Databases & Data banks

“It is a capital mistake to theorize before one has data”.

Sir Arthur Conan Doyle (1859-1930),

A scandal in Bohemia

Banche Dati Biologiche

informazioni e dati di letteratura,

sperimentali e in silico.

Banche Dati Biologiche

Struttura delle Banche Dati Banche Dati Primarie Banche Dati Specializzate e Risorse

Genomiche Interoperabilità fra le Banche Dati Sistemi di Retrieval

Struttura delle Banche dati

elemento biologico centrale

"entry" della banca dati

Struttura delle Banche datiEntry name e Accession Number

Informazioni associate Ontologia: una formale descrizione delle entità e delle relazioni intercorrenti fra esse

Struttura delle Banche datiFormato flat-file

Tabella relazioni

Colonna =attributiRiga=record o k--tupla

Fig.2.3. Relational database. A table (relation) is a set and the three basic table operations shown here are extensions of the standard set operations.

DB deduttivi

Fig.2.4. Deductive database. The data in the family tree is represented and manipulated in a deductive database, which consists of a relational database and a logic programming

Object oriented

Fig. 2.5. Object-oriented database. The concept of similarity is implemented in an object-oriented database wich incorporates many different aspects of genes.

Banche Dati DNA e RNA

Le Banche Dati di sequenze di acidi nucleici sono

spesso Banche Dati Primarie in quanto

contengono solo informazioni generiche con un

minimo di informazione da associare alla

sequenza per identificarla dal punto di vista

specie-funzione.

Banche Dati Primarie(DNA)

1980 EMBL 1982 GenBank

1986 DDBJ

EMBL Data LibraryRelease 110 – Dec 2011

230,021,806 Entries

376,471,768,435 Nucleotides

Banche Dati Primarie(Proteine)

SWISS-PROT

TrEMBL

PIR

Importance of reference protein sequence databases

• Completeness and minimal redundancy

A non redundant protein sequence database, with maximal coverage including splice isoforms, disease variant and PTMs.

Low degree of redundancy for facilitating peptide assignments

• Stability and consistency Stable identifiers and consistent nomenclature

Databases are in constant change due to a substantial amount of work to improve their completeness and the quality of sequence annotation

• High quality protein annotation

Detailed information on protein function, biological processes, molecular interactions and pathways cross-referenced to external source

Summary of protein sequence databases

Database Description Species

UniProtKB Expertly curated section (UniProtKB/Swiss-Prot) and computer-annotated section (UniProtKB/TrEMBL); minimum level of redundancy; high level of integration with other databases; stable identifiers; diversity of sources including large scale genomics, small scale cloning and sequencing, protein sequencing, PDB, predicted sequences from Ensembl and RefSeq

Many

UniRef100 Assembled from UniProtKB, Ensembl and RefSeq; merges 100% identical sequences; stable identifiers

Many

Ensembl Predictions using automated genome annotation pipeline; explicitly linked to nucleotide and protein sequences; stable reference; merge their annotations with Vega annotations at transcript level; extensive quality checks to remove erroneous gene models ; high level of integration with other databases

Over 50 Eukaryotic genomesEnsembl Genomes: Metazoa, Plants and Fungi, Protists, Bacteria and Archaea

RefSeq NCBI creates from existing data; ongoing curation; non-redundant; explicitly linked nucleotide and protein sequences; stable reference; high level of integration with other databases

Limited to fully sequenced organisms

Entrez protein (NCBInr) Assembled from GenBank and RefSeq coding sequence translations and UniProt KB ; annotations extracted from source curated databases; high degree of sequence redundancy

Many

Updated from Nesvizhskii, A. I., and Aebersold, R. (2005) Interpretation of shotgun proteomic data: the protein inference problem. Mol. Cell. Proteomics. 4,1419–1440l

UniProtKB

Master headline

UniProt Knowledgebase:

2 sections

1. UniProtKB/Swiss-Prot Non-redundant, high-quality manual annotation - reviewed

2. UniProtKB/TrEMBL Redundant, automatically annotated - unreviewed

www.uniprot.org

Sequence Sequence features

Ontologies

ReferencesNomenclature

Splice variants

Annotations

UniProtKB

Manual annotation of UniProtKB/Swiss-Prot

Master headline

Splice variants

Master headline

Identification of amino acid variants

..and of PTMs

… and also

Master headline

Protein nomenclature

Master headline

Master headline

Controlled vocabularies used whenever possible…

Annotation - >30 defined fields

1 Evidence at protein levelThere is experimental evidence of the existence of a protein

(e.g. Edman sequencing, MS, X-ray/NMR structure, good quality protein-protein interaction , detection by antibodies)

2 Evidence at transcript levelThe existence of a protein has not been proven but there is

expression data (e.g. existence of cDNAs, RT-PCR or Northern

blots) that indicates the existence of a transcript.

3 Inferred from homologyThe existence of a protein is likely because orthologs exist in closely

related species

4 Predicted

5 Uncertain

Sequence evidence

Type of evidence that supports the existence of a protein

Manual annotation of the human proteome(UniProtKB/Swiss-Prot)

• A draft of the complete human proteome has been available in UniProtKB/Swiss-Prot since 2008

• Manually annotated representation of 20,242 protein coding genes with ~ 36,000 protein sequences - an additional 38,484 UniProtKB/TrEMBL form the complete proteome set

• Approximately 63,000 single amino acid polymorphisms (SAPs), mostly disease-linked

• 80,000 post-translational modifications (PTMs)• Close collaboration with NCBI, Ensembl, Sanger Institute

and UCSC to provide the authoritative set to the user community

Master headline

Searching UniProt – Simple Search

• Text-based searching• Logical operators ‘&’ (and), ‘|’

Master headline

Searching UniProt – Advanced Search

Master headline

Searching UniProt – Search Results

Each linked to the UniProt entry

Master headline

Searching UniProt – Search Results

Master headline

Searching UniProt – Search Results

Inter-operabilità fra le Banche dati

Di fondamentale importanza e’ introdurre nel

disegno delle banche dati i meccanismi di

cross-referencing che consentono di navigare

fra i database anche se dislocati su siti tra di

loro remoti

A link-based integration of molecular biology databases in the DBGET/LinkDB system at GenomeNet (http://www.genome.ad.jp/). The lines indicate thet the cross-references are given by the original databases.