The document provides an overview of biological databases, their structure, and types, including primary and derivative databases. It highlights key features of data organization, the functionality of well-maintained databases, and the role of prominent databases like GenBank and Swiss-Prot. Additionally, it discusses the importance of data integration for revealing inter-related biological information.

1. INTRODUCTION TO
BIOLOGICAL DATABASES

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DATABASES
 Sequence info is stored in databases
 So that they can be manipulated easily
 The db (next slide) are located at diff places
 They exchange info on a daily basis so that
they are up-to-date and are in sync
 Primary db – sequence data

3. WHAT ARE DATABASES?
 Structured collection of information.
 Consists of basic units called records or entries.
 Each record consists of fields, which hold pre-
defined data related to the record.
 For example, a protein database would have
protein entries as records and protein properties as
fields (e.g., name of protein, length, amino-acid
sequence)

4. THE ‘PERFECT’ DATABASE
 Comprehensive, but easy to search.
 Annotated, but not “too annotated”.
 A simple, easy to understand structure.
 Cross-referenced.
 Minimum redundancy.
 Easy retrieval of data.

5. TYPES OF MOLECULAR DATABASES
 Primary Databases
 Original submissions by experimentalists
 Content controlled by the submitter
 Examples: GenBank, Trace, SRA, SNP, GEO
 Derivative Databases
 Derived from primary data
 Content controlled by third party (NCBI)
 Examples: NCBI Protein, Refseq, TPA, RefSNP, GEO datasets, UniGene,
Homologene, Structure, Conserved Domain

6. PRIMARY VS. DERIVATIVE SEQUENCE
DATABASES
GenBank
Sequencing
Centers
TATAGCCG TATAGCCG
TATAGCCG TATAGCCG
Labs
Algorithms
UniGene
Curators
RefSeq
Genome
Assembly
TATAGCCG
AGCTCCGATA
CCGATGACAA
Updated
continually
by NCBI
Updated ONLY
by submitters

7. MAJOR PRIMARY DB
Nucleic Acid Protein
EMBL (Europe) PIR -
Protein Information
Resource
GenBank (USA) MIPS
DDBJ (Japan) SWISS-PROT
University of Geneva,
now with EBI
TrEMBL
A supplement to SWISS-
PROT
NRL-3D

8. IAM: International Advisory
Meeting
ICM: International
Collaborative Meeting
International
Nucleotide Sequence Database
EMBL:
European Molecular Biology
Laboratory
EBI:
European Bioinformatics
Institute
DDBJ: DNA Data Bank of Japan
CIB: Center for Information Biology
and
DNA Data Bank of Japan
NIG: National Institute of Genetics
NCBI:
National Center for Biotechnology
Information
NLM:
National Library of Medicine

9. Protein Databases
In 1988, The Protein Information Resource (PIR), established a
cooperative effort with the Munich Information Center for Protein
Sequences (MIPS) and the Japan International Protein
Information Database (JIPID) , produces the PIR-International .
Protein Sequence Database (PIR-PSD) -- a comprehensive, non-
redundant, expertly annotated, fully classified and extensively
cross-referenced protein sequence database in the public domain.
http://pir.georgetown.edu/
Protein Information Resources (PIR)
SWISSPROT http://www.ebi.ac.uk/swissprot/
The SWISS-PROT Protein Knowledgebase is an annotated
protein sequence database established in 1986. It is
maintained collaboratively by the Swiss Institute for
Bioinformatics (SIB) and the European Bioinformatics
Institute (EBI).

10. NCBI DATABASES

11. THE NATIONAL CENTER FOR
BIOTECHNOLOGY INFORMATION
Created in 1988 as a part of the
National Library of Medicine at NIH
– Establish public databases
– Research in computational biology
– Develop software tools for sequence analysis
– Disseminate biomedical information
Bethesda,MD

12. WEB ACCESS: WWW.NCBI.NLM.NIH.GOV
New Homepage
Common footer
New pages!

13. NCBI DATABASES AND SERVICES
 GenBank primary sequence database
 Free public access to biomedical literature
 PubMed free Medline (3 million searches per day)
 PubMed Central full text online access
 Entrez integrated molecular and literature databases

14. SEQUENCE DATABASES AT NCBI
 Primary
 GenBank: NCBI’s primary sequence database
 Trace Archive: reads from capillary sequencers
 Sequence Read Archive: next generation data
 Derivative
 GenPept (GenBank translations)
 Outside Protein (UniProt—Swiss-Prot, PDB)
 NCBI Reference Sequences (RefSeq)

15. GENBANK - PRIMARY SEQUENCE DB
 Nucleotide only sequence database
 Archival in nature
 Historical
 Reflective of submitter point of view (subjective)
 Redundant
 Data
 Direct submissions (traditional records)
 Batch submissions
 FTP accounts (genome data)

16. GENBANK - PRIMARY SEQUENCE DB (2)
 Three collaborating databases
1. GenBank
2. DNA Database of Japan (DDBJ)
3. European Molecular Biology Laboratory (EMBL) Database

17. The International Nucleotide Sequence
Database Collaboration (INSDC)
EMBL:
European Bioinformatics Institute (EBI)
GenBank:
National Center for Biotechnology Information (NCBI)
http://www.ncbi.nlm.nih.gov/
DDBJ:
National Institute of Genetics (NIG)
http://www.ddbj.nig.ac.jp/
http://www.ebi.ac.uk

18. TRADITIONAL GENBANK RECORD
ACCESSION U07418
VERSION U07418.1 GI:466461
Accession
•Stable
•Reportable
•Universal
Version
Tracks changes in sequence
GI number
NCBI internal use
well annotated
the sequence is the data

19. GENBANK
 First example: prokaryotic gene
 point your browser to:
http://www.ncbi.nlm.nih.gov/entrez
 choose Nucleotide from the Search pull-down menu
 in For box, type X01714 and click Go
 Click the link labeled X01714
 Can “Send To Text” if you want to save the file

23. GENBANK FIELDS
• LOCUS
– size of sequence (in base pairs)
– nature of molecule (e.g. DNA or RNA)
– topology (linear or circular)
• DEFINITION: brief description of gene
• ACCESSION: unique identifier for this (and some
other) databases
• VERSION: lists synonymous or past ID numbers

25. GENBANK FIELDS
 KEYWORDS: list of terms related to entry; can be
used for keyword searching for related data
 SOURCE: common name of relevant organism
 ORGANISM: complete id, with taxonomic
classification
 note that ORGANISM is indented under SOURCE; this
indicates that ORGANISM is a subordinate term, or
subsection, of SOURCE

26. GENBANK FIELDS
• REFERENCE: credits author(s) who initially
determined the sequence; includes subsections:
– AUTHOR
– TITLE
– JOURNAL
– PUBMED
• COMMENT: free-formatted text that doesn’t fit in
another category

27. GENBANK FIELDS: FEATURES: CDS
 gives coordinates from initial nucleotide (ATG) to
last nucleotide of stop codon (TAA)
 several lines follow, listing protein products, reading
frame to use, genetic code to apply and several IDs
for the protein sequence
 /translation section gives computer translation of
sequence into amino acid sequence

30. LAST SECTION: SEQUENCE ITSELF
• This is the most important section in terms of
analysis using other tools
• Can isolate just this section and save the file, as
follows:
– Choose FASTA from the Display pull-down menu (top of
page)
– Choose Text in the Send To pull-down menu
– Use File/Save As to save the file
• use “Text” as file type
• give the file a name that you’ll know to associate with this
particular sequence

32. EXAMPLE 2: EUKARYOTIC MRNA
• Can obtain this example by searching Nucleotide
database for U90223
• Similar to prokaryote example, because we’re
looking at a direct coding sequence for a protein –
not DNA, in other words
• Notes on example:
– KEYWORD field is empty: this is an example of an
incomplete annotation
– remember, you’re looking at a primary database!
– FEATURES field contains some new terms:
• sig_peptide: location of mitochondrial targeting sequence
• mat_peptide: exact boundaries of mature peptide

33. EXAMPLE 3: EUKARYOTIC GENE
• Can obtain this record by searching Nucleotide for
AF018430
• General information:
– LOCUS: same info as previous examples – note the
locus name is different from the accession number this
time
– DEFINITION: specifies exon; remember, protein-coding
regions in eukaryotes are not contiguous as in
prokaryotes
– SEGMENT: indicates this is the second of 4; you’d need
all 4 to reconstruct the mRNA that codes for the protein

34. EUKARYOTIC GENE: FEATURES SECTION
 source subsection includes a /map section:
 indicates chromosome (15)
 arm (q means long arm)
 cytogenic band (q21.1)

35. ‘TAKE HOME MESSAGE’ ADVANTAGES OF
DATA INTEGRATION
 More relevant inter-related information in one place
 Makes it easier to find additional relevant
information related to your initial query
 Potentially find information indirectly linked, but
relevant to your subject of interest
 uncover non-obvious genetic features that explain
phenotype or disease
 Easier to build a ‘story’ based on multiple pieces of
biological evidence