Bioinformatics Databases

MV 2017
 Data in Bioinformatics
• DNA- Sequences of nucleotides (ATGC) that
contain information in the form of triplet codons
having specific reading frames and built-in control
segments
• RNA sequences (AUGC) mRNA, tRNA, hnRNA
• Protein sequences- Strings of Amino-acid
sequences (e. g., Aspartate, Glycine, Histidine,
Isoleucine, Leucine, Methionine, Serine,
Threonine, Valine, Phenyl alanine, Tyrosine)
• Structure data (Protein structure-primary
secondary, tertiary, Quaternary, 3D views)
• Images of 2D Gel electrophoresis
 Bioinformatics Databases
• Databases are convenient system to properly
store, search and retrieve any type of data
• Databases are different types based on nature of
information and manner (complexity) of data
storage
 Types of databases
Based on nature of information db are divided
into
• 1. Generalized db: DNA, Protein (e. g., NCBI)
– a. Sequence db: nucleotides or amino acids
– b. Structure db: structure of macromolecules
• 2. Specialized db: Expressed Sequence Tags
(EST), Single Nucleotide Polymorphisms (SNP)
Based on the manner of data storage, db are divided
into
1. Primary or abbreviated db: in original form, taken
as such from the source. Eg: GenBank, Swiss-Prot
2. Secondary db: value added db with derived
information from primary db
3. Composite db: combined primary db
Redundant and Non-redundant db: more than
one copy of each sequence
Boutique db: species specific sequence data
• Db entries composed of
– Core data: original sequence
– Supplementary data or annotation (source,
author, date, method used etc)

• Sequence formats
– PIR (Protein Information Resource)/NBRF(National
Biomedical Res. Foundation) - >P, >N
– FASTA (Fast Alignment) - >
– GDE (Genetic Data Environment) - %
 Primary Databases
• In original form, taken from the source
• Original submission by researcher
• Contents controlled by the submitter
• Data explosion in 1980s - so started many
repositories
1. Nucleic acid sequence db
2. Protein sequence db
3. Metabolite db
 Secondary databases
• Derivative db
• Result of analyses of sequences in the primary db
• Secondary db built up from primary db
• Secondary db analyzed in a variety of ways and
contain different information in different formats
• Contents of secondary db controlled by a third
party
• Eg: Prosite, Prints, Blocks
 Nucleic acid sequence databases
• Collection of nucleotide sequences
• Organize and distribute nucleotide sequences from
all available source
• In the form of a text file
• Can read by humans and computer
• Many dbs are assembled from several
publications, so overlapping fragments of
complete sequence
• First sequence - Yeast t-RNA with 77 bases in 1964
 NCBI
• National Centre for Biotechnology Information
• Established on November 4, 1988 as part of
the National Library of Medicine (NLM) at the
National Institute of Health (NIH), USA
• Headquarters in Bethesda, Maryland
• Legislation sponsored by Senator Claude
Pepper
 Services
• Pubmed
• Genbank
• BLAST
• Entrez
 GenBank
• GenBank ® is the NIH genetic sequence
database, an annotated collection of all
publicly available DNA sequences
• GenBank is part of the International
Nucleotide Sequence Database Collaboration
(INSDC) , which comprises the DNA DataBank
of Japan (DDBJ), the European Nucleotide
Archive (ENA), and GenBank at NCBI. These
three organizations exchange data on a daily
basis.
 International Nucleotide Sequence
Database Collaboration (INSDC)
• INSDC consist of
• 1. EMBL
• 2. DDBJ
• 3. GenBank
• Daily exchange of data
• The GenBank database is designed to provide
and encourage access within the scientific
community to the most up to date and
comprehensive DNA sequence information.
Therefore, NCBI places no restrictions on the
use or distribution of the GenBank data.
However, some submitters may claim patent,
copyright, or other intellectual property rights
in all or a portion of the data they have
submitted.
 What is in it?
• Annotated nucleotide sequences, including
mRNA sequences with coding regions,
segments of genomic DNA with a single gene
or multiple genes, and ribosomal RNA gene
clusters
• More than 100,000 organisms
• Aminoacid translations (CDS)
 EMBL
• The European Molecular Biology Laboratory (EMBL) is
a molecular biology research institution supported by
25 member states, four prospect and two associate
member states. EMBL was constituted in 1974 and is
an intergovernmental organisation funded by public
research money from its member states. Research at
EMBL is conducted by approximately 85 independent
groups covering the spectrum of molecular biology.
EMBL groups and laboratories perform basic research
in molecular biology and molecular medicine as well as
training for scientists, students and visitors.
 Stations
• The Laboratory operates from six sites: the
main laboratory in Heidelberg, and
outstations in Hinxton (the European
Bioinformatics Institute (EBI), in
England), Grenoble (France), Hamburg (Germa
ny), Monterotondo (near Rome)
and Barcelona (Spain).
 European Molecular Biology Laboratory
(EMBL)
• From European Bioinformatics Institute (EBI), UK
• Collect and assemble data from
-Direct author submission
-Genome sequencing groups
-Patent application
-Literature
• Goal - integrate nucleotide sequence data and
annotation into the wealth of bioinformatics
resources
• By cross reference and Sequence Retrieval System
(SRS) data can be viewed in 200 local stations
• 2494 completed genomes
 EMBL
• The roots of the EMBL-EBI lie in the EMBL
Nucleotide Sequence Data Library (now
known as EMBL-Bank), which was established
in 1980 at the EMBL laboratories in
Heidelberg, Germany and was the world's first
nucleotide sequence database.
• The original goal was to establish a central
computer database of DNA sequences, to
supplement sequences submitted to journals.
• The EMBL-EBI hosts a number of publicly open, free to use
life science resources, including biomedical databases,
analysis tools and bio-ontologies. These include:
• ArrayExpress - archive of gene expression experiments
• BioModels Database - a database of computational models
relevant to the life sciences
• BioStudies - a database that serves as a generic data
archive at EMBL-EBI for biomolecular datasets
• Chemical Entities of Biological Interest (ChEBI) - database
and ontology of molecular entities
• European Nucleotide Archive (ENA) - resource of
nucleotide sequencing information
• Ensembl project - genome databases for vertebrates and
other eukaryotic species (joint with Wellcome Trust Sanger
Institute)
• Europe PubMed Central - database offering free access to
collection of biomedical research literature
DNA Data Bank of Japan
• Currently, DDBJ Center is in operation at the
National Institute of Genetics (NIG) in
Mishima, Japan with endorsement of MEXT;
Japanese Ministry of Education, Culture,
Sports, Science and Technology.
• DDBJ Center is reviewed and advised by its
own advisory board, DNA Database Advisory
Committee (an outside committee of NIG),
and also by the advisory board to
INSDC, International Advisory Committee.
• Started in 1986
• It is located at the National Institute of
Genetics (NIG) in the Shizuoka prefecture of
Japan. It is also a member of the INSDC. It
exchanges its data with European Molecular
Biology Laboratory at the European
Bioinformatics Institute and with GenBank at
the National Center for Biotechnology
Information on a daily basis.
• These three databanks contain the same data
at any given time.
 Protein sequence databases
• SWISSPROT, PIR
• UniProtKB/Swiss-Prot is the manually
annotated and reviewed section of the
UniProt Knowledgebase (UniProtKB).
• It is a high quality annotated and non-
redundant protein sequence database, which
brings together experimental results,
computed features and scientific conclusions.
• Since 2002, it is maintained by the UniProt
consortium and is accessible via the UniProt
website.
 UniProtKB/Swiss-Prot
• UniProtKB/Swiss-Prot is the manually
annotated and reviewed section of the
UniProt Knowledgebase (UniProtKB).
It is a high quality annotated and non-
redundant protein sequence database, which
brings together experimental results,
computed features and scientific conclusions.
• Since 2002, it is maintained by the UniProt
consortium and is accessible via the UniProt
website.
 Swiss-Prot
• Established in 1986 by Dept. of Biochemistry, University of Geneva
• Maintenance by Swiss Institute of Bioinformatics (SIB) and EMBL

• Database composed of 2 parts

1. Core data - sequence reference and taxonomic details
2. Annotation - sequence variants, functions, 2o & 3o structures

• Provide high level annotation including functions of the protein

• Maintain high quality and structure - first choice for most research
purpose

• Swiss-Prot is supplemented by TrEMBL in 1996 - translated EMBL

• TrEMBL has 2 sections

1. SP-TrEMBL - data included in the Swiss-Prot from EMBL
2. REM-TrEMBL - data which are not included in the Swiss-Prot
• A well-defined manual curation process is
essential to ensure that all manually
annotated entries are handled in a consistent
manner. This process consists of 6 major
mandatory steps: (1) sequence curation, (2)
sequence analysis, (3) literature curation, (4)
family-based curation, (5) evidence
attribution, (6) quality assurance and
integration of completed entries. Curation is
performed by expert biologists using a range
of tools that have been iteratively developed
in close collaboration with curators.
 Protein Sequence Databases
1. PIR - Protein Information Resource
• Established in 1984 by National Biomedical
Research Foundation (NBRF), Washington DC
• Aim - identification and interpretation of protein
sequence information
• Investigating evolutionary relationship among
proteins
• Help to do search and similarity analysis
• Provide integrated environment for sequence
analysis between 3 units
 PIR - Protein Information Resource
• Established in 1984 by National Biomedical
Research Foundation (NBRF), Washington DC
• Aim - identification and interpretation of protein
sequence information
• Investigating evolutionary relationship among
proteins
• Help to do search and similarity analysis
• Provide integrated environment for sequence
analysis between 3 units
PIR is composed of 3 databases:
1. PSD - protein sequence database
2. NREF - Non-redundant reference database
3. iProClass - provides structural and functional
features of proteins

• PIR database split into 4 sections - differ in terms

of quality of data and levels of annotation provided
1. fully classified and annotated entries
2. preliminary entries, not thoroughly reviewed
3. unverified entries, not reviewed
4. genetically engineered sequences
Structure databases
 PDB

• Protein Data Bank

• The Protein Data Bank (PDB) is a crystallographic
database for the three-dimensional structural data of
large biological molecules, such
as proteins and nucleic acids. The data, typically
obtained by X-ray crystallography, NMR
spectroscopy, or, increasingly, cryo-electron
microscopy
 www.rcsb.org/
• The data is freely accessible on the Internet via
the websites of its member organisations (PDBe,
PDBj, and RCSB).
• The PDB is overseen by an organization called
the Worldwide Protein Data Bank, wwPDB.
• The PDB is a key resource in areas of structural
biology, such as structural genomics. Most major
scientific journals, and some funding agencies,
now require scientists to submit their structure
data to the PDB. Many other databases use
protein structures deposited in the PDB.
• Molecular graphics display, the Brookhaven
RAster Display (BRAD), is used to visualize
protein structures in 3-D.
• The file format initially used by the PDB was
called the PDB file format.
• PDB was initiated in 1968 with the help of
BRAD visualization of protein structure and X
ray crystallographic studies of proteins
• In October 1998, the PDB was transferred to
the Research Collaboratory for Structural
Bioinformatics (RCSB).
• In 2003, with the formation of the wwPDB,
the PDB became an international organization.
The founding members are PDBe (Europe),
RCSB (USA), and PDBj (Japan).
• Each of the three members of wwPDB can act
as deposition, data processing and
distribution centers for PDB data.
• The data processing refers to the fact that
wwPDB staff review and annotate each
submitted entry
INSULIN
NDB
• The Nucleic Acid Database (NDB; Berman et
al., 1992) was established in 1991 as a
resource for specialists in the field of nucleic
acid structure. Over the years, the NDB has
developed generalized software for
processing, archiving, querying and
distributing structural data for nucleic acid-
containing structures. The core of the NDB has
been its relational database of nucleic acid-
containing crystal structures.
• It allows researchers to perform comparative
analyses of nucleic acid-containing structures
selected from the NDB
• Structures available in the NDB include RNA and
DNA oligonucleotides with two or more bases
either alone or complexed with ligands, natural
nucleic acids such as tRNA and protein±nucleic
acid complexes. The archive stores both primary
and derived information about the structures
• The primary data include the crystallographic
coordinate data, structure factors and
information about the experiments used to
determine the structures, such as crystallization
information, data-collection and refinement
statistics.
 OMIM
• Online Mendelian Inheritance in Man
• A comprehensive, authoritative and timely
compendium of human genes and genetic
phenotypes
• The full-text, referenced overviews in OMIM
contain information on all known Mendelian
disorders and over 12,000 genes.
• Initiated in the early 1960s by Dr. Victor A. Mc
Kusick as a catalogue of Mendelian traits and
disorders, entitled Mendelian Inheritance in
Man
• 1995 internet version