Trykipedia: T.cruzi Semantics and Services enabled Problem Solving Environment
Trypanosoma cruzi is a protozoan parasite and a relative of other human pathogens that cause African sleeping sickness and leishmaniasis. Approximately 18 million people in Latin America are infected with this parasite, and as many as 40% of these are predicted to eventually suffer from Chagas disease, which is the leading cause of heart disease and sudden death in middle-aged adults in the region. Currently, there is a single manufactured drug for treatment of the infection; but this drug has severe side effects and is also carcinogenic. Diagnosis of the infection is poor and there are no vaccines for prevention of the infection. Moreover, T. cruzi presents a level of complexity that, though not unique, is substantial. br/ br/ Research in many biological systems, particularly those involving infectious agents, continues to experience an enormous increase in information with the sequencing of genomes, the use of expression profiling, and the completion of proteomic analyses. For example, annotated genomes and comparative analyses of two T. cruzi related kinetoplastids, Trypanosoma brucei ref Berriman M, G.E., Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu DC, Lennard NJ, Caler E, Hamlin NE, Haas B, Bohme U, Hannick L, Aslett MA, Shallom J, Marcello L, Hou L, Wickstead B, Alsmark UC, Arrowsmith C, Atkin RJ, Barron AJ, Bringaud F, Brooks K, Carrington M, Cherevach I, Chillingworth TJ, Churcher C, Clark LN, Corton CH, Cronin A, Davies RM, Doggett J, Djikeng A, Feldblyum T, Field MC, Fraser A, Goodhead I, Hance Z, Harper D, Harris BR, Hauser H, Hostetler J, Ivens A, Jagels K, Johnson D, Johnson J, Jones K, Kerhornou AX, Koo H, Larke N, Landfear S, Larkin C, Leech V, Line A, Lord A, Macleod A, Mooney PJ, Moule S, Martin DM, Morgan GW, Mungall K, Norbertczak H, Ormond D, Pai G, Peacock CS, Peterson J, Quail MA, Rabbinowitsch E, Rajandream MA, Reitter C, Salzberg SL, Sanders M, Schobel S, Sharp S, Simmonds M, Simpson AJ, Tallon L, Turner CM, Tait A, Tivey AR, Van Aken S, Walker D, Wanless D, Wang S, White B, White O, Whitehead S, Woodward J, Wortman J, Adams MD, Embley TM, Gull K, Ullu E, Barry JD, Fairlamb AH, Opperdoes F, Barrell BG, Donelson JE, Hall N, Fraser CM, Melville SE, El-Sayed NM., The genome of the African trypanosome Trypanosoma brucei. Science, 2005 Jul 15. 309(5733): p. 416-22. /ref and Leishmania major ref Ivens AC, P.C., Worthey EA, Murphy L, Aggarwal G, Berriman M, Sisk E, Rajandream MA, Adlem E, Aert R, Anupama A, Apostolou Z, Attipoe P, Bason N, Bauser C, Beck A, Beverley SM, Bianchettin G, Borzym K, Bothe G, Bruschi CV, Collins M, Cadag E, Ciarloni L, Clayton C, Coulson RM, Cronin A, Cruz AK, Davies RM, De Gaudenzi J, Dobson DE, Duesterhoeft A, Fazelina G, Fosker N, Frasch AC, Fraser A, Fuchs M, Gabel C, Goble A, Goffeau A, Harris D, Hertz-Fowler C, Hilbert H, Horn D, Huang Y, Klages S, Knights A, Kube M, Larke N, Litvin L, Lord A, Louie T, Marra M, Masuy D, Matthews K, Michaeli S, Mottram JC, Muller-Auer S, Munden H, Nelson S, Norbertczak H, Oliver K, O'neil S, Pentony M, Pohl TM, Price C, Purnelle B, Quail MA, Rabbinowitsch E, Reinhardt R, Rieger M, Rinta J, Robben J, Robertson L, Ruiz JC, Rutter S, Saunders D, Schafer M, Schein J, Schwartz DC, Seeger K, Seyler A, Sharp S, Shin H, Sivam D, Squares R, Squares S, Tosato V, Vogt C, Volckaert G, Wambutt R, Warren T, Wedler H, Woodward J, Zhou S, Zimmermann W, Smith DF, Blackwell JM, Stuart KD, Barrell B, Myler PJ., The genome of the kinetoplastid parasite, Leishmania major. Science, 2005 Jul 15. 309(5733): p. 436-42. /ref , and a whole organism (all life-cycle stages) proteome analysis of T. cruzi have been published ref Atwood, J.A., et al., The Trypanosoma cruzi Proteome, in Science 2005. p. 473 – 476. /ref . Data from other sequencing projects in T. cruzi, including ESTs ref Agüero F, Z.W., Weatherly DB, Mendes P, Kissinger JC, TcruziDB: an integrated, postgenomics community resource for Trypanosoma cruzi. Nucleic Acids Research, Jan 1 2006. 34(Database issue): p. D428-31. /ref , preexisting and ongoing expression profiling (DNA microarray ref Minning TA, B.J., Garcia GA, McGraw RA, Tarleton RL, Microarray profiling of gene expression during trypomastigote to amastigote transition in Trypanosoma cruzi. Mol Biochem Parasitol., 2003 Sep. 131(1): p. 55-64. /ref ) and proteome analyses are also available. These dynamic datasets, addressing different but logically related aspects, are distributed over multiple databases that undergo frequent additions and curation.
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Semantics and Services enabled Problem Solving Environment for Tcruzi Project
The Semantics and Services enabled Problem Solving Environment for T. cruzi project aims to utilize state-of-the-art semantic technologies for effective querying of multiple databases through creation of a suite of ontologies modeling multiple aspects of T. cruzi research domain. Trykipedia is a Wiki-based resource for the ontologies being created as part of this project: br/ br/
Parasite Life Cycle Ontology
We have completed the development of an ontology to model the life cycle stage details of T.cruzi and two related kinetoplastids, Trypanosoma brucei and Leishmania major. In addition to life cycle stages, the ontology also models necessary contextual details such as host information, vector information, strain and, anatomical location (refer to Figure 1). All the entities in the ontology are linked to each other by explicitly modeled named relationship that will enable software applications to accurately interpret data annotated with this ontology. For example, “Trypanosoma_cruzi→has_vector_organism(named relationship)→triatominae”. The parasite life cycle ontology is modeled in the World Wide Web consortium (W3C) Web Ontology Language (OWL) standard and currently has 41 classes and 5 properties with a description logic (DL) expressivity of ALU. The ontology, along with its Wiki-based resource page (refer to Figure 2) will be released for listing and public use at NCBO in the latter half of this month (February, 2009). We expect this ontology to replace the current “prototype” ontology modeling parasite life cycle (http://www.sanger.ac.uk/Users/mb4/PLO/) for which development effort has apparently been discontinued since 2002.
TcruziExperiri ontology
We have also completed the development of the TcruziExperiri ontology that models the transcriptome and gene-knockout phases of T.cruzi experiment protocols. The ontology comprehensively models the processes, instruments, parameters, and sample details (refer to Figure 3) that will be used to annotate experimental results with “provenance” metadata (derivation history of results). For example, given a drug selected sample (a sample that has been grown under selective drug pressure. source: TcruziExperiri ontology), details about the drug, drug concentration, the duration for the drug selection process, and the transfected sample used as input to the drug selection process are modeled in the ontology. This extensive provenance metadata modeled in this ontology will enable publication of results in journals, conferences with details of the method used to arrive at the result. TcruziExperiri currently has 71 classes and 15 properties with a DL expressivity of ALCHF(D) and incorporates concepts defined in Parasite Life Cycle ontology to maximize re-use of existing ontological resources.
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T.cruzi Resource Articles
table width=100%
tr valign=top
td
A
ul li Accession Number/li liAmastigote/li liAnatomical Location /li /ul
h3B/h3
ul
liBlood stream form/li
liBloodstream/li
/ul
h3C/h3
ul
liCell Cloning/li
liChagas disease/li
liCloned Sample/li
/ul
h3D/h3
ul
liDog/li
liDrug/li
liDrug Concentration/li
liDrug Resistant Plasmid/li
liDrug Selected Sample/li
liDrug Selection/li
/ul
h3E/h3
ul
liEpimastigote/li
/ul
h3G/h3
ul
liGene Knockout Protocol/li
liGenome/li
/ul
h3H/h3
ul
liHindgut/li
liHost organism/li
liHuman/li
liHuman African Trypanosomiasis/li
liHybridisation/li
/ul
h3K/h3
ul
liKinetoplastid/li
liKnockout Construct Plasmid/li
/ul
/td
td
h3K cont./h3
ul
liKnockout Plasmid/li
/ul
h3L/h3
ul
liLabelling/li
liLeishmania/li
liLeishmaniasis/li
liLifecycle stage/li
liLutzomyia/li
/ul
h3M/h3
ul
liMacrophage/li
liMedium/li
liMetacyclic/li
liMice/li
liMicroarray Analysis/li
liMicroarray Plate Reader/li
liMidgut/li
/ul
h3N/h3
ul
liNew World/li
liNucleated Cell/li
liNucleic Acid/li
/ul
h3O/h3
ul
liOld World/li
liOntology/li
liOrganism/li
/ul
h3P/h3
ul
liParasitic organism/li
liPhenotype/li
liPhlebotomus/li
liPlasmid/li
liPlasmid Construction/li
liPolymerase Chain Reaction/li
/ul
/td
td
h3P cont./h3
ul
liPrehybridisation/li
liProcyclic/li
liPromastigote/li
liPurity/li
/ul
h3S/h3
ul
liSalivary Gland/li
liSample/li
liSand fly/li
liSequence Extraction/li
liSignal Intensity/li
liSleeping sickness/li
liStrains/li
/ul
h3T/h3
ul
liTcruzi Sample/li
liTranscriptome Protocol/li
liTransfected Sample/li
liTransfection/li
liTransfection Buffer/li
liTransfection Machine/li
liTriatomine/li
liTrypanosoma brucei/li
liTrypanosoma cruzi/li
liTrypomastigote/li
liTsetse fly/li
/ul
h3V/h3
ul
liVector organism/li
/ul
/td
/tr
/table
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Publications
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References:references/
