Bioinformatic Databases

1. Bioinformatic Databases Norie de la Cruz, PhD

2. Take home The internet is a powerful resource containing a large volume of data and tools to manipulate them� unfortunately, connecting data between them can sometimes be tricky.

3. Overview Whirlwind tour of Web databases The Rat Genome Database � data, tools, and operations

4. Bioinformatic databases on the WWW Loose definition of database here Vary widely in terms of offerings, data, tools and specialization Vary widely in terms of data collection methodologies

5. Some classifications per NAR Major sequence repositories Gene Expression Comparative genomics Gene Identification and Structure Genetic and physical maps Genomic Databases Intermolecular interactions Metabolic Pathways and Cellular Regulation Mutation Databases Pathology

6. Some classifications per NAR Protein Databases Protein sequence Motifs Proteome Resources Retrieval systems RNA Sequences Structure Transgenics Varied Biomedical Content

7. Major Sequence Repositories GenBank RefSeq DDBJ Ensemble Unigene Collection of sequence data Genomic Markers Genes Proteins Some provide tools to expedite access Blast Search Alignment tools Translation tools etc. Varying degrees of quality control Machine data upload Human curation and QC

8. Major Sequence Repositories: Genbank All know nucleotide and protein sequences Provides submission system for various authors Little QC

9. Major Sequence Repositories: RefSeq Non redundant collection of naturally occurring biological molecules Human QC Comprehensive, integrated set of sequences for major research organisms Provides a stable reference for further characterization of sequences including comparative analyses, mutations, expression, etc.

10. Major Sequence Repositories: Unigene Attempts to cluster GenBank sequences into gene-oriented clusters Each cluster contains sequences that represent one gene Provides a stable reference for further characterization of sequences including comparative analyses, mutations, expression, etc.

11. Major Sequence Repositories: DDBJ (DNA Data Bank of Japan) Japanese equivalent to NCBI efforts Attempting to gather all known nucleotide and protein sequences Part of the International Nucleotide Sequence Collaboration

12. Major Sequence Repositories: EMBL Nucleotide Sequence Database European equivalent to NCBI efforts Attempting to gather all known nucleotide and protein sequences Part of the International Nucleotide Sequence Collaboration

13. Major Sequence Repositories: UCSC Genome Browser Visual representation of genome and sequence data Run by University of California at Santa Cruz

14. Comparative Genomics

15. Comparative Genomics:  Microbial Genome Database for Comparative Analysis

16. Comparative Genomics:  Some specialized sites

17. Comparative Genomics:  Clusters of Orthologous Groups Phylogenetic classification of the proteins encoded in complete genomes Proteins grouped according to sequence by a program called COGNITOR Must be represented in at least three species in a group of 43 species representing phylogenetic lineages Each COG consists of individual proteins or groups of paralogs from at least 3 lineages and thus corresponds to an ancient conserved domain.

18. Gene Expression

19. Gene Expression: Array Express

20. Gene Expression: Edinburgh Mouse Atlas Project

21. Gene Expression: HugeIndex (Human Gene Expression Index)

22. Gene Expression: Other specialized sites

23. Gene Identification and Structure

24. Gene Identification and Structure:SNP Consortium database

25. Gene Identification and Structure:Alternative Splicing Annotation Project (ASAP)

26. Gene Identification and Structure:PromEC

27. Gene Identification and Structure:Some other specialized sites

28. Genetic and physical maps Repository for marker information Data on gene locations within the genome Map of cloned sequences Tools to integrate information across genomes

29. Genetic and Physical Maps:HuGeMap

30. Genetic and Physical Maps:GeneMap�99

31. Genomic Databases Data repositories for research results on various model organisms Rat Human Fruit fly Worm Arabidopsis Some other rodent Linking information across databases Tools to organize and integrate information

32. Genomic Databases:The Rat Genome Database

33. Genomic Databases:FlyBase

34. Genomic Databases:EcoGene

35. Genomic Databases:Some other examples

36. Mutation Databases Allele distributions in populations Inherited genetics diseases Mutations in proteins implicated in disease development

37. Mutation Databases: ALFRED designed to make allele frequency data on anthropologically defined human population samples readily available to the scientific community link these polymorphism data to the molecular genetics-human genome databases

38. Mutation Databases: Human Gene Mutation Database an attempt to collate known (published) gene lesions responsible for human inherited disease provides information of practical diagnostic importance to researchers and diagnosticians in human molecular genetics physicians interested in a particular inherited condition in a given patient or family genetic counsellors.

39. Mutation Databases:Online Mendelian Inheritance in Man (OMIM) catalog of human genes and genetic disorders contains textual information, pictures, and reference information

40. Mutation Databases: Other examples Atlas of Genetics and Cytogenetics in Oncology and Haematology Database of Germline p53 Mutations SV40 Large T-Antigen Mutant Database KinMutBase � Disease causing kinase mutations

41. Protein Databases Protein sequences collection Clustering of protein data into families Specialized protein sites Organism Function Large variety of enzymes

42. Protein Databases: InterPro a database of protein families, domains and functional sites in which identifiable features found in known proteins can be applied to unknown protein sequences amalgamating the major protein signature databases, data have been manually integrated and curated and are available in InterPro PROSITE Pfam PRINTS ProDom SMART TIGRFAMs Home Home

43. Protein Databases:ProtoNet provides global classification of the proteins, from the SWISS-PROT database into hierarchical clusters clustering is based on an all-against-all BLAST similarity search

44. Protein Databases:iProClass an integrated resource that provides comprehensive family relationships and structural/functional features of proteins currently consists of non-redundant PIR and SwissProt/TrEMBL proteins 36,200 PIR superfamilies 145,300 families 5720 domains 1300 motifs 280 post-translational modification sites links to over 50 biological databases.

45. Protein Databases: Other Examples Nuclear Protein Database � Proteins localized in the nucleus PLANT-Pls � Plant protease inhibitors SWISS-PROT/TrEMBL � Curated protein sequences SENTRA � Sensory signal transduction proteins Ribonuclease P Database

46. Protein Sequence Motifs Alignment of protein sequences Organization of proteins into families

47. Protein Sequence Motifs:BLOCKS multiply aligned ungapped segments corresponding to the most highly conserved regions of proteins Tools: Block Searcher -- compare a protein or DNA sequence to a database of protein blocks Get Blocks -- retrieve blocks Block Maker -- create new blocks

48. Protein Sequence Motifs:Pfam a large collection of multiple sequence alignments and hidden Markov models covering many common protein domains and families. For each family in Pfam you can: Look at multiple alignments View protein domain architectures Examine species distribution Follow links to other databases View known protein structures

49. Protein Sequence Motifs:PROSITE database of protein families and domains. It consists of biologically characterized sites, patterns and profiles that help to reliably identify to which known protein family (if any) a new sequence belongs currently contains patterns and profiles specific for more than a thousand protein families or domains. each of these signatures comes with documentation providing background information on the structure and function of these proteins

50. Protein Sequence Motifs: Other Examples ASC � Active Sequence Collection � Biologically active oligopeptides ClusTr � Automatic classification of SWISS-PROT and TrEMBL proteins TMPDB � Experimentally-characterized transmembrane topology O-GLYCBASE � O- and C- linked glycosylation sites in proteins

51. RNA Sequences Repository of RNA sequences RNA structure data RNA metabolism information Specialized site by organism, function, etc

52. RNA Sequences:HyPaLib contains annotated structural elements characteristic for certain classes of structural and/or functional RNAs developing software tools that allow a user to search sequence databases for any pattern in HyPaLib

53. RNA Sequences:Rfam a collection of multiple sequence alignments and covariance models representing non-coding RNA families allow the user to search a query sequence against a library of covariance models, and view multiple sequence alignments and family annotation

54. RNA Sequences:tRNA sequences compilation of tRNA Sequences and Sequences of tRNA genes

55. RNA Sequences:Other Examples 16S and 23S Ribosomal RNA Mutation Database ACTIVITY � functional DNA/RNA site activity PLANTncRNAs � Plant non-coding RNAs RNA Modification Database � Naturally modified nucleosides in RNA

56. Structure Information on protein structure derived from physical data � crystallography, NMR Classification of proteins according to tertiary structures Specialized site for specific proteins

57. Structure:ASTRAL provides databases and tools useful for analyzing protein structures and their sequences Partially derived from the SCOP database (Structural Classification of Proteins)

58. Structure:SCOP Comprehensive ordering of proteins to know structures based on their evolutionary and structural relationships Protein domains are grouped into species and hierarchically classified in families superfamilies, folds, and classes

59. Structure:PDB Structure data determined by X-ray crystallography and NMR

60. Structure: Other Examples CADB � conformation angles of protein structures, with associated crystallographic data Database of Macromolecular Movements DSDBase � Disulfide Bonds in proteins PSSH � alignment between sequences and tertiary structures SUPERFAMILY � Assignments of proteins to structural superfamilies

61. Other Databases Intermolecular Interactions Metabolic Pathways and Cellular Regulation Pathology Proteome Resources Retrieval Systems and Database Structure Transgenics Varied Medical Content

62. Other Databases:  Intermolecular Interactions BIND � Molecular interactions, complexes and pathways DIP (Database of Interacting Proteins) � Experimentally determined protein-protein interactions KDBI � Kinetic data on biomolecular interactions

63. Other Databases: Metabolic Pathways and Cellular Regulation KEGG � Kyoto Encyclopedia of Genes and Genomes MetaCyc � Metabolic Pathways and Enzymes from Various organisms PathDB EcoCyc � E. coli K-12 genome and pathway data PRODORIC � gene regulation and regulatory networks in prokaryotes

64. Other Databases:Pathology BayGenomics � cardiovascular and pulmonary disease INFEVERS � hereditary inflammatory disorder GOLD.db � lipid-associated disorders Mouse Tumor Biology Database

65. Other Databases: Proteome Resources GELBANK � 2D gel data repository REBASE � Restriction enzymes and associated methylases SWISS-2DPAGE � Annotated two-dimensional gel electrophoresis database

66. Other Databases: Retrieval Systems and Database Structure TESS � Transcription Element search system Virgil � Database interconnectivity

67. Other Databases:Transgenics Cre Transgenic database � Cre transgenic mouslines Transgenic/targeted mutation database � information on transgenic animals and targeted mutations

68. Other Databases: Varied Medical Content Tree of Life � phylogeny and biodiversity PubMed � biomedical literature NCBI Taxonomy Browser � organisms with at least one sequence deposited in the database Pharmgkb � Pharmacogenomics and variations in drug response based on human variation

69. The Rat Genome Database Data Tools Operations

70. The Rat Genome Database: data Genes Maps and Markers QTLs Strains Homologs

71. The Rat Genome Database: tools VCMap Mapserver Meta Gene Genome Scanner Ontology Browser

72. The Rat Genome Database: operations Curation Data QC and Loading Data development Tool development

73. The Rat Genome Database Operations: Curation Information gathering from peer-reviewed work Coordination with other model organism data bases Data quality policy development and assessment

74. The Rat Genome Database Operations: data development Development of data integration strategies Development of ontology annotation protocols Some development of curation policies Outreach Ontology development

75. The Rat Genome Database Operations: tool development Ontology system development Systems analysis Tool integration Tool building Software system migration