AAGTGCCACTGCATAAATGACCATGAGTGGGCACCGGTAAGGGAGGGTGATGCTATCTGGTCTGAAG. Protein 3D structure. sequence. primary. Interactions Mutations

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1 Introduction to Databases Lecture Outline Shifra Ben-Dor Irit Orr Introduction Data and Database types Database components Data Formats Sample databases How to text search databases What units of information do we deal with in bioinformatics? SNPs Nucleotide sequence Genes mrna AAGTGCCACTGCATAAATGACCATGAGTGGGCACCGGTAAGGGAGGGTGATGCTATCTGGTCTGAAG DNA Sequence Pathways Protein primary sequence RNA Protein Structure Evolution Interactions Mutations Protein 3D structure Protein Function Acts as a tumor suppressor in many tumor types. induces growth arrest or apoptosis depending on the physiological circumstances or cell type, but both activities are involved in tumor suppression. Involved in the transport of chloride ions. Defects in CFTR are the cause of cystic fibrosis. It is the most common genetic disease in the caucasian population, with a prevalence of about 1 in 2000 live births. cf, an autosomal recessive disorder, is a common generalized disorder of exocrine gland function All of these have databases and tools that were created to work with them What do we want from databases? Information retrieval from sequence databases Biological databases contain enormous amounts of data. Databases need to be well annotated. Databases need to be easily searched. Data found in databases should be easily retrieved. Data in databases should be in standard formats.

2 Integrated Information Retrieval Accession Number A Database breast cancer 1, early onset breast cancer 1, early onset Many databases contain logical relations between specific entries. One interface - connecting many biological databases. For example: a database that connects between protein sequence, protein domain, protein structure and reference databases. (Interpro) Another example: Connection between references, protein sequence, DNA sequence, and structure databases. (Entrez) Fields tumor protein p53 Chromosomal location: 17p13.1 DNA sequence: mrna sequence: brain - liver - lung - Protein sequence: Protein function: Protein structure: Interacts with genes: PDB 1OLG, 1OLH, 1SAE , , Entries External links Internal links Core Data and Annotation Databases generally have (at least) two types of data: Core data: The data the database was generated to organize Annotation: Extra information that rounds out our picture of the core data For example in a genome database, the sequence is the core data, and the location of genes is the annotation Database Issues Printed journals vs. databases Direct submission to databases (e.g. GenBank, GDB, PDB) Archival vs. curated databases Databases that publish experimental results of large genomic centers. Public vs. private databases. Database scope For Example: Classification of Genomic Databases Information source Information type Many genomes One Genome One Subject One Gene Direct submission from scientific community Scientific literature Genome center s experimental results Other databases Mapping Sequence & annotation Protein structure & function Variations Comparative genomics gene networks Database search free text field-specific sequence-based Database output text graphics dynamic User Interface

3 Data Formats Fasta Format There are many data formats used for sequences (both nucleic and amino acid) Fasta Format GenBank Format EMBL Format GCG Format Simplest format Least information Starts with a > and sequence name on one line The sequence in plain text follows >OB2T2 GTGACAACATGTACAGCTGTGAGCGGTGTAAGAAGCTGCGGAACGGAGTGAAGTACTGCA AAGTCCTGCGGTTGCCCGAGATCCTGTGCATTCACCTAAAGCGCTTTCGGCACGAGGTGA TGTACTCATTCAAGATCAACAGCCACGTCTCCTTGCCCTCGAGGGGCTCGACCTGCGCCC CTTCCTTGCCAAGGAGTGCACATCCCAGATCACCACCTACGACCTCCTCTCGGTCATCTG CCACCACGGCACGGCAGGCA >TNRC_HUMAN P36941 (tumor necrosis factor c receptor) MLLPWATSAPGLAWGPLVLGLFGLLAASQPQAVPPYASENQTCRDQEKEYYEPQHRICCS RCPPGTYVSAKCSRIRDTVCATCAENSYNEHWNYLTICQLCRPCDPVMGLEEIAPCTSKR KTQCRCQPGMFCAAWALECTHCELLSDCPPGTEAELKDEVGKGNNHCVPCKAGHFQNTSS PSARCQPHTRCENQGLVEAAPGTAQSDTTCKNPLEPLPPEMSGTMLMLAVLLPLAFFLLL ATVFSCIWKSHPSLCRKLGSLLKRRPQGEGPNPVAGSWEPPKAHPYFPDLVQPLLPISGD VSPVSTGLPAAPVLEAGVPQQQSPLDLTREPQLEPGEQSQVAHGTNGIHVTGGSMTITGN IYIYNGPVLGGPPGPGDLPATPEPPYPIPEEGDPGPPGLSTPHQEDGKAWHLAETEHCGA TPSNRGPRNQFITHD >TNRC_MOUSE P50284 lymphotoxin-beta receptor precursor MRLPRASSPCGLAWGPLLLGLSGLLVASQPQLVPPYRIENQTCWDQDKEYYEPMHDVCCS RCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTSDR KAECRCQPGMSCVYLDNECVHCEEERLVLCQPGTEAEVTDEIMDTDVNCVPCKPGHFQNT SSPRARCQPHTRCEIQGLVEAAPGTSYSDTICKNPPEPGAMLLLAILLSLVLFLLFTTVL ACAWMRHPSLCRKLGTLLKRHPEGEESPPCPAPRADPHFPDLAEPLLPMSGDLSPSPAGP PTAPSLEEVVLQQQSPLVQARELEAEPGEHGQVAHGANGIHVTGGSVTVTGNIYIYNGPV LGGTRGPGDPPAPPEPPYPTPEEGAPGPSELSTPYQEDGKAWHLAETETLGCQDL >TNR1_RAT P22934 tumor necrosis factor receptor 1 precursor (p60) MGLPIVPGLLLSLVLLALLMGIHPSGVTGLVPSLGDREKRDNLCPQGKYAHPKNNSICCT KCHKGTYLVSDCPSPGQETVCEVCDKGTFTASQNHVRQCLSCKTCRKEMFQVEISPCKAD MDTVCGCKKNQFQRYLSETHFQCVDCSPCFNGTVTIPCKEKQNTVCNCHAGFFLSGNECT PCSHCKKNQECMKLCLPPVANVTNPQDSGTAVLLPLVIFLGLCLLFFICISLLCRYPQWR PRVYSIICRDSAPVKEVEGEGIVTKPLTPASIPAFSPNPGFNPTLGFSTTPRFSHPVSST PISPVFGPSNWHNFVPPVREVVPTQGADPLLYGSLNPVPIPAPVRKWEDVVAAQPQRLDT ADPAMLYAVVDGVPPTRWKEFMRLLGLSEHEIERLELQNGRCLREAHYSMLEAWRRRTPR HEATLDVVGRVLCDMNLRGCLENIRETLESPAHSSTTHLPR Genbank sequence format NM_ Homo sapiens crys...[gi: ] LOCUS NM_ bp mrna PRI 15-MAY-2001 DEFINITION Homo sapiens crystallin, alpha A (CRYAA), mrna. ACCESSION NM_ VERSION NM_ GI: KEYWORDS. SOURCE human. ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 1114) AUTHORS Jaworski,C.J. and Piatigorsky,J. TITLE A pseudo-exon in the functional human alpha A- crystallin gene Genbank sequence format JOURNAL Nature 337 (6209), (1989) MEDLINE PUBMED REFERENCE 2 (bases 1 to 1114) AUTHORS Jaworski,C.J. TITLE A reassessment of mammalian alpha A-crystallin sequences using DNA sequencing: implications for anthropoid affinities of tarsier

4 FEATURES Location/Qualifiers source /organism="homo sapiens" /db_xref="taxon:9606" /chromosome="21" /map="21q22.3" gene /gene="cryaa" /note="crya1" /db_xref="locusid:1409" /db_xref="mim:123580" misc_feature /note="crystallin; Region: Alpha crystallin A chain" CDS /gene="cryaa" /note="human alphaa-crystallin; crystallin, alpha-1" /codon_start=1 /db_xref="locusid:1409" /db_xref="mim:123580" /product="crystallin, alpha A" /protein_id="np_ " /db_xref="gi: " /translation="mdvtiqhpwfkrtlgpfypsrlfdqffgeglfeydllpfl SSTISPYYRQSLFRTVLDSGISEVRSDRDKFVIFLDVKHFSP EDLTVKVQDDFVEIHGKHNERQDDHGYISREFHRRYRLPS NVDQSALSCSLSADGMLTFCGPKIQTGLDATHAERAIPVSR EEKPTSAPSS" misc_feature /note="hsp20; Region: Hsp20/alpha crystallin family" polya_signal BASE COUNT 183 a 400 c 309 g 222 t ORIGIN 1 acactgcgct gcccagaggc cccgctgact cctgccagcc tccaggtccc cgtggtacca 61 aagctgaaca tggacgtgac catccagcac ccctggttca agcgcaccct ggggcccttc 121 taccccagcc ggctgttcga ccagtttttc ggcgagggcc tttttgagta tgacctgctg 181 cccttcctgt cgtccaccat cagcccctac taccgccagt ccctcttccg caccgtgctg 241 gactccggca tctctgaggt tcgatccgac cgggacaagt tcgtcatctt cctcgatgtg 301 aagcacttct ccccggagga cctcaccgtg aaggtgcagg acgactttgt ggagatccac 361 ggaaagcaca acgagcgcca ggacgaccac ggctacattt cccgtgagtt ccaccgccgc 421 taccgcctgc cgtccaacgt ggaccagtcg gccctctctt gctccctgtc tgccgatggc 481 atgctgacct tctgtggccc caagatccag actggcctgg atgccaccca cgccgagcga 541 gccatccccg tgtcgcggga ggagaagccc acctcggctc cctcgtccta agcaggcatt 601 gcctcggctg gctcccctgc agccctggcc catcatgggg ggagcaccct gagggcgggg 661 tgtctgtctt cctttgcttc ccttttttcc tttccacctt ctcacatgga atgagggttt 721 gagagagcag ccaggagagc ttagggtctc agggtgtccc agaccccgac accggccagt 781 ggcggaagtg accgcacctc acactccttt agatagcagc ctggctcccc tggggtgcag 841 gcgcctcaac tctgctgagg gtccagaagg agggggtgac ctccggccag gtgcctcctg 901 acacacctgc agcctccctc cgcggcgggc cctgcccaca cctcctgggg cgcgtgaggc 961 ccgtggggcc ggggcttctg tgcacctggg ctctcgcggc ctcttctctc agaccgtctt 1021 cctccaaccc ctctatgtag tgccgctctt ggggacatgg gtcgcccatg agagcgcagc 1081 ccgcggcaat caataaacag caggtgatac aagc // Revised: October 24, ID A standard; DNA; FUN; 581 BP. AC AJ279484; SV AJ DT 14-JAN-2000 (Rel. 62, Created) DT 14-JAN-2000 (Rel. 62, Last updated, Version 2) DE Unidentified ascomycota sp. 4/ S rrna gene and ITS 1 and 2 KW 5.8S ribosomal RNA; 5.8S rrna gene; internal transcribed spacer 1; KW internal transcribed spacer 2; ITS1; ITS2. OS ascomycota sp. 4/97-9 OC Eukaryota; Fungi; Ascomycota. RN [1] RP RA Wirsel S.G.R.; RT ; RL Submitted (21-DEC-1999) to the EMBL/GenBank/DDBJ databases. RL Wirsel S.G.R., Fakultaet fuer Biologie, Universitaet Konstanz, RL Universitaetsstr. 10, Konstanz 78434, Germany. RN [2] RA Wirsel S.G.R., Leibinger W., Mendgen K.W.; RT "Genetic diversity of fungi associated with common reed (Phragmites RT australis)"; RL Unpublished. FH Key Location/Qualifiers FH FT source FT /db_xref="taxon:112223" FT /organism="ascomycota sp. 4/97-9" FT /isolate="4/97-9"

5 FT misc_feature FT /note="internal transcribed spacer 1, ITS1" FT rrna FT /gene="5.8s rrna" FT /product="5.8s ribosomal RNA" FT misc_feature FT /note="internal transcribed spacer 2, ITS2" SQ Sequence 581 BP; 132 A; 164 C; 145 G; 140 T; 0 other; ccatttagag gaagtaaaag tcgtaacaag gtctccgttg gtgaaccagggagggatc 60 ttacgagagt gtcaccactc ccaacccact gtttacctac ccgtccaccg tgcttcggca 120 ggcagtcctg tgggacaggg cctcgccccc ctccgggggg tgcctgccgc Each line in the entry begins with a two-character line code, which indicates the type of information contained in the line. The currently used line types, along with their respective line codes, are listed below: ID - identification (begins each entry; 1 per entry) AC - accession number (>=1 per entry) SV - sequence version (1 per entry) DT - date (2 per entry) DE - description (>=1 per entry) KW - keyword (>=1 per entry) OS - organism species (>=1 per entry) OC - organism classification (>=1 per entry) OG - organelle (0 or 1 per entry) RN - reference number (>=1 per entry) RC - reference comment (>=0 per entry) RP - reference positions (>=1 per entry) RX - reference cross-reference (>=0 per entry) RA - reference author(s) (>=1 per entry) RT - reference title (>=1 per entry) RL - reference location (>=1 per entry) DR - database cross-reference (>=0 per entry) FH - feature table header (0 or 2 per entry) FT - feature table data (>=0 per entry) CC - comments or notes (>=0 per entry) - spacer line (many per entry) SQ - sequence header (1 per entry) bb - (blanks) sequence data (>=1 per entry) // - termination line (ends each entry; 1 per entry ) GCG Format Has space for comments and space for data, separated by two dots.. Can contain full sequence data like GenBank or EMBL Has a minimum of sequence name, length, date, type (nucleic or amino acid) and checksum!!na_sequence 1.0 5B3.seq Length: 744 March 18, :43 Type: N Check: TCTAGAGGAG AYATYGTWAT GACCCAGTCT CCATCCTCCC TGAGTGTGTC 51 AGCAGGAGAG AAGGTCACTA TGAGCTGCAA GTCCAGTCAG AGTCTGTTAA 101 ACAGTAGAAA TCAAAAGAAC TACTTGGCCT GGTACCAGCA GAAACCAGGA 151 CAGCCTCCTA AACTTTTGAT CTACGGGGTA TTTATTAGGG ATTCTGGGGT 201 CCCTGATCGC TTCACAGGCA GTGGATCTGG AACCGATTTC ACTCTTACCA 251 TCAGCAGTGT GCAGGCTGAA GACCTGGCAG TTTATTACTG TCAGAATGAT 301 CATATTTATC CGTACACGTT CGGAGGGGGC ACWAAGCTGG AAATTAAAGG 351 GTCGACTTCC GGTAGCGGCA AATCCTCTGA AGGCAAAGGT SAGGTSCAGC 401 TGCAGGAGTC TGGACCTGGC CTGGTGAAGC CTTCCCAGTC TCTGTCCCTC 451 ACCTGCTCTG TCACTGGTTA CTCAATCACC AGTGGTTATG CCTGGAACTG 501 GATCCGGCAG TTTCCAGGAA ACAAACTGGA GTGGATGGGC TACATAAGCT 551 ACAGTGGTTT CACTAGCTAC AACCCATCTC TCAGAAGTCG AATCTCTTTC