Database system employing protein function hierarchies for viewing biomolecular sequence data

• US 6,023,659 A
• Filed: 03/06/1997
• Issued: 02/08/2000
• Est. Priority Date: 10/10/1996
• Status: Expired due to Fees

• Current Assignee: Incyte Genomics, Inc. (Incyte Corporation)
• Original Assignee: Incyte Pharmaceuticals, Inc. (Incyte Corporation)
• Inventors: Hillman, Jennifer L., Russo, Frank, Akerblom, Ingrid E., Au-Young, Janice, Seilhamer, Jeffrey J., Klingler, Tod M., Maslyn, Timothy J., Altus, Christina M.
• Primary Examiner(s): Kemper, Melanie A.
• Application Number:
  US08/812,290
• Time in Patent Office: 1,069 Days
• Field of Search: 364/496, 364/498, 395/606, 435/6, 702/19, 702/20, 702/27, 702/31, 702/32, 702/3, 702/7, 702/100, 702/205
• US Class Current: 702/19
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics

Abstract

Disclosed is a relational database system for storing biomolecular sequence information in a manner that allows sequences to be catalogued and searched according to one or more protein function hierarchies. The hierarchies allow searches for sequences based upon a protein'"'"'s biological function or molecular function. Also disclosed is a mechanism for automatically grouping new sequences into protein function hierarchies. This mechanism uses descriptive information obtained from "external hits" which are matches of stored sequences against gene sequences stored in an external database such as GenBank. The descriptive information provided with the external database is evaluated according to a specific algorithm and used to automatically group the external hits (or the sequences associated with the hits) in the categories. Ultimately, the biomolecular sequences stored in databases of this invention are provided with both descriptive information from the external hit and category information from a relevant hierarchy or hierarchies.

Claims

1. A computer system comprising:

a database containing records pertaining to a plurality of biomolecular sequences;

a first hierarchy of protein function categories into which at least some of said biomolecular sequences are grouped, said protein function categories specifying biological functions of proteins corresponding to said biomolecular sequences and said first hierarchy including

(i) a first set of protein function categories specifying biological functions at a cellular level, and

(ii) a second set of protein function categories specifying biological functions at a level above the cellular level; and

a user interface allowing a user to selectively view information regarding said plurality of said biomolecular sequences as it relates to said first hierarchy.

2. The computer system of claim 1, wherein the biomolecular sequences include nucleic acids.

3. The computer system of claim 2, wherein the biomolecular sequences are selected from the group consisting of ESTs, full-length sequences, and combinations thereof.

4. The computer system of claim 1, wherein the biomolecular sequences include amino acid sequences.

5. The computer system of claim 1, wherein the records include descriptive information from an external database, which information correlates said biomolecular sequences to records in said external database.

6. The computer system of claim 5, wherein the external database is GenBank.

7. The computer system of claim 1, wherein the second set of protein function categories specifies biological functions at an organism level or a tissue level.

8. The computer system of claim 1, further comprising a second hierarchy of protein function categories into which at least some of said biomolecular sequences are grouped, said second hierarchy specifying at least one of (i) molecular functions of proteins corresponding to said biomolecular sequences and (ii) enzymatic functions of proteins corresponding to said biomolecular sequences.

9. The computer system of claim 8, wherein the second hierarchy is an enzyme list provided by the Enzyme Commission.

10. The computer system of claim 8, wherein the user interface allows the user to selectively view information regarding a subset of said plurality of said biomolecular sequences which subset is grouped in both a selected category from the first hierarchy and a selected category from the second hierarchy.

11. The computer system of claim 1, wherein the user interface allows the user to view biomolecular sequence records associated with a category selected from the first hierarchy.

12. The computer system of claim 1, wherein the user interface allows the user to view categories from the first hierarchy that are associated with a selected biomolecular sequence record.

13. The computer system of claim 1, wherein at least some of said biomolecular sequences are provided as part of one or more projects for obtaining full-length gene sequences from shorter sequences, and wherein the database records contain information about said one or more projects.

14. A method of using a computer system to present information pertaining to a plurality of biomolecular sequence records stored in a database, the method comprising:

displaying a list of said records or a field for entering information identifying one or more of said records;

identifying one or more of said records that a user has selected from said list or field;

matching said one or more selected records with one or more protein function categories from a first hierarchy of protein function categories into which at least some of said biomolecular sequence records are grouped; and

displaying the one or more categories matching said one or more selected records, wherein said protein function categories specify biological functions of proteins corresponding to said biomolecular sequences and said first hierarchy includes

(i) a first set of protein function categories specifying biological functions at a cellular level, and

(ii) a second set of protein function categories specifying biological functions at a tissue level.

15. The method of claim 14, wherein biomolecular sequences include nucleic acid sequence, amino acid sequences, or both nucleic acid sequences and amino acid sequences.

16. The method of claim 14, wherein the first hierarchy includes a third set of protein function categories specifying biological functions at an organism level.

17. The method of claim 14, further comprising

matching said one or more selected records with one or more protein function categories from a second hierarchy of protein function categories into which at least some of said biomolecular sequences are grouped;

and

displaying the one or more categories from the second hierarchy matching said one or more selected records, wherein said protein function categories from the second hierarchy specify at least one of (i) molecular functions of proteins corresponding to said biomolecular sequences and (ii) enzymatic functions of proteins corresponding to said biomolecular sequences.

18. The method of claim 14, wherein the list of records includes a field of descriptive information from an external database containing sequence records corresponding to the records in the list of records.

19. The method of claim 18, wherein the step of identifying one or more of said records includes determining that the user has selected the descriptive information for the one or more records.

20. The method of claim 14, wherein at least some of said biomolecular sequences are provided as part of one or more projects for obtaining full-length gene sequences from shorter sequences, and wherein the database records contain information about said one or more projects.

21. A method of using a computer system to present information pertaining to a plurality of biomolecular sequence records stored in a database, the method comprising:

displaying a list of one or more protein biological function categories from a first hierarchy of protein biological function categories into which at least some of said biomolecular sequence records are grouped

identifying one or more of said protein biological function categories that a user has selected from said list;

matching said one or more selected protein biological function categories with one or more biomolecular sequence records which are grouped in the selected protein biological function categories; and

displaying the one or more sequence records matching said one or more selected protein biological function categories, wherein said protein biological function categories specify biological functions of proteins corresponding to said biomolecular sequences and said first hierarchy includes

(i) a first set of protein biological function categories specifying biological functions at a cellular level, and

(ii) a second set of protein biological function categories specifying biological functions at a tissue level.

22. The method of claim 21, wherein biomolecular sequences include nucleic acid sequence, amino acid sequences, or both nucleic acid sequences and amino acid sequences.

23. The method of claim 21, wherein the first hierarchy includes a third set of protein biological function categories specifying biological functions at an organism level.

24. The method of claim 21, further comprising

displaying a second list of one or more protein molecular function categories from a second hierarchy of protein function categories into which at least some of said biomolecular sequence records are grouped

identifying one or more of said protein molecular function categories that a user has selected from said second list;

matching said one or more selected protein molecular function categories with one or more biomolecular sequence records which are grouped with in selected protein molecular function categories; and

displaying the one or more sequence records matching both the one or more selected protein biological function categories and the one or more protein molecular function categories, wherein said protein molecular function categories from the second hierarchy specify at least one of (i) general molecular functions of proteins corresponding to said biomolecular sequences and (ii) enzymatic functions of proteins corresponding to said biomolecular sequences.

25. The method of claim 21, further comprising

determining that the user has elected to merge the selected protein biological function categories with other categories from the hierarchy, which other categories are related to the selected protein biological function categories;

and

performing said step of matching with both said other categories and said selected protein biological function categories.

26. The method of claim 21, wherein at least some of said biomolecular sequences are provided as part of one or more projects for obtaining full-length gene sequences from shorter sequences, and wherein the database records contain information about said one or more projects.

27. A database system having a plurality of internal records, the database comprising:

a plurality of sequence records specifying biomolecular sequences, at least some of said records referencing hits to an external database, which hits specify genes having sequences that at least partially match those of the biomolecular sequences

a plurality of external hit records specifying said hits to said external database, at least some of said records referencing protein function hierarchy categories which specify at least one of biological functions of proteins or molecular functions of proteins.

28. The database of claim 27, wherein at least some of said plurality of sequence records reference biomolecular sequences belonging to one or more projects for obtaining full-length gene sequences from shorter sequence.

29. The database of claim 28, wherein the sequence records specify a sequence type which characterized the sequence according to its role in a project.

30. The database of claim 29, wherein the sequence type can be at least (i) a full-length sequence corresponding to a complete gene sequence, (ii) a 5'"'"' complete sequence containing a sequence to the 5'"'"' terminus of a gene, and (iii) a first pass sequence containing the first sequence information provided to the project.

31. The database of claim 27, wherein the external database is GenBank.

32. The database of claim 27, wherein the sequence records include descriptive information derived from said external database and pertaining to said hit.

33. The database of claim 27, wherein the biomolecular records specified by the sequence records can be amino acid sequences or nucleic acid sequences.

34. The database of claim 27, wherein the protein function hierarchy includes

(i) a first set of protein function categories specifying biological functions at a cellular level, and

(ii) a second set of protein function categories specifying biological functions at a level above the cellular level.

35. In an internal database, a method of using a computer system to automatically categorize biomolecular sequence records into protein function categories, the method comprising the steps of:

(a) receiving descriptive information about a biomolecular sequence in the internal database from a record in an external database, which record pertains to a gene having a sequence that at least partially matches that of the biomolecular sequence;

(b) determining whether the descriptive information contains one or more terms matching one or more keywords associated with a first protein function category, the keywords being terms consistent with a classification in the first protein function category;

(c) when at least one keyword is found to match a term in the descriptive information, determining whether the descriptive information contains a term matching one or more anti-keywords associated with the first protein function category, the anti-keywords being terms inconsistent with a classification in the first protein function category;

(d) grouping said biomolecular sequence in the first protein function category when the descriptive information contains a term matching a keyword but contains no term matching an anti-keyword.

36. The method of claim 35, further comprising a step of BLASTing the biomolecular sequence against genes in the external database to identify the record in an external database which pertains to a gene having a sequence that at least partially matches that of the biomolecular sequence.

37. The method of claim 35, wherein the external database is GenBank.

38. The method of claim 37, wherein the descriptive information is obtained from a definition section of the record in an external database, a keyword section of the record in the external database, or a combination of the definition section and the keyword section.

39. The method of claim 35, further comprising a step of filtering said descriptive information prior to step (a) to standardize terminology.

40. The method of claim 35, wherein step (c) includes the following steps:

determining whether the descriptive information contains a term matching one or more global anti-keywords associated with the first protein function category; and

determining whether the descriptive information contains a term matching one or more local anti-keywords associated with the first protein function category, each local anti-keyword being used only in association with a specified keyword.

41. The method of claim 35, wherein steps (b) through (d) are repeated but with a second protein function category substituted for said first protein function category.

42. A computer readable medium including program instructions for performing the following steps:

(a) receiving descriptive information about a biomolecular sequence in the internal database from a record in an external database, which record pertains to a gene having a sequence that at least partially matches that of the biomolecular sequence;

(b) determining whether the descriptive information contains one or more terms matching one or more keywords associated with a first protein function category, the keywords being terms consistent with a classification in the first protein function category;

(c) when at least one keyword is found to match a term in the descriptive information, determining whether the descriptive information contains a term matching one or more anti-keywords associated with the first protein function category, the anti-keywords being terms inconsistent with a classification in the first protein function category;

(d) grouping said biomolecular sequence in the first protein function category when the descriptive information contains a term matching a keyword but contains no term matching an anti-keyword.

43. The computer readable medium of claim 42, further comprising program instructions for performing a step of filtering said descriptive information prior to step (a) to standardize terminology.

44. The computer readable medium of claim 42, wherein the program instructions for performing step(c) include instructions for

determining whether the descriptive information contains a term matching one or more global anti-keywords associated with the first protein function category;

and

determining whether the descriptive information contains a term matching one or more local anti-keywords associated with the first protein function category, each local anti-keyword being used only in association with a specified keyword.

45. The computer readable medium of claim 42, further comprising program instructions for repeating steps (b) through (d) with a second protein function category substituted for said first protein function category.