1. Databases (“knowledge bases”) used in genome analysis
Michael Y. Galperin
National Center for Biotechnology Information
National Library of Medicine
National Institutes of Health
Bethesda, Maryland, USA

2. Growth in genome sequencing

3. Working Draft Sequence
gaps

4. J. Smith - a very common name
Structure - a very common term
Glutamine amidotransferase - less common term but not
a very good descriptor

5. A different professor Janet Smith
Another Janet Smith in the news

6. Glutamine for sale

7. Tools of trade for the “armchair scientist”
Databases
PubMed and other NCBI databases
Biochemical databases
Protein domain databases
Structural databases
Genome comparison databases
Tools
CDD / COGs
VAST / FSSP

8. Types of databases Archival or Primary Data Curated or Processed Data
Text: PubMed
DNA Sequence: GenBank
Protein Sequence: Entrez Proteins, TREMBL
Protein Structures: PDB
Curated or Processed Data
DNA sequences : RefSeq, LocusLink, OMIM
Protein Sequences: SWISS-PROT, PIR
Protein Structures : SCOP, CATH, MMDB
Genomes: Entrez Genomes, COGs
Nucleic Acids Research: Database Issue each January 1 Articles on ~100 different databases

10. The National Center for Biotechnology Information (NCBI)
Created as a part of the National Library of Medicine, National Institutes of Health in 1988
Establish public databases
Research in computational biology
Develop software tools for sequence analysis
Disseminate biomedical information
Tools: BLAST(1990), Entrez (1992)
GenBank (1992)
Free MEDLINE (PubMed, 1997)
Other databases: dbEST, dbGSS, dbSTS, MMDB, OMIM, UniGene, Taxonomy, GeneMap, SAGE, LocusLink, RefSeq

11. What is GenBank?
Archival nucleotide sequence database
Sample slogans: “Easy deposits, unlimited withdrawals, high interest”, “All bases covered”, “Billions and billions served”
Data are shared nightly among three collaborating databases:
GenBank at NCBI - Bethesda, Maryland, USA
DNA Database of Japan (DDBJ) at NIG - Mishima, Japan
European Molecular Biology Laboratory Database (EMBL) at EBI - Hinxton, UK

12. Some guiding principles of working with GenBank
GenBank is a nucleotide-centric view of the information space
GenBank is a repository of all publically available sequences
In GenBank, records are grouped for various reasons
Data in GenBank is only as good as what you put in

13. NCBI databases and their links
Word Weight
VAST
BLAST
Phylogeny
Article Abstracts
Medline
3-D Structure
3 D Structure
Taxonomy
MMDB
Genomes
Nucleotide Sequences
Protein Sequences

14. Entrez: An integrated search and retrieval system

20. PubMed book links

21. GenBank Record Locus Name Accession Number gi Number Medline ID
[rest of protein sequence deleted for brevity]
[rest of nucleotide sequence deleted for brevity]
gi Number
Medline ID
Protein Sequence
GenPept ID
Nucleotide Sequence

24. Archival databases are unreliable
Misinterpreted experimental results
Annotations base on low similarity gi| cDNA 5' end similar to similar to arrest- defective protein isolog (H. sapiens)
gi| very hypothetical protein (S. pombe)
Biologically senseless annotations Deinococcus: head morphogenesis protein
Arabidopsis: separation anxiety protein-like
Yersinia: automembrane protein H
H. pylori - brute force protein
S. cerevisiae - inside intron 7
Propagated mistakes of sequence comparison (e.g. ABC1/ABC)

25. Advanced Neighbors: BLink

26. BLink

38. Protein sequence motif is a descriptor of a protein family
Glutamine amidotransferase class I
[PAS]-[LIVMFYT]-[LIVMFY]-G-[LIVMFY]-C- [LIVMFYN]-G-x-[QEH]- x-[LIVMFA]
[C is the active site residue]
Glutamine amidotransferase class II <x(0,11)-C-[GS]-[IV]-[LIVMFYW]-[AG]

47. purF gene neighbors

48. Searching MMDB

49. Principles of structural alignment
Dali: Looks for minimal RMSD between Ca atoms. Calculate Ca - Ca distance matrices, then identifies the longest alignable segments
VAST (Vector Alignment Search Tool) looks for pairs of secondary structure elements (a-helices, b-strands) that have similar orientation and connectivity

50. Dali alignment of Tyr phosphatase

51. VAST Structure Neighbors

52. Structure Summary
BLAST neighbors
VAST neighbors
Cn3D viewer

53. Cn3D : Displaying Structures
Chloroquine

54. Structure Neighbors

55. Use of structural alignments
Chloroquine
NADH

56. Online Mendelian Inheritance in Man
A catalog of human genes and genetic disorders

57. OMIM record for Presenilin 1 (PSEN1)
Contents
Additional info in OMIM
Each record provides a state of the art summary of current knowledge
Associated LocusLink record
External resources
Extensive references to literature

58. OMIM Search Results by Titles
alzheimer AND presenilin 1

59. Entrez Genome: Gene Location
View of chromosome 14
Multiple Maps
STSs, ESTs, etc.
Gene Name

60. Integrated View of Chromosome 7
Entrez Genomes Map Viewer
Chromosome 7
GenBank Map Contig Map STS Map
Multiple Maps
STSs, ESTs, etc.

61. Entrez Genome: Gene Location
View of chromosome 14
Gene Name

62. Entrez Genome: Gene Location
Entrez Genomes Map Viewer
Chromosome 14 Cytogenetic map
Location of PSEN1 and surrounding genes

63. LocusLink

64. LocusLink Multiple Organisms Text querying Alphabetical listings
alzheimer
Curated Resource
Central hub of information for human, mouse, rat, zebrafish, and fruit fly loci
Text querying
Alphabetical listings
Approved symbol
Stable Locus ID
Description
Genome Position
External Links

65. LocusLink
RefSeq
GenBank
OMIM
UniGene
dbSNP

66. LocusLink: LocusID 5663 PSEN1

67. National Center for Biotechnology Information
Directed by Dr. David J. Lipman