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Databases in Bioinformatics

(Roald Forsberg)

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Overview

The role of databases in bioinformatics

The structure of databases– Relational databases

– Database Management Systems

– Accessing databases

Types of databases– Data types

– Integrated databases (Entrez)

Nucleotide sequence formats– FASTA format

– GenBank format

– XML formats

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Databases in BioinformaticsBioinformatics – attempted definition:

“The application of computational techniques to understand and organise the information associated with biological macromolecules”

Adapted from Oxford English Dictionary

Biological experiments

Databases

Computational Biology

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Ask your neighbour

• What would you like to do with a database?

• Which types of biological information could be stored in a database?

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Use of databases

• Homology searching:– Use of knowledge from other often more well described organisms such

as the model organisms Mouse, Drosophila, Fugu, C.Elegans etc..– Sequence level – position, annotation– Structural level – proteins, RNA

• Evolutionary analyses:– Phylogenetics– Population genetics– Molecular evolution of genetic elements– Genome evolution

• Primer design• Microarray design• Drug design• Many more……

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General types of databases

• Primary– Raw and non-processed data

• Secondary– Curated – data chosen from criteria– E.g non-redundance, fold

• Tertiary– Data processed– HMM profile

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Structure of relational databases

MEQ147631MEQ147632MEQ147633MEQ147634MEQ147635MEQ147636MEQ147637MEQ147638MEQ147639MEQ147640MEQ147641

EntriesTable 1

Table 2

Table = genetic element

Field = position = chr. 4

Field = size = 3540 bp

Field = coding = true

Field = known EST = true

Field = known structure = false

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Structure of relational databases

File

Database files

Database

Management

system

Interface (WEB)

File File File File File File

Terminal input

scripts DBMS software

SQL language (Structural Query Language)Terminal output

Stored results

Queries

To DMBS

Browser input

scripts

Results from

DMBS

Queries

To data

Structure

of data

Browser output

Result files

Results from

DMBS

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Database management systems

• A software package designed to store and manage databases.

• A computerized record-keeping system• Allows operations such as:

– Adding new files– Inserting data into existing files– Retrieving data from existing files– Changing data– Deleting data– Removing existing files from the database

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Accessing a database

• WEB – graphical user interface (GUI)

• WEB – automated procedures– Batch search with script (Entrez)– Search robots with e-mail updates

• Local– Buy a big computer and a thick cable– Speed improvement

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Protein sequence databasesDatabase URL

Protein sequence(primary)SWISS-PROT www.expasy.ch/sprot/sprot-top.htmlPIR-International www.mips.biochem.mpg.de/proj/protseqdb Protein sequence (composite)OWL www.bioinf.man.ac.uk/dbbrowser/OWL

NRDB www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

Protein sequence (secondary)PROSITE www.expasy.ch/prosite

PRINTS www.bioinf.man.ac.uk/dbbrowser/PRINTS/PRINTS.html

Pfam www.sanger.ac.uk/Pfam/

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Nucleotide sequence databases

• GenBank www.ncbi.nlm.nih.gov/Genbank

• EMBL www.ebi.ac.uk/embl

• DDBJ www.ddbj.nig.ac.jp

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Types of nucleotide data

• cDNA– Reversely transcribed from mRNA

• Genomic sequences– Directly sequenced from DNA strings of

various species

• EST’s– a tiny portion of an entire gene derived from

mRNA

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Macromolecular structure databases

• Protein Data Bank (PDB) www.rcsb.org/pdb

• Nucleic Acids Database (NDB) http://ndbserver.rutgers.edu//

• PDBsum www.biochem.ucl.ac.uk/bsm/pdbsum

• CATHwww.biochem.ucl.ac.uk/bsm/cath

• SCOP http://scop.mrc-lmb.cam.ac.uk/scop/

• FSSP www.embl-ebi.ac.uk/dali/fssp

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Molecular interaction databases

• General– Biomolecular Interaction Network Database http://bioinfo.mshri.on.ca/cgi-bin/bind/dataman

– Molecular interactions Database (MINT) http://cbm.bio.uniroma2.it/mint/

• Protein-Protein interactions– Database of interacting proteins http://dip.doe-mbi.ucla.edu/

• Biochemical pathways– KEGG Metabolic Pathways http://www.genome.ad. jp/kegg

/metabolism.html

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Proteomics databases

• Yeast Proteome Database http://www.incyte

.com/sequence/proteome/databases/YPD.shtml

• SWISS-2DPAGEhttp://us.expasy.org/ch2d/

• TMIG-2DPAGEhttp://proteome.tmig.or.jp/2D/

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Genome databases

• Entrez genomes www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

• Ensemble genomes http://www.ensembl.org/

• HIV Sequence Database

http://hiv-web.lanl.gov/content/hiv-db/mainpage.html

• FlyBase http://flybase.bio.indiana.edu/

• COGs www.ncbi.nlm.nih.gov/COG

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Integrated databases

Increasing the value of information

• InterPro www.ebi.ac.uk/interpro

• Sequence retrieval system (SRS) www.expasy.ch/srs5

• Entrez www.ncbi.nlm.nih.gov/Entrez

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Entrez

Journals

UniGenePubMed Nucleotide

Protein

SNP

Genome

BooksProbeSet

OMIM

CDD

Taxonomy

3D Domains

UniSTS

PopSet

Structure

The (ever) Expanding Entrez System

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EBI services

• http://www.ebi.ac.uk/services/index.html

EBI

GenBankGenBank

DDBJDDBJ

EMBLEMBL

EMBLEMBL

Entrez

SRS

getentry

NIGNIGCIB

NCBI

NIHNIH

•Submissions•Updates •Submissions

•Updates

•Submissions•Updates

The International Sequence Database Collaboration

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A closer look at GenBank

• Maintained by NCBI

• Accessed through

Entrez

• Synchonized with

DDBJ and EMBL

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Sequence file formats

• Ideally – a stringent, easy to parse, specified format to facilitate the dissemination of information

• Reality – a plethora of coincidental and badly specified formats

• Different levels of information

• Some common formats– FASTA

– GenBank

– PHYLIP (PHYLIP package and others)

– Nexus (PAUP package, MacClade and others)

– Up and coming: XML

• Simple – sequence and name attribute

• Advanced – several attributes

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FASTA format

>gi|532319|pir|TVFV2E|TVFV2E envelope protein ELRLRYCAPAGFALLKCNDADYDGFKTNCSNVSVVHCTNLMNTTVTTGLLLNGSYSENRTQIWQKHRTSNDSALILLNKHYNLTVTCKRPGNKTVLPVTIMAGLVFHSQKYNLRLRQAWCHFPSNWKGAWKEVKEEIVNLPKERYRGTNDPKRIFFQRQWGDPETANLWFNCHGEFFYCKMDWFLNYLNNLTVDADHNECKNTSGTKSGNKRAPGPCVQRTYVACHIRSVIIWLETISKKTYAPPREGHLECTSTVTGMTVELNYIPKNRTNVTLSPQIESIWAAELDRYKLVEITPIGFAPTEVRRYTGGHERQKRVPFVXXXXXXXXXXXXXXXXXXXXXXVQSQHLLAGILQQQKNL LAAVEAQQQMLKLTIWGVK

http://www.ncbi.nlm.nih.gov/BLAST/fasta.html

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GenBank format

A verbose but very informative format

Contains much information in carefully specified format

Harder to parse than FASTA

http://www.ncbi.nlm.nih.gov/Sitemap/samplerecord.html

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eXtensible Markup Language (XML)

• Markup language for data-representation – derived from SGML, sib of HTML

• Stringent simple language with rigid rules

• Human readable and versatile

• Good parsers exists for multiple platforms

• The ability to design own Document Type Definitions that parsers can use to validate a

document permits complex data structures and grammars

• Examples of use for sequence data:

– NCBI GBSeqXML

– NCBI TinySeqXML

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Links

http://www.ncbi.nlm.nih.gov/Education/

http://www.infobiogen.fr/services/dbcat/

http://www.science.gmu.edu/~ntongvic/Bioinformatics/database.html

http://www.hgmp.mrc.ac.uk/GenomeWeb/prot-interaction.html

http://www.no.embnet.org/Programs/DB/srs.php3