* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Sequencing the World of Possibilities for Energy & Environment
Survey
Document related concepts
Ancestral sequence reconstruction wikipedia , lookup
Western blot wikipedia , lookup
Protein moonlighting wikipedia , lookup
Bisulfite sequencing wikipedia , lookup
Molecular evolution wikipedia , lookup
Protein structure prediction wikipedia , lookup
DNA sequencing wikipedia , lookup
Homology modeling wikipedia , lookup
Protein adsorption wikipedia , lookup
Two-hybrid screening wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Protein–protein interaction wikipedia , lookup
Genomic library wikipedia , lookup
Transcript
Sequencing the World of Possibilities for Energy & Environment Information Sources for Genomics Konstantinos Mavrommatis Genome Biology Program [email protected] MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Databases Databases used for the analysis of biological molecules. Databases contain information organized in a way that allows users/researchers to retrieve and exploit it. Why bother? Store information. Organize data. Predict features (genes, functions ...). Predict the functional role of a feature (annotation). Understand relationships (metabolic reconstruction). MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Overview Sequence databases Primary (contain “raw” data) Nucleotide Protein Secondary (processed information) Genes Proteins Classification databases Sequence classification Function classification Other methods Other specialized databases MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Primary nucleotide databases EMBL/GenBank/DDBJ (http://www.ncbi.nlm.nih.gov/,http://www.ebi.ac.uk/embl) Archive containing all sequences from: genome projects sequencing centers individual scientists patent offices The sequences are exchanged between the three centers on a daily basis. Database is doubling every 10 months. Sequences from >140,000 different species. 1400 new species added every month. Year 2004 2005 2006 2007 2008 Base pairs 44,575,745,176 56,037,734,462 69,019,290,705 83,874,179,730 99,116,431,942 Sequences 40,604,319 52,016,762 64,893,747 80,388,382 98,868,465 MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Primary protein sequence databases Contain coding sequences derived from the translation of nucleotide sequences GenBank Valid translations (CDS) from nt GenBank entries. UniProtKB/TrEMBL (1996) Automatic CDS translations from EMBL. TrEMBL Release 40.3 (26-May-2009) contains 7,916,844 entries. MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Errors in databases There are a lot of errors in the primary sequence databases: In the sequences themselves: Sequencing errors. Cloning vectors sequences. For the annotations, the free submission of entries results to: Inaccuracies, omissions, and even mistakes. Inconsistencies between some fields. MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Redundancy Redundancy is a major problem. Entries are partially or entirely duplicated: e.g. 20% of vertebrate sequences in GenBank. { { { Partial and complete sequence duplications MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Overview Sequence databases Primary (contain “raw” data) Nucleotide Protein Secondary (processed information) Genes Proteins Classification databases Sequence classification Function classification Other methods Other specialized databases MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment NCBI Derivative Sequence Data Curators RefSeq TATAGCCG AGCTCCGATA CCGATGACAA Labs Genome Assembly TATAGCCG TATAGCCG TATAGCCG TATAGCCG GenBank UniGene Algorithms MGM workshop. 19 Oct 2010 RefSeq Sequencing the World of Possibilities for Energy & Environment Curated transcripts and proteins. reviewed by NCBI staff. Model transcripts and proteins. generated by computer algorithms. Assembled Genomic Regions (contigs). Chromosome records. MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Secondary protein databases Uniprot/SWISS-PROT (1986) (http://ca.expasy.org/spro) a curated protein sequence database high level of annotation (such as the description of the function of a protein, its domains structure, post-translational modifications, variants, etc.) a minimal level of redundancy high level of integration with other databases MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Overview Sequence databases Primary (contain “raw” data) Nucleotide Protein Secondary (processed information) Genes Proteins Classification databases Sequence classification Function classification Other methods Other specialized databases MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Classification databases Groups (families/clusters) of proteins based on… Overall sequence similarity. Local sequence similarity. Presence / absence of specific features (active site, signal peptides… ). Structural similarity. ... These groups contain proteins with similar properties. Specific function, enzymatic activity. General function. Evolutionary relationship. … MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Overall sequence similarity MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Clusters of orthologous groups (COGs) COGs were delineated by comparing protein sequences encoded in 43 complete genomes representing 30 major phylogenetic lineages. Each Cluster has representatives of at least 3 lineages A function (specific or broad) has been assigned to each COG. http://www.ncbi.nlm.nih.gov/COG/ MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Profiles & Pfam A method for classifying proteins into groups exploits region similarities, which contain valuable information (domains/profiles). These domains/profiles can be used to detect distant relationships, where only few residues are conserved. MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Regions similarity MGM workshop. 19 Oct 2010 Pfam Sequencing the World of Possibilities for Energy & Environment http://pfam.sanger.ac.uk HMMs of protein alignments (local) for domains, or global (cover whole protein) MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment TIGRfam Full length alignments. Domain alignments. Equivalogs: families of proteins with specific function. Superfamilies: families of homologous genes. HMMs http://www.tigr.org/TIGRFAMs/ MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment KEGG orthology MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Composite pattern databases To simplify sequence analysis, the family databases are being integrated to create a unified annotation resource – InterPro Release 28.0 (Aug 10) contains 20837entries Central annotation resource, with pointers to its satellite dbs http://www.ebi.ac.uk/interpro/ MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment * It is up to the user to decide if the annotation is correct * MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment ENZYME MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment ENZYME http://ca.expasy.org/enzyme/ MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment KEGG Contains information about biochemical pathways, and protein interactions. http://www.kegg.com MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Overview Sequence databases Primary (contain “raw” data) Nucleotide Protein Secondary (processed information) Genes Proteins Classification databases Sequence classification Function classification Other methods Other specialized databases MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Sequencing projects GOLD Information for ongoing and finished (meta)genomic projects. Information about the metadata of genomes and metagenomic samples. http://www.genomesonline.org MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Literature search PubMed http://www.ncbi.nlm.nih.gov/Pubmed MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Specialized databases There is a large number of databases devoted to specific organisms. For some model organisms there are often concurrent systems. These databases are associated to sequencing or mapping projects. MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Other specialized databases Signal transduction, regulation, protein-protein interactions Gene 3D structures expression TRANSFAC (Transcription Factor database) GXD PDB(Mouse (Protein Gene Data Expression Bank) Database) BRITE (Biomolecular Relations in Information Transmission and The MMDB Stanford (Molecular Microarray Modelling Database Data Expression database) Base) Mapping DIP (DatabaseNRL_3D of Interacting Proteins) (Non-Redundant Library of GDB (Genome Data Base) 3D Structures) BIND (Biomolecular Interaction Network database) EMG (Encyclopedia of Mouse Genome) SCOP (Structural Classification of BioCarta MGD (Mouse Genome Database) Proteins) Biochemical pathways INE (Integrated Rice Genome Explorer) Polymorphism KLOTHO (Biochemical Compounds Declarative database) Protein quantification ALFRED (Allelesystem) Frequency Database) BRENDA (enzyme information SWISS-2DPAGE Molecular interactions LIGAND (similar to Enzyme but with more information for substrates) PDD (Protein Disease Database) DIP (Database of Interacting proteins) Gene order and co-occurrence Sub2D (B. subtilis 2D Protein Index) BIND (Biomolecular Interaction STRING Network Database) MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment List of databases http://www.oxfordjournals.org/nar/database/c MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Databanks interconnection Blocks MIMMAP REBASE PDBFINDER ALI PROSITEDOC OMIM ProDom PROSITE SWISSNEW ENZYME DSSP SWISSDOM HSSP FSSP GenBank PDB MOLPROBE SWISS-PROT NRL_3D ECDC EPD YPDREF PMD EMBL YPD EMNEW TFSITE TrEMBLNEW ProtFam FlyGene TrEMBL PIR TFACTOR Not all databases are updated regularly. Changes of annotation in one database are not reflected in others. MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Concluding remarks We have main archives (Genbank), and currated databases (Refseq, SwissProt), and protein classification database (COG, Pfam), and many, many more… They help predict the function, or the network of functions. Systems that integrate the information from several databases, visualize and allow handling of data in an intuitive way are required MGM workshop. 19 Oct 2010 Sequencing the World of Possibilities for Energy & Environment Thank you for your attention. MGM workshop. 19 Oct 2010