1 Middleware for In silico Biology Phillip Lord

2 UK e-Science Pilot Project. Oct 2001 – April £3.4 million. £0.4 million studentships. Newcastle Nottingham Manchester Southampton Hinxton Sheffield

3 Data-intensive bioinformatics ID MURA_BACSU STANDARD; PRT; 429 AA. DE PROBABLE UDP-N-ACETYLGLUCOSAMINE 1-CARBOXYVINYLTRANSFERASE DE (EC ) (ENOYLPYRUVATE TRANSFERASE) (UDP-N-ACETYLGLUCOSAMINE DE ENOLPYRUVYL TRANSFERASE) (EPT). GN MURA OR MURZ. OS BACILLUS SUBTILIS. OC BACTERIA; FIRMICUTES; BACILLUS/CLOSTRIDIUM GROUP; BACILLACEAE; OC BACILLUS. KW PEPTIDOGLYCAN SYNTHESIS; CELL WALL; TRANSFERASE. FT ACT_SITE BINDS PEP (BY SIMILARITY). FT CONFLICT S -> A (IN REF. 3). SQ SEQUENCE 429 AA; MW; 02018C5C CRC32; MEKLNIAGGD SLNGTVHISG AKNSAVALIP ATILANSEVT IEGLPEISDI ETLRDLLKEI GGNVHFENGE MVVDPTSMIS MPLPNGKVKK LRASYYLMGA MLGRFKQAVI GLPGGCHLGP RPIDQHIKGF EALGAEVTNE QGAIYLRAER LRGARIYLDV VSVGATINIM LAAVLAEGKT IIENAAKEPE IIDVATLLTS MGAKIKGAGT NVIRIDGVKE LHGCKHTIIP DRIEAGTFMI

4 Web Service (Grid Service) communication fabric AMBIT Text Extraction Service Provenance Personalisation Event Notification Gateway Service and Workflow Discovery myGrid Information Repository Ontology Mgt Metadata Mgt Work bench TavernaTalisman Native Web Services SoapLab Web Portal Legacy apps Registries Ontologies FreeFluo Workflow Enactment Engine OGSA-DQP Distributed Query Processor Bioinformaticians Tool Providers Service Providers Applications Core services External services Service Stack Views Legacy apps GowLab

5 Williams-Beuren Syndrome Microdeletion ** Chr 7 ~155 Mb ~1.5 Mb 7q11.23 GTF2I RFC2CYLN2 GTF2IRD1 NCF1 WBSCR1/E1f4H LIMK1ELNCLDN4CLDN3STX1A WBSCR18 WBSCR21 TBL2BCL7BBAZ1B FZD9 WBSCR5/LAB WBSCR22 FKBP6POM121 NOLR1 GTF2IRD2 C-cen C-midA-cen B-mid B-cen A-midB-telA-telC-tel WBSCR14 WBS SVAS STAG3 PMS2L Block A FKBP6T POM121 NOLR1 Block C GTF2IP NCF1P GTF2IRD2P Block B Patient deletions CTA-315H11 CTB-51J22 Gap Physical Map

6 WBS Workflows: GenBank Accession No GenBank Entry Seqret Nucleotide seq (Fasta) GenScanCoding sequence ORFs prettyseq restrict cpgreport RepeatMasker ncbiBlastWrapper sixpack transeq 6 ORFs Restriction enzyme map CpG Island locations and % Repetative elements Translation/sequence file. Good for records and publications Blastn Vs nr, est databases. Amino Acid translation epestfind pepcoil pepstats pscan Identifies PEST seq Identifies FingerPRINTS MW, length, charge, pI, etc Predicts Coiled-coil regions SignalP TargetP PSORTII InterPro PFAM Prosite Smart Hydrophobic regions Predicts cellular location Identifies functional and structural domains/motifs Pepwindow? Octanol? ncbiBlastWrapper URL inc GB identifier tblastn Vs nr, est, est_mouse, est_human databases. Blastp Vs nr RepeatMasker Query nucleotide sequence ncbiBlastWrapper Sort for appropriate Sequences only Pink: Outputs/inputs of a service Purple: Taylor-made services Green: Emboss soaplab services Yellow: Manchester soaplab services Grey: Unknowns RepeatMasker

7

8 Semantic discovery Query-ontology – discovering workflows and services described in the registry by building a query in Taverna. A common ontology is used to annotate and query. Look for all workflows that accept an input of semantic type nucleotide sequence. Aim to have semantic discovery over public view on the Web.

9 Semantic Discovery View annotations on workflow Pedro data capture tool Drag a workflow entry into the explorer pane and the workflow loads. Drag a service/ workflow to the scavenger window for inclusion into the workflow

10 Workflow annotation Adding structured metadata to a workflow registration to enable others to discover and reuse it more effectively. E.g. what semantic type of input does it accept.

AC Homo sapiens BAC clone CTA-315H11 from 7, complete sequence AC Homo sapiens BAC clone RP11-622P13 from 7, complete sequence AL Human DNA sequence from clone RP11-553N16 on chromosome 1, complete sequence AL Homo sapiens chromosome 21 segment HS21C AL Human chromosome 14 DNA sequence BAC R-775G15 of library RPCI-11 from chromosome 14 of Homo sapiens (Human), complete sequence BX Homo sapiens mRNA; cDNA DKFZp686G08119 (from clone DKFZp686G08119) AC Homo sapiens 12q22 BAC RPCI11-256L6 (Roswell Park Cancer Institute Human BAC Library) complete sequence AK Homo sapiens cDNA FLJ45040 fis, clone BRAWH AC Homo sapiens chromosome 17, clone RP11-104J23, complete sequence AL Human DNA sequence from clone RP4-715N11 on chromosome 20q Contains two putative novel genes, ESTs, STSs and GSSs, complete sequence AC Homo sapiens BAC clone RP11-731I19 from 2, complete sequence AC Homo sapiens chromosome 15, clone RP11-342M21, complete sequence AL Human DNA sequence from clone RP11-461K13 on chromosome 10, complete sequence AC Homo sapiens PAC clone RP3-368G6 from X, complete sequence AC Homo sapiens chromosome 4 clone B200N5 map 4q25, complete sequence AF Homo sapiens chromosome 21q22.3 PAC 171F15, complete sequence >gi| |gb|AC | Homo sapiens BAC clone CTA-315H11 from 7, complete sequence AAGCTTTTCTGGCACTGTTTCCTTCTT CCTGATAACCAGAGAAGGAAAAGATC TCCATTTTACAGATGAG GAAACAGGCTCAGAGAGGTCAAGGCT CTGGCTCAAGGTCACACAGCCTGGGA ACGGCAAAGCTGATATTC AAACCCAAGCATCTTGGCTCCAAAGC CCTGGTTTCTGTTCCCACTACTGTCAG TGACCTTGGCAAGCCCT GTCCTCCTCCGGGCTTCACTCTGCAC ACCTGTAACCTGGGGTTAAATGGGCT CACCTGGACTGTTGAGCG urn:lsid:taverna:datathing:15..BLAST_Report rdf:type urn:lsid:taverna:datathing:13..similar_sequences_to.. nucleotide_sequence rdf:type service invocation..created_by workflow invocation workflow definition experiment definition project person group service description organisation..described_by..run_during..invocation_of..part_of..works_for..part_of..author..run_for AB..masked_sequence_of..filtered_version_of Relationship BLAST report has with other items in the repository Other classes of information related to BLAST report Provenance tracking

12 Using IBM’s Haystack GenBank record Portion of the Web of provenance Managing collection of sequences for review

13 Acknowledgements myGrid is an EPSRC funded UK eScience Program Pilot Project Particular thanks to the other members of the Taverna project,

14 my Grid People Core Matthew Addis, Nedim Alpdemir, Tim Carver, Rich Cawley, Neil Davis, Alvaro Fernandes, Justin Ferris, Robert Gaizaukaus, Kevin Glover, Carole Goble, Chris Greenhalgh, Mark Greenwood, Yikun Guo, Ananth Krishna, Peter Li, Phillip Lord, Darren Marvin, Simon Miles, Luc Moreau, Arijit Mukherjee, Tom Oinn, Juri Papay, Savas Parastatidis, Norman Paton, Terry Payne, Matthew Pockock Milena Radenkovic, Stefan Rennick- Egglestone, Peter Rice, Martin Senger, Nick Sharman, Robert Stevens, Victor Tan, Anil Wipat, Paul Watson and Chris Wroe. Users Simon Pearce and Claire Jennings, Institute of Human Genetics School of Clinical Medical Sciences, University of Newcastle, UK Hannah Tipney, May Tassabehji, Andy Brass, St Mary’s Hospital, Manchester, UK Postgraduates Martin Szomszor, Duncan Hull, Jun Zhao, Pinar Alper, John Dickman, Keith Flanagan, Antoon Goderis, Tracy Craddock, Alastair Hampshire Industrial Dennis Quan, Sean Martin, Michael Niemi, Syd Chapman (IBM) Robin McEntire (GSK) Collaborators Keith Decker