M, Itoh M, Katayama T, Kawashima S, Okuda S, Tokimatsu T, Yamanishi Y. KEGG for linking genomes to life and the environment. Nucleic Acids Res. 2008 Jan; 36(Database issue): D480-4.  [PubMed] [Full Text] [Database Website: http://www.genome.jp/kegg/]
	Reactome -- Matthews L, Gopinath G, Gillespie M, Caudy M, Croft D, de Bono B, Garapati P, Hemish J, Hermjakob H, Jassal B, Kanapin A, Lewis S, Mahajan S, May B, Schmidt E, Vastrik I, Wu G, Birney E, Stein L, D'Eustachio P. Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Res. 2009 Jan; 37(Database issue): D619-22.  [PubMed] [Full Text] [Database Website: http://www.reactome.org/]
	Reactome -- Vastrik I, D'Eustachio P, Schmidt E, Gopinath G, Croft D, de Bono B, Gillespie M, Jassal B, Lewis S, Matthews L, Wu G, Birney E, Stein L. Reactome: a knowledge base of biologic pathways and processes Genome Biology 2007 Mar; 8(3):R39.  [PubMed] [Full Text] [Database Website: http://www.reactome.org/]