This document provides an introduction to biological databases. It discusses what databases are and features of an ideal database. It describes the relationships between primary sequence databases like GenBank that contain original submissions, and derived databases like RefSeq that are curated by NCBI. Key databases at NCBI are described, including GenBank, RefSeq, and Entrez, which allows integrated searching across multiple databases. The benefits of data integration through linking related information are highlighted.

1. INTRODUCTION TO
BIOLOGICAL DATABASES
SARFARAZ HUSSAIN
Department of Bioinformatics
& Biotechnology GCU-
Faisalabad
NOTE: Most slides derived from NCBI’s field guide
/ sarfraz1412@gmail.com

2. WHAT YOU NEED TO LEARN:
 What is a database and what are the features of
an ideal db?
 What are the relationships/differences between
primary and derived sequence databases?
 What are the benefits of RefSeq?
 Why is data integration useful?

3. 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

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

5. 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)

6. 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.

7. THE CENTRAL DOGMA & BIOLOGICAL
DATA
Protein structures
-Experiments
-Models (homologues)
Literature information
Original DNA Sequences
(Genomes)
Protein Sequences
-Inferred
-Direct sequencing
Expressed DNA sequences
( = mRNA Sequences
= cDNA sequences)
Expressed Sequence Tags
(ESTs)

8. 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

9. 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

10.  PubMed is a free search engine accessing
primarily the MEDLINE database of references
and abstracts on life sciences and biomedical
topics. The United States National Library of
Medicine (NLM) at the
National Institutes of Health maintains the
database as part of the Entrez system of
information retrieval.

11.  Pubmed: click on the drop down menu select the
pubmed option. Type any topic which you want to
find in the search box.

12.  After typing the topic of our interest lots of
research papers will appear on window from
where we select the specific papers for our study.

13. PRIMARY VS. DERIVATIVE SEQUENCE
DATABASES
GenBankGenBank
SequencingSequencing
CentersCenters
GA
GAGA
ATT
ATT
C
CGAGA
ATT
ATT
C
C
AT
GAGA
ATT
C
C GAGA
ATT
C
C
TTGACA
ATTGACTA
ACGTGC
TTGACA
CGTGA
ATTGACTA
TATAGCCG
ACGTGC
ACGTGC
ACGTGC
TTGACA
TTGACA
CGTGA
CGTGA
CGTGA
ATTGACTA
ATTGACTA
ATTGACTA
ATTGACTA
TATAGCCG
TATAGCCGTATAGCCG
TATAGCCGTATAGCCG TATAGCCGTATAGCCG TATAGCCG
CATT
GAGA
ATT
C
C GAGA
ATT
C
C LabsLabs
AlgorithmsAlgorithms
UniGene
CuratorsCurators
RefSeq
Genome
Assembly
TATAGCCG
AGCTCCGATA
CCGATGACAA
Updated
continually
by NCBI
Updated ONLY
by submitters

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

18. DERIVATIVE SEQUENCE
DATABASES

19. FEATURES Location/Qualifiers
source 1..2484
/organism="Homo sapiens"
/mol_type="mRNA"
/db_xref="taxon:9606"
/chromosome="3"
/map="3p22-p23"
gene 1..2484
/gene="MLH1"
CDS 22..2292
/gene="MLH1"
/note="homolog of S. cerevisiae PMS1 (Swiss-Prot Accession
Number P14242), S. cerevisiae MLH1 (GenBank Accession
Number U07187), E. coli MUTL (Swiss-Prot Accession Number
P23367), Salmonella typhimurium MUTL (Swiss-Prot Accession
Number P14161) and Streptococcus pneumoniae (Swiss-Prot
Accession Number P14160)"
/codon_start=1
/product="DNA mismatch repair protein homolog"
/protein_id="AAC50285.1"
/db_xref="GI:463989"
/translation="MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKS
TSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGE
ALASISHVAHVTITTKTADGKCAYRASYSDGKLKAPPKPCAGNQGTQITVEDLFYNIA
TRRKALKNPSEEYGKILEVVGRYSVHNAGISFSVKKQGETVADVRTLPNASTVDNIRS
GENPEPT: GENBANK CDS
TRANSLATIONS
>gi|463989|gb|AAC50285.1| DNA mismatch repair prote...
MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIV...
EDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTAD...
>gi|463989|gb|AAC50285.1| DNA mismatch repair prote...
MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIV...
EDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTAD...

20. REFSEQ: DERIVATIVE SEQUENCE DATABASE
 Curated transcripts and proteins
 Model transcripts and proteins
 Assembled Genomic Regions
 Chromosome records
 Human genome
 microbial
 organelle
ftp://ftp.ncbi.nih.gov/refseq/release/

21. SELECTED REFSEQ ACCESSION
NUMBERS
Curated mRNA
Curated Protein
Curated non-coding RNA
Predicted mRNA
Predicted Protein
Predicted non-coding RNA
Reference Genomic Sequence
Microbial replicons, organelle genomes,
Alternate assemblies
Contig
WGS Supercontig

22. GENBANK TO REFSEQ

23. REFSEQS: ANNOTATION REAGENTS
Genomic DNAGenomic DNA
((NCNC,, NT, NWNT, NW))
Model mRNAModel mRNA (XM)(XM)
(XR)(XR)
Curated mRNACurated mRNA (NM)(NM)
(NR)(NR)
Model proteinModel protein (XP)(XP)
Curated ProteinCurated Protein (NP)(NP)
Scanning....
= ?
GenBank
Sequences
RefSeq

24. REFSEQ BENEFITS
 Non-redundancy
 Updates to reflect current sequence data and biology
 Data validation
 Format consistency
 Distinct accession series
 Stewardship by NCBI staff and collaborators

25. OTHER DERIVATIVE DATABASES
 Expressed Sequences
 dbSNP
 Structure
 Gene
 and more…

26. ENTREZ
FINDING RELEVANT
INFORMATION IN NCBI
DATABASES

27. ENTREZ: A DISCOVERY SYSTEM
Gene
Taxonomy
PubMed
abstracts
Nucleotide
sequences
Protein
sequences
3-D
Structure
3 -D
Structure
Word weight
VAST
BLASTBLAST
Phylogeny
Hard Link
Neighbors
Related Sequences
Neighbors
Related Sequences
BLink
Domains
Neighbors
Related Structures
Pre-computed and pre-compiled data.
•A potential “gold mine” of undiscovered
relationships.
•Used less than expected.
Pre-computed and pre-compiled data.
•A potential “gold mine” of undiscovered
relationships.
•Used less than expected.

28. GLOBAL QUERY: ALL NCBI DATABASES
The Entrez system: 38 (and counting) integrated databasesThe Entrez system: 38 (and counting) integrated databases

29. TRADITIONAL METHOD: THE LINKS MENU
DNA Sequence
Nucleotide – Protein Link
Related Proteins
Protein – Structure Link
3-D Structure

30. THE PROBLEM
 Rapidly growing databases with complex and changing
relationships
 Rapidly changing interfaces to match the above
Result
 Many people don’t know:
 Where to begin
 Where to click on a Web page
 Why it might be useful to click there

31. GLOBAL NCBI (ENTREZ) SEARCH
colon cancercolon cancer

32. GLOBAL ENTREZ SEARCH
RESULTS

33. ENTREZ TIP: START SEARCHES IN
GENE
Other Entrez DBs
HomoloGene
Entrez
Protein
Gene
UniGene
BLink
Homologene:
Gene Neighbors

34. PRECISE RESULTS
MLH1[Gene Name] AND Human[Organism]MLH1[Gene Name] AND Human[Organism]

35. MLH1 GENE RECORD

36. MLH1:LINKS TO SEQUENCE

37. GENEVIEW: HUMAN MLH1 VARIATIONS
ATPase domain

38. ‘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