1. The Penn Experience with MAGE-TAB John Brestelli Elisabetta Manduchi Junmin Liu Jonathan Schug Chris Stoeckert NCI MAGE Workshop Jan 24, 2008

2. http://www.cbil.upenn.edu/RAD/

3. Support diabetes research

4. Support research on protozoan parasites

5. MAGE-TAB Studies so far … Started with MAGE-Tab spec available in 2006 (i.e. before MAGE-Tab v1.0 finalized) and built a framework (MR_Ti) around it by the end of 2006. Have loaded 22 studies into RAD (our local database) using MAGE-TAB over the past year. MAGE-TAB generated from templates (original submissions) and from downloaded studies. Species covered: human, mouse, Plasmodium, Toxoplasma Applications covered: expression profiles, chromatin immunoprecipitation, genomic polymorphisms.

6. Example MAGE-TAB spreadsheet

8. Lessons Learned Positive response from data submittors for spreadsheets. –Provide examples and templates with areas to be filled in colored. –Pretty much use all fields except “release date” and “comment” –22 studies, 2 are hand-coded by biologists, 4 are generated by templates which are filled in by biologists. It is very useful from our data loading aspect. But it is hard for biologists to understand the format and manually generate without any help like providing templates. Ontology terms provided by curator –Menus were messy and hard to navigate (but probably could be overcome technically) Adaptable to non-array technologies –Final touches on a complicated Taqman study on ES cell differentiation protocols

9. Do MAGE-TAB templates have to follow MAGE-TAB specifications? Of course, but the biologists filling them out don’t need to know that!

10. MAGE-TAB Tools and Process Methods used for MAGE-Tab generation –Manually generate a MAGE-Tab –MAGE-Tab template then convert to MAGE-Tab –MAGE-ML, convert to MAGE-Tab using mage2tab developed by us. –GEO-Importer, MAGE-Tab converter (from ArrayExpress) Mage2graph: visualization Mage-checker: validation LoadMageDoc plugin

11. Handling MAGE docs in unified way processors validators translator O/R layer GUS DB mage doc Mage doc in other formats graph common objects ontology matrix

12. MR_Ti overview Reader Processor Validator Translator Study->submit Reporter Tester VO’ VO GusObj MagemlReader MageTabReader SoftReader BaseProcessor ProcessModule MergeTreatmentSerials NamingBioSamples NamingScans BaseValidator ValidationRule ProtocolHasMageType StudyDesignHasMageType AssayHasFactorValues make ServiceFactroy GUS Commit MR_Tilogger SqlReporter SqlTester Config.xml read-in use MR_TiException VoToGusTranslator VoToMageTab VoToDot

13. MAGE-TAB Tools and Process Initial contact with investigator/ Review publication Provide appropriate MAGE-TAB template Get filled in template Download SOFT files from GEO/ Review publication If Affymetrix, use ArrayExpress converter tool to generate MAGE-Tab; if cDNA array, in-house script to generate template. Review tab files and fill in protocols, experimental factors, ontology terms as needed. Validate, load, and check graph MAGE-ML files From ArrayExpress Convert to MAGE-Tab using mage2tab Convert to MAGE-Tab using template2tab

14. Details EPConDB 2904Survivin transgenic mice pancreatic islet profile (MAGE-ML) 2929Genome-wide location analysis of HNF Transcription Factors in Hepatocytes and Pancreatic Islets (MAGE-ML) 2944Sox4 null mice e12.5 pancreas (templates) 3021Neurogenin3 deficiency and Embryonic Pancreatic Gene Expression (SOFT) 3042Foxa2 controls vesicle docking and insulin secretion in mature beta-cells (generated by PIs) 3061Gene expression profiling of Nkx2-2 Mutant and Wild-Type - e12.5 and e13.5 Pancreata(templates) 3100Gene expression profiling in the endocrine pancreas (templates) 3121Gene expression profiling of MafA, MafB, and MafA/MafB Mutants in E18.5 pancreas (templates) T1Dbase 3144Expression data from NOD-scid vs B6-scid pancreas, submandibular glands, & lacrimal glands (SOFT) 3203 Gene expression in PBMCs from children with diabetes (SOFT) PlasmoDB (SOFT) 21 Molecular mechanism for switching of P.falciparum invasion pathways into human erythrocytes 22 P.falciparum strain 3D7, SIR2 knockout 23 Invasion by P. falciparum merozoites suggests a hierarchy of molecular interactions 29 Regulation of sexual development of Plasmodium by translational repression. 51 Expression profile of 3D7 clones 3D7AH1S2 and 3D7S8.4 at ring, trophozite and schizont stages. 52 CD36 panned clones 55 Identification of genome wide gene copy number polymorphisms in Plasmodium falciparum 64 Tetracyclines Specifically Target the Apicoplast of the Malaria Parasite Plasmodium falciparum 85 Whole genome analysis of mRNA decay in P. falciparum 161 Plasmodium falciparum W2/Dd2 Day 8 gametocytes ToxoDB (generated by PIs) 42 Expression profiling of the 3 archetypal T. gondii lineages 101 Effects of Glucose Starvation in Toxoplasma gondii