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Transcript
Bioinformatics Ayesha M. Khan Spring 2013 2 Lec-3 Introduction to databases If we are to derive the maximum benefit from the deluge of sequence information, we must deal with it in a concerted way by doing the following: Establish Maintain Disseminate the information contained in databases 3 Introduction to Databases Lec-3 • Databases are effectively electronic filing cabinets, a convenient and efficient method of storing vast amounts of information. • Central, shareable resources Many different types of databases, depending on -Nature of information being stored -Manner of data storage 4 Lec-3 Primary & Secondary databases • Primary and secondary databases are used to address different aspects of sequence analysis, because they store different levels of protein sequence information Primary or derived databases Primary databases: experimental results directly into database Secondary databases: results of analysis of primary databases Aggregate of many databases /Composite databases Links to other data items Combination of data Consolidation of data 5 Lec-3 Primary sequence databases • Early 1980’s • Nucleic acidEMBL (Europe), GenBank (USA), DDBJ (Japan) • Protein PIR, SWISS-PROT, TrEMBL, NRL-3D 6 EMBL: Lec-3 EMBL is the nucleotide sequence database from European Bioinformatics Institute (EBI) It has sequences from: direct author submissions, genome sequencing groups, scientific literature and patent applications. DDBJ: DNA databank of Japan, produced maintained and distributed at the National Institute of Genetics. GenBank: DNA database from National Biotechnology Information (NCBI). Center for 7 Lec-3 Principal requirements of a database The principal requirements on the public data services are: • Data quality - data quality has to be of the highest priority. However, because the data services in most cases lack access to supporting data, the quality of the data must remain the primary responsibility of the submitter. • Supporting data - database users will need to examine the primary experimental data, either in the database itself, or by following cross-references back to networkaccessible laboratory databases. • Deep annotation - deep, consistent annotation comprising supporting and ancillary information should be attached to each basic data object in the database. • Timelines - the basic data should be available on an Internet-accessible server within days (or hours) of publication or submission. • Integration - each data object in the database should be cross-referenced to representation of the same or related biological entities in other databases. Data services should provide capabilities for following these links from one database or data service to another. 8 Lec-3 Exercise Look for a gene of your interest in the three primary nucleic acid databases: compare the information given in each one of them. 9 Primary Sequence Database Amino Acid Nucleic Acid e.g. GenBank, EMBL, DDBJ SwissProt and PIR Lec-3 Secondary Sequence Database Protein Domains & Families Metabolic Pathways e.g. RefSeq and Conserved Domain Database (CDD) within NCBI Sequencing centers Researchers Literature Flowchart of sequence data from labs and literature to primary sequence database and subsequent secondary databases 10 Always remember that: • The data within primary databases is as reliable as the data submitted. • This depends primarily on the methods used to produce it. • Regardless of who obtains the sequence data, nucleic acid and amino acid sequencing results are subject to errors. Lec-3 11 Protein Sequence databases Lec-3 • The protein sequence database was developed at the National Biomedical Research Foundation (NBRF) • Early 1960’s by Margaret Dayhoff to investigate evolutionary relationships among proteins • 1988 onwards, maintained collectively by: Protein Information Resource (PIR) at NBRF, International Protein Information Database of Japan (JIPID), and the Martinsried Institute for Protein Sequences (MIPS). 12 Examples of molecular sequence types in NCBI records Lec-3 Type Genome Sequence Tagged site (STS) Description A unique segment of DNA that occurs only once in a genome and marks a particular location. Can be generated from genomic DNA or cDNA. Pieces of a genome that are compiled from a DNA or cDNA Draft sequences library. Usually large collection of contigs and are in the process of being ordered and catalogued. Genome The complete genome of an organism. 13 Type Chromosome Locus Contig Description Lec-3 A known location on a chromosome for a particular gene or collection of genes that codes for a specific function. A contiguous segment of a chromosome made by joining overlapping clones or sequences. Chromosome The whole sequence of a single chromosome. 14 Gene Type Description Domain A discrete portion of a protein assumed to fold independently of the rest of the protein and which possesses its own function. Complete CDS A complete coding sequence for a protein. Gene Whole gene sequence for a protein Lec-3 15 mRNA Type Description Expressed sequence tag (EST) A partial sequence of cDNA in mRNA form from either the 5’ or 3’ end of a gene sequence. Lec-3 Complementary A cDNA sequence in mRNA form. DNA sequence (cDNA) Complete CDS A complete mRNA sequence for a protein coding region. 16 Protein Sequence databases Lec-3 • SWISS-PROT Started in 1986-University of Geneva and EMBL It is now maintained by Swiss Institute of Bioinformatics (SIB) and EBI/EMBL • TrEMBL Started in 1996-Follows SWISS-PROT format and contains translations of coding sequences in EMBL. It also provides: synthetic sequences, short amino acid fragments, and codons that do not encode real proteins. 17 Lec-3 Composite protein sequence databases A database that merges a variety of different primary sources. They obviate the need to interrogate multiple resources. It can eliminate identical sequence copies, or eliminate both identical and highly similar sequences.