1. Essential Bioinformatics and Biocomputing (LSM2104: Section I) Biological Databases and Bioinformatics Software Prof. Chen Yu Zong Tel: Room 07-24, level 7, SOC1, NUS January 2003

2. Essential Bioinformatics and Biocomputing (LSM2104: Section I) Four lectures Part 1: Biological databases: Lecture 2. Biological information and databases Lecture 3. More databases, retrieval systems, and database searching Part 2: Software: Lecture 4. Examples of the applications of bioinformatics software and basic principles Lecture 5. Overview of bioinformatics software

3. Part 1: Biological databases
Part 1 outline:
Biological information and databases
Overview and definition, types of biological databases
2. Popular databases, records, data format
Genbank, SwissProt, OMIM, PDB, KEGG, BIND, Pfam, PROSITE, PubMed
3. Accessing biological databases, retrieval systems
Entrez, SRS
4. Searching biological databases
Data quality, coverage, redundancy, errors
Textbook:
--T.K.Atwood and D.J. Parry Smith, Introduction to Bioinformatics.
Biological databases: chapters 3 and 4
Essential Bioinformatics and Biocomputing (LSM2104), NUS

4. Biological Information
Cancer as an
example:
Genes:
Growth Genes
Tumor
suppressor genes
Proteins:
Growth Factors
Enzymes
Receptors
Pathways:
Cell death
Systems:
Immune system
Blood supply
Function:
Role of proteins
Molecular
interactions
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5. Biological Information
Nucleic acids:
DNA sequence, genes, gene products (proteins), mutation, gene coding, distribution patterns, motifs
Genomics: genome, gene structure and expression, genetic map, genetic disorder
RNA sequence, secondary structure, 3D structure, interactions
Proteins:
Protein sequence, corresponding gene, secondary structure, 3D structure, function, motifs, homology, interactions
Proteomics: expression profile, proteins in disease processes etc.
Ligands and drugs (inhibitors, activators, substrates, metabolites)
Essential Bioinformatics and Biocomputing (LSM2104), NUS

6. Biological Information
Pathways:
Molecular networks, biological chain events, regulation, feedback, kinetic data
Function:
Binding sites, interactions, molecular action (binding, chemical reaction, etc.)
Biological effect (signaling, transport, feedback, regulation, modification, etc.)
Functional relationship, protein families, motifs, and homologs
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7. Essential Bioinformatics and Biocomputing (LSM2104), NUS
Biological databases
Purpose
To disseminate biological data and information
To provide biological data in computer-readable form
To allow analysis of biological data
A database needs to have at minimum a specific tool for searching and data extraction.
Web pages, books, journal articles, tables, text files, and spreadsheet files cannot be considered as databases
Reading materials:
Baxevanis AD.The Molecular Biology Database Collection: 2002 update. Nucleic Acids Res Jan 1;30(1):1-12.
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8. Essential Bioinformatics and Biocomputing (LSM2104), NUS
Biological databases
Lists of biological databases
INFOBIOGEN Catalog of Databases
Nucleic Acids Research Database Listing
These serve as starting point of biological databases.
More than 500 databases have been catalogued to date and those from the two listings satisfy minimal criteria for the content, access, and quality.
Other sites as a starting point.
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9. Essential Bioinformatics and Biocomputing (LSM2104), NUS
Biological databases
INFOBIOGEN Catalog of Databases
Type of database No of records
DNA
RNA
Protein
Genomic
Mapping
Protein structure
Literature
Miscellaneous
Total
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10. Biological databases- in Nucleic Acids Research
Type of database No of records
Major Sequence Repositories
Comparative Genomics
Gene Expression
Gene Identification and Structure
Genetic and Physical Maps
Genomic Databases
Intermolecular Interactions
Metabolic Pathways and Cellular Regulation 12
Mutation Databases 33
Pathology 8
Protein Databases 50
Protein Sequence Motifs 18
Proteome Resources 7
RNA Sequences
Retrieval Systems and Database Structure 3
Structure
Transgenics 2
Varied Biomedical Content 18
TOTAL
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11. Literature databases – PubMed (MedLine)
1. It contains entries for more than 11 million abstracts of scientific publications.
2. It enables user to do keyword searches, provides links to a selection of full articles, and has text mining capabilities, e.g. provides links to related articles, and GenBank entries, among others.
3. Efficient searching PubMed requires some skill. For example, searching with a keyword “interleukin” returns 108,366 matches.
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12. Essential Bioinformatics and Biocomputing (LSM2104), NUS
PubMed web-site ( )
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13. Essential Bioinformatics and Biocomputing (LSM2104), NUS
PubMed Search ( )
Key Word
No. of Entries
Cancer
1.45M
Blood supply
22K
Protein
3.9K
Enzyme
1.5K
Cancer treatment by targeting blood supply:
Cancer growth depends on blood supply (why?) and thus requires the growth of new blood vessels – angiogenesis
Proteins involved in angiogenesis may be potential anticancer targets
You can find some of these targets
by searching Pubmed
Key word “cancer angiogenesis enzyme drug” produces 856 entries
Cancer
Blood supply
Enzyme
Drug
500
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14. Nucleic Acids databases
What info are in these databases:
DNA sequence, genes, gene products (proteins), mutation, gene coding, distribution patterns, motifs
Genomics: genome, gene structure and expression, genetic map, genetic disorder
RNA sequence, secondary structure, 3D structure, interactions
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15. Nucleic Acids databases
DNA databases – GenBank, EMBL, DDBJ
1. General purpose databases focusing on DNA sequences and their properties
2. GenBank, EMBL-bank and DDBJ exchange data to ensure comprehensive worldwide coverage and accession numbers are managed consistently between the three centers.
Reading materials:
Textbook, chapter 4
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16. Essential Bioinformatics and Biocomputing (LSM2104), NUS
DNA databases
GenBank database (
Contains publicly available DNA sequences from more than 100,000 organisms.
Also contains derived protein sequences, and annotations describing biological, structural, and other relevant features.
Accessible through Entrez, NCBI’s integrated retrieval system (studied later)
Sequence similarity search tools: BLAST (studied later)
EMBL nucleotide sequence database (
Contains nucleotide sequences collected from all public sources.
Accessible through Sequence Retrieval System (SRS) which allows keyword searching (studied later)
Sequence similarity search tools: Blitz, Fasta, and BLAST (studied later)
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17. DNA databases: GenBank Web page
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18. Essential Bioinformatics and Biocomputing (LSM2104), NUS
DNA databases
An Example from GenBank– flat file
Human Alpha-Lactalbumin gene
This protein is a complex of 2 proteins A and B. In the absence of the
B protein, the enzyme catalyzes the transfer of
galactose from UDP-galactose to Nacetylglucosamine (cf. EC ).
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19. A GenBank entry – HEADER
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20. GenBank Entry – Links provided in the Header
MapViewer – find the gene position in chromosome
Related Sequences – other entries related to this gene (or sequence)
OMIM– link to catalog of human genes and genetic disorders
Protein – retrieve protein record from GenPept
Medline and PubMed –literature abstracts related to this gene
Taxonomy – Classification of organisms
UniGene – Unified gene data
UniSTS – Unified sequence tagged sites, marker and mapping data
LinkOut – links to publishers, aggregators libraries, biological databases, sequence centers, and other Web resources
REFSEQ – reference sequence standards
Note: These links are representative. Other links may also be found in GenBank entries.
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21. GenBank entry - FEATURES
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22. GenBank Entry– Links provided in the Feature section
LocusID – locus and display of genomic and mRNA sequences MIM – Link to OMIM description, other entries for this sequence EC_number – link to the corresponding cataloged enzymes Protein_id – retrieve protein record from GenPept CD– conserved protein domain (SMART), CDD – conserved protein domain (Pfam).
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23. Biological databases: GenBank - SEQUENCE
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24. Essential Bioinformatics and Biocomputing (LSM2104), NUS
GenBank - NOTES
Majority of GenBank entries have similar form to our example.
When accessing the database, the following needs to be noticed:
Some entries are huge, containing as much as 30,000 lines. (NT_ Homo sapiens chromosome 1 working draft sequence segment)
Some entries have contig information instead of sequence information. (NT_ Homo sapiens chromosome 1 working draft sequence segment)
Some entries are derived from cDNA sequences and thus represent putative genes/proteins. These should be used with caution. (AK Mus musculus 10 d...[gi: ]).
Some annotations are predicted using automated analysis. These should also be used with caution. (XM_ Mus musculus simi...[gi: ]).
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25. Essential Bioinformatics and Biocomputing (LSM2104), NUS
GenBank - Statistics
Year Base Pairs Sequences
Data size is large and increases fast
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26. Essential Bioinformatics and Biocomputing (LSM2104), NUS
Biological Databases
Database Searching
Databases must have methods for accessing and extracting data stored.
The most basic search is keyword searching
Keywords can be any word that occurs somewhere in the database
records. It can be the name of the gene or protein (e.g. lactalbumin),
species (e.g.homo sapiens, human), a taxonomy term
(e.g.primates), or a word from the reference title (e.g. cancer)
Others include: Entry Id number, sequence
Databases typically have hyperlinks that provide access to additional information related to the entry from other sources.
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27. Essential Bioinformatics and Biocomputing (LSM2104), NUS
Biological databases: OMIM Online Mendelian Inheritance in Man (
The OMIM database contains abstracts and texts describing genetic disorders to support genomics efforts and clinical genetics. It provides gene maps, and known disorder maps in tabular listing formats. Contains keyword search.
Hamosh A. et al. Online Mendelian Inheritance in Man (OMIM), a knowledge base
of human genes and genetic disorders Nucleic Acids Res :
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28. Biological databases: OMIM web-page
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29. Biological databases: OMIM search engine
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30. Biological databases: OMIM statistics
All Entries : Established Gene Locus : Phenotype Descriptions : 1194 Other Entries : 2418
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31. Essential Bioinformatics and Biocomputing (LSM2104), NUS
Biological databases
Protein databases
SWISS-PROT ( is a curated database focusing on high level of annotation (sequence, function, structure, post-translational modifications, variants, etc.) of proteins.
TrEMBL is Computer-annotated supplement to SWISS-PROT
Reading materials: Textbook, chapter 3
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32. Essential Bioinformatics and Biocomputing (LSM2104), NUS
Protein databases
What are in these databases:
Protein sequence, corresponding gene, secondary structure, 3D structure, function, motifs, homology, interactions
Proteomics: expression profile, proteins in disease processes etc.
Ligands and drugs (inhibitors, activators, substrates, metabolites)
Essential Bioinformatics and Biocomputing (LSM2104), NUS

33. Protein databases – SWISS-PROT
Notes:
SWISS-PROT provides high-quality annotations and detailed info about sequence, structural, functional, and other properties of proteins.
It provides a rich set of links to other sources of information on SWISS-PROT entries. Unfortunately, some of the links will not work at all times, because of the dynamical change of the Web.
It also provides a rich set of protein analysis tools.
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34. Essential Bioinformatics and Biocomputing (LSM2104), NUS
SWISS-PROT web-page
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35. Essential Bioinformatics and Biocomputing (LSM2104), NUS
SWISS-PROT entry P00709
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36. Essential Bioinformatics and Biocomputing (LSM2104), NUS

37. Essential Bioinformatics and Biocomputing (LSM2104), NUS
SWISS-PROT entry P00709
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38. Essential Bioinformatics and Biocomputing (LSM2104), NUS
SWISS-PROT entry P00709
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39. Essential Bioinformatics and Biocomputing (LSM2104), NUS
Biological databases: Protein structure database: PDB (
More than 18,000 macromolecular structures on proteins, peptides, viruses, protein/nucleic acids complexes, nucleic acids, and carbohydrates.
Among the oldest databases – the first structure was deposited in 1972.
New deposited structures has been steadily growing (3298 in 2001, and 1486 Jan 1-June 5, 2002).
Determined mainly by the X-ray diffraction and NMR.
It Contains tools for keyword search, comprehensive visualization, and information extraction – such as sequence, geometry, and structural neighbors details.
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40. Biological databases: PDB web-page http://www.rcsb.org/pdb/
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41. Biological databases: A PDB entry http://www.rcsb.org/pdb/
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42. Biological databases PDB statistics
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43. Biological databases Summary of Today’s lecture
Types of Biological information, data and databases
Simple data retrieval method.
Popular databases: Pubmed, Genbank, SwissProt, OMIM, PDB
Statistics:
Large number of publications (MEDLINE: >12M since 1960)
Large amount of data for sequence (DNA: >14M, Protein: > 120K)
Fair amount of data for 3D structure (Protein >14K, Nucleic acid >1K)
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