Towards a repor+ng structure for cancer therapy experiments Alejandra Gonzalez-­‐Beltran1, May Yong2, Richard Begent2 1Computa+onal and Systems Medicine & Department of Computer Science 2Cancer Ins+tute University College London, London, United Kingdom Recording of Experiments GIATE Repor+ng Use Cases and Mapping to GIATE ontology GIATE: a repor+ng guideline for therapy experiments Guidelines on Informa+on about Therapy Experiments (GIATE) is a reporCng guideline for recording informa+on about therapy experiments. GIATE was built as a checklist of data elements, where each element is a Common Data Elements (CDE) from the Na+onal Cancer Ins+tute (NCI) cancer Data Standards Registry and Repository (caDSR) and some extra CDEs that were not present in caDSR. See [1,2] for more details. AnCbody-­‐Directed Enzyme Prodrug Therapy (ADEPT) is an an+body-­‐mediated method of delivering a therapeu+c agent to tumour sites with high specificity. MFE-­‐CP is a fusion protein of an an+body and an enzyme. When administered, the an+body binds onto carcinoembryonic an+gen (CEA), which is expressed on tumour sites. This fusion protein is then carefully cleared from the rest of the body, leaving the fusion protein bound to CEA. A prodrug is administered, the enzyme part of the fusion protein func+ons to ac+vate the cytotoxicity ability of the prodrug to kill the tumour cells. Phase 1 Phase 2 Prodrug Enzyme: CPCG2 MFECP1 Recording and repor+ng experiments efficiently – their design, context and results – is crucial for the advancement of biomedical research as it: •  enables reproducCon of the experiments •  allows for well-­‐grounded comparisons •  supports reuse and integraCon of data • facilitates reliable analysis due to improved sta+s+cal power of the data An+body: MFE-­‐23 Glutamate An+gen: CEA Tumour cell Cell death Schema+c diagram of the principle of ADEPT from [2] has subclass has individual hasAgent hasAgentComponent GIATEConcept Therapeu+c Target Therapeu+c Procedure Therapeu+c Agent Therapeu+cAgent Component Model CellularModel Protein ClinicalModel MolecularModel An+body AnimalModel GIATE ontology We have created a minimum informa+on checklist, as a guideline of what are the key elements to consider when repor+ng a therapy experiment. This checklist is based on the CDEs described above. We recommend using the checklist while performing the experiment, for publica+ons and for educa+onal purposes. GIATE checklist is registered with the Minimum InformaCon for Biological and Biomedical InvesCgaCons (MIBBI). Addi+onally, we have defined a simple spreadsheet format to facilitate the data input process. GIATE representa+on of the ADEPT therapy[3,4], focusing on the therapy design and showing three models in which the therapy was applied to, using the GIATE ontology to indicate semanCcs: hasAnatomicStructure hasTarget performedInModel GIATE minimum informa+on checklist & data format Xenograa Ac+vatedCHSepharose An+Carcinoembryonic An+gen Adept LS174T Glucarpidase MFE-­‐23 Phase1ClinicalModel XenograaNudeMouse ADEPT instances Mustard Prodrug Carcinoembryonic An+gen Therapy design Models Conclusions and Future Work We presented the GIATE repor+ng structure Our objec+ve is to provide appropriate tools for scien+st to use with GIATE, so that scien+st can record their experiments as part of their everyday work. The data generated will cons+tute a GIATE knowledge based. Addi+onally, we plan to link the GIATE knowledge base to external resources, such as those provided by the Linked Data Cloud. GIATE metadata Experimental design Molecular model Cellular model Animal model Clinical model References
[1] M Yong, B Tolner, S Nagl, et al: Data standards for minimum informa+on collec+on for an+body therapy experiments. Protein Eng Des Sel. 22 (3), 221-­‐224 (2009) [2] M. Yong, R. Begent: Best use of experimental data in cancer informa+cs. Future Oncology. October 2010, Vol. 6, No. 10, Pages 1551-­‐1562 [3] SK Sharma, RB Pedley, J Bha+a et al: Sustained tumor regression of human colorectal cancer xenograas using a mul+func+onal mannosylated fusion protein in an+body-­‐directed enzyme prodrug therapy. Clin Cancer Res 11, 814-­‐825 (2005) [4] A Mayer, RJ Francis, SK Sharma, B Tolner et al: A phase I study of single administra+on of an+body-­‐directed enzyme prodrug therapy with the recombinant an+-­‐carcinoembryonic an+gen an+body-­‐enzyme fusion protein MFECP1 and a bis-­‐iodo phenol mustard prodrug. Clin Cancer Res 12, 6509-­‐6516 (2006) AGB is funded by the MRC grant G0802528 “ Transla+onal Research Ini+a+ve”. MY and RB are funded by the UCL Experimental Cancer Medicine Centre, UCL and KCL Comprehensive Cancer Imaging Centre.