Download Databases in Bioinformatics

Archives and Information
Retrieval
Lecture by; Ms. AQSAD
RASHDA
BIOINFORMATICS
Database indexing and specification of search terms
• An index is a set of pointers to information
in a database
• Search terms
• Entries: discrete coherent parcels of
information.
• The information retrieval software
• Keywords
• AND’ NOT
• Follow-up questions
The archives
Primary data collections related to biological
macromolecules include:
􀂃 Nucleic acid sequences, including whole-genome
projects
􀂃 Amino acid sequences of proteins
􀂃 Protein and nucleic acid structures
􀂃 Small-molecule crystal structures
􀂃 Protein functions
􀂃 Expression patterns of genes
􀂃 Publications
UK MRC Human Genome Mapping Project Resource Centre
http://www.hgmp.mrc.ac.uk
Nucleic acid sequence databases
• Triple partnership of:
• National Center for Biotechnology
Information (USA)
• EMBL Data Library (European
Bioinformatics Institute, UK)
• DNA Data Bank of Japan (National
Institute of Genetics, Japan).
Entries have a life cycle
Nucleotide sequence databases
• EMBL, GenBank, and DDBJ are the three
primary nucleotide sequence
databases
• EMBL www.ebi.ac.uk/embl/
• GenBank
www.ncbi.nlm.nih.gov/Genbank/
• DDBJ www.ddbj.nig.ac.jp
The EMBL data library entry for the bovine pancreatic trypsin inhibitor gene
Identification
Accession
Date
Description
Keyword
Organism Source
Organism
Classification
Reference Number
Reference Position
Reference Author
Reference Title
Reference Location
Feature Table
Header
FT: The feature table
may indicate regions
that
1. perform or affect
function
2. interact with other
molecules
3. affect replication
4. are involved in
recombination
5. are a repeated unit
6. have secondary or
tertiary structure
7. are revised or
corrected
Sequence Header
Protein sequence databases
• SWISS-PROT: The Swiss Institute of
Bioinformatics collaborates with the EMBL
Data Library to provide an annotated
database of amino acid sequences called
SWISS-PROT.
• PIR: Another protein sequence database
is produced by The PIR International
http://pir.georgetown.edu/
PIR entry for the amino acid sequence of Bovine pancreatic trypsin inhibitor
Databases associated with SWISS-PROT
• ENZYME DB, and PROSITE
• The ENZYME DB stores the following information about enzymes:
• EC Number: a numerical identifier assigned by the Enzyme
Commission (authorized by the International Union of Biochemistry
and Molecular Biology; see
• http://www.chem.qmw.ac.uk/iubmb/enzyme/)
• Recommended name
• Alternative names, if any
• Catalytic activity
• Cofactors, if any
• Pointers to SWISS-PROT and other data banks
• Pointers to disease associated with enzyme deficiency if any known
A Sample Entry in ENZYME DB
The PIR and associated databases
• The PIR maintains several databases about proteins:
1. PIR-PSD: the main protein sequence database
2. iProClass: classification of proteins according to structure and
function
3. ASDB: annotation and similarity database; each entry is linked to a
list of similar sequences
4. P/R-NREF: a comprehensive non-redundant collection of over 800
000 protein sequences merged from all available sources
5. NRL3D: a database of sequences and annotations of proteins of
known structure deposited in the Protein Data Bank
6. ALN: a database of protein sequence alignments, and
7.RESID: a database of covalent protein structure modifications (recall
that important structural features of proteins such as disulphide
bridges are not inferrable from gene sequences, and will not appear
in protein sequence databases derived solely by translation of
genomic data)
Databases of structures
•
Structure databases archive, annotate and distribute sets of atomic
coordinates
• Protein Data Bank (PDB).
• The information contained includes:
1. What protein is the subject of the entry, and what species it came
from
2. Who solved the structure, and references to publications describing
the structure determination
3. Experimental details about the structure determination, including
information related to the general quality of the result such as
resolution of an X-ray structure determination and stereochemical
statistics
4. The amino acid sequence
5. What additional molecules appear in the structure, including
cofactors, inhibitors, and water molecules
6. Assignments of secondary structure: helix, sheet
7. Disulphide bridges
8. The atomic coordinates
Protein data bank entry 2TRX, E. coli thioredoxin
Indicators of structure quality
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X-ray crystal structure analysis
Nuclear Magnetic Resonance
Web Resource; Protein and Nucleic Acid Structures
Home page of protein data bank:
http://www.rcsb.org
Home page of EBI macromolecular structure database:
http://msd.ebi.ac.uk/
Home page of BioMagResBank:
http://www.bmrb.wisc.edu/
Searching the protein data bank:
Home page of SCOP (Structural classification of proteins):
http://scop.mrc-lmb.cam.ac.uk/scop/
List of browsers:
http://pdb-browsers.ebi.ac.uk/browse_it.shtml
OCA:
http://oca.ebi.ac.uk/oca-bin/ocamain
Crystallisation
Hanging drop method / vapour diffusion method
Microscope
1-Dilute protein solution
Microscope slide
many different
conditions of 1&2
must be tried
2-Concentrated salt solution
Crystal
Slide courtesy from Shoshana Wodak
Determination of protein
structure
Diffraction pattern
Atomic model
Slide courtesy from Shoshana Wodak
The resolution problem
q
q
q
A high resolution protein structure : 1.5 - 2.0 Å resolution
Slide courtesy from Shoshana Wodak
Nuclear Magnetic Resonance
(NMR)
Source: Branden & Tooze (1991)
Classifications of protein structures
• SCOP: Structural Classification of Proteins
• CATH:
Class/Architecture/Topology/Homology
• DALI:Classification of protein domains
Based on extraction of similar structures
from distance matrices.
[http://www.ebi.ac.uk/dali/domain/]
• CE: A database of structural alignments
CATH - A protein domain
classification
• In CATH, protein
domains are
classified
according to a tree
with 4 levels of
hierarchically
– Class
– Architecture
– Topology
– Homology
Class
Architecture
Topology
Figure from Shoshana Wodak
Specialized, or 'boutique' databases
• VIPER (Virus Particle ExploreR) treats crystal structures of
icosahedral viruses.
• In the field of immunology:
• IMGT, the international ImMunoGeneTics database, is a
high-quality integrated database specializing in
Immunoglobulins (Ig), T-cell receptors (TcR) and Major
Histocompatibility Complex (MHC) molecules of all
vertebrate species.
• The IMGT server provides a common access to all
Immunogenetics data.
• At present, it includes two databases: IMGT/LIGM-DB, a
comprehensive database of immunoglobulin and T-cell
receptor gene sequences from human and other
vertebrates, with translation for fully annotated sequences,
and IMGT/HLA-DB, a database of the human MHC referred
to as HLA (Human Leucocyte Antigens)
Web Resource: Databases for Specific
Protein Families
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Protein kinases
http://www.sdsc.edu/kinases/
HIV proteases
http://www-fbsc.ncifcrf.gov/HIVdb/
Icosahedral viruses
http://mmtsb.scripps.edu/viper/main.html
Immunology
IGMT: http://imgt.cines.fr
KABAT: http://immuno.bme.nwu.edu/
MHCPEP: http://wehih.wehi.edu.au/mhcpep/
Collections of links to databases on specific protein families
http://www2.ebi.ac.uk/msd/Links/family.shtml
KABAT - Database of Sequences of Proteins of Immunological Interest North-Western University (USA)
MHCPEP - Major Histocompatibility Complex Binding Peptides Database Walter and Eliza Hall Institute (Melbourne, Australia)
Expression and proteomics databases
• Expression databases record measurements of mRNA levels,
usually via ESTs (short terminal sequences of cDNA synthesized
from mRNA).
Comparisons of expression patterns give clues to:
(1) the function and mechanism of action of gene products,
(2) how organisms coordinate their control over metabolic processes in
different conditions - for instance yeast under aerobic or anaerobic
conditions,
(3) the variations in mobilization of genes at different stages of the cell
cycle, or of the development of an organism,
(4) mechanisms of antibiotic resistance in bacteria, and consequent
suggestion of targets for drug development
(5) the response to challenge by a parasite
(6) the response to medications of different types and dosages, to
guide effective therapy.