Essential Bioinformatics and Biocomputing (LSM2104: Section I) Biological Databases and Bioinformatics Software Prof. Chen Yu Zong Tel: [phone] Email: [e-mail] http://xin.cz3.nus.edu.sg Room 07-24, level 7, SOC1, NUS January 2003

1
Essential Bioinformatics and Biocomputing
(LSM2104 Section I) Biological Databases
andBioinformatics SoftwareProf. Chen Yu
ZongTel 6874-6877Email csccyz_at_nus.edu.sghttp
//xin.cz3.nus.edu.sgRoom 07-24, level 7, SOC1,
NUSJanuary 2003
2
Essential Bioinformatics and Biocomputing
(LSM2104 Section I) Four lecturesPart 1
Biological databasesLecture 2. Biological
information and databasesLecture 3. More
databases, retrieval systems, and database
searching Part 2 SoftwareLecture 4.
Examples of the applications of bioinformatics
software and basic
principlesLecture 5. Overview of bioinformatics
software
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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

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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

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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)

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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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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. 2002
  Jan 130(1)1-12.

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Biological databases

• Lists of biological databases
• INFOBIOGEN Catalog of Databases
  http//www.infobiogen.fr/services/dbcat/
• Nucleic Acids Research Database Listing
• http//nar.oupjournals.org/cgi/content/fu
  ll/30/1/1/DC1
• 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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Biological databases

• INFOBIOGEN Catalog of Databases
• Type of database
  No of records
• DNA
  87
• RNA
  29
• Protein
  94
• Genomic
  58
• Mapping
  29
• Protein
  structure 18
• Literature
  43
• Miscellaneous
  153
• Total
  511

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Biological databases- in Nucleic Acids Research
Type of database
No of records Major Sequence Repositories
7 Comparative Genomics
7 Gene Expression
20 Gene Identification and Structure
30 Genetic and Physical Maps
10 Genomic Databases
48 Intermolecular Interactions
5 Metabolic Pathways and Cellular Regulation
12 Mutation Databases 33 Pathology
8 Protein Databases 50 Protein Sequence
Motifs 18 Proteome Resources 7 RNA
Sequences 26 Retrieval Systems and Database
Structure 3 Structure 32 Transgenics
2 Varied Biomedical Content 18 TOTAL
336
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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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PubMed web-site (http//www3.ncbi.nlm.nih.gov/entr
ez/query.fcgi?dbPubMed )
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PubMed Search (http//www3.ncbi.nlm.nih.gov/entrez
/query.fcgi?dbPubMed )
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
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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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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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DNA databases

• GenBank database (http//www.ncbi.nih.gov/Genbank/
  )
• 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, NCBIs integrated
  retrieval system (studied later)
• Sequence similarity search tools BLAST (studied
  later)
• EMBL nucleotide sequence database
  (http//www.ebi.ac.uk/embl/)
• 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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DNA databases GenBank Web page
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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 2.4.1.90).

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A GenBank entry HEADER
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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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GenBank entry - FEATURES
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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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Biological databases GenBank - SEQUENCE
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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_021877 Homo sapiens chromosome
  1 working draft sequence segment)
• Some entries have contig information instead of
  sequence information. (NT_021877 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. (AK007430. Mus
  musculus 10 d...gi12840976).
• Some annotations are predicted using automated
  analysis. These should also be used with caution.
  (XM_131483 Mus musculus simi...gi20832685).

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GenBank - Statistics

• Year Base Pairs Sequences
• 680338
  606
• 101008486 78608
• 11101066288 10106023
• 15849921438 14976310
• Data size is large and increases fast

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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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Biological databases OMIM Online Mendelian
Inheritance in Man (http//www.ncbi.nlm.nih.gov/Om
im/)

• 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. 2002 30 52-55.

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Biological databases OMIM web-page
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Biological databases OMIM search engine
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Biological databases OMIM statistics

• All Entries 14088
• Established Gene Locus 10476
• Phenotype Descriptions 1194
• Other Entries 2418

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Biological databases

• Protein databases
• SWISS-PROT (http//us.expasy.org/sprot/sprot-top.h
  tml) 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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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)

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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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SWISS-PROT web-page
35
SWISS-PROT entry P00709
36
(No Transcript)
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SWISS-PROT entry P00709
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SWISS-PROT entry P00709
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Biological databases Protein structure
database PDB (http//www.pdb.org)

• 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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Biological databases PDB web-pagehttp//www.rcsb
.org/pdb/
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Biological databases A PDB entryhttp//www.rcsb.
org/pdb/
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Biological databases PDB statistics
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Biological databases Summary of Todays 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 gt12M since
  1960)
• Large amount of data for sequence (DNA gt14M,
  Protein gt 120K)
• Fair amount of data for 3D structure (Protein
  gt14K, Nucleic acid gt1K)