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BioAssay Ontology (BAO )

BioAssay Ontology (BAO ). chemical biology. PubChem. domain. caspase activity. standards. cheminformatics. nomenclature. activity. semantic. enzyme reporter. fluorescence. viability. binding based. programming. data sets. knowledge. search. screening. technology. end point.

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BioAssay Ontology (BAO )

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  1. BioAssay Ontology (BAO) chemical biology PubChem domain caspase activity standards cheminformatics nomenclature activity semantic enzyme reporter fluorescence viability binding based programming data sets knowledge search screening technology end point PDSP thesauri article object XML enzyme substrate based versioning high-thoughput screening (HTS) natural language software classification polysemes biological pathways Beta-Lactamase Induction dehydrogenase activity specificity annotation subject indexing schemes properties GFP induction Fluorogenic substrate Stephan Schürer, PhD ChemBank chemical probes information exchange servers ATP Luciferin Coupled classes synonyms search tool controlled vocabulary ICBO, Buffalo, July 30 2011 biological assay disease networks biomedical knowledge structure concepts meta-data taxonomies small molecule subject headings cyclic AMP redistribution RDF calcium redistribution sschurer@med.miami.edu OWL novel chemical tools indexing pharmaceutical semantic web library authorized terms structural biology individuals homographs tags energy transfer

  2. Background for BioAssayOntology High-throughput screening • One of the most important approaches to find novel entry points for drug discovery programs • Historically in pharmaceutical companies • Since ~2005, massive NIH effort (MLI) to make HTS accessible to public sector research • PubChem is the major repository of HTS data • More recently: EU-OpenScreen project

  3. Motivation for BioAssayOntology Large public screening data sets PubChem, ChEMBL, PDSP, ChemBank, Binding DB • Lack of standardized assay annotations • No standardized endpoint names or formats • Data is rarely re-used(!) • Common queries cannot be asked • Analysis across different data sets is difficult • Integration with other databases is difficult • No knowledge model for assays and screening results

  4. Queries the Ontology should be able to answer Identify inhibitors of kinases in biochemical assays. Identify compounds active in multiple luciferase reporter gene assays. Identify compounds active in cell viability assays and organize by cell lines and assay types. Identify active compounds in assays related to pathway X. …

  5. Leverage the aggregated corpus of publically available HTS data to infer molecular mechanism of actions (MMOA) of small molecule perturbagensin biological model systems. Schüreret al. “BioAssay Ontology Annotations Facilitate Cross-Analysis of Diverse High-throughput Screening Data Sets” J Biomol Screen2011 (16), 415-426.

  6. BAO Products and Resources • BAOSearch Software (beta):http://baosearch.ccs.miami.edu • Query, explore, download BAO-annotated PubChem content • Some semantic search capabilities • Project Website and Wiki with relevant materials and documentation:http://www.bioassayontology.org/http://www.bioassayontology.org/wiki

  7. Questions / Discussion points • Application / user focus vs. “universal” ontologies • Efficiency vs. “realism” of representations • Rapid application development • Orthogonal ontologies vs. Ontology mapping • Universal “realism” vs. domain or application-specific • Chemical bond: 2D structure graph, 3D rule based, molecular mechanics, semi-empirical, up-initio QM • Disease • Virtual world

  8. Questions / Discussion points • Collaborative ontology development • Collaborative vs. individual effort • Control over development and focus / application focus • Rapid application development • Quality • Aligning BAO to upper level ontology (BFO) • Benefits vs. required resources • Do upper level ontologies matter for specialized applications?

  9. Questions / Discussion points • Aligning BAO with OBI • Some level of overlap • OBI: process-oriented (model the investigation) • BAO: purpose of categorization and analysis of HTS data • BAO model becomes more complex if based on OBI • How do we do it practically • Define missing assays to OBI and MIREOT back? • Quick term templates (QTT)? • Define our relations as short-cut relationships (using RO)?

  10. Additional slides

  11. BAO-facilitated Example for Analysis (Luciferase Assays) Details in: Schürer et al. “BioAssay Ontology Annotations Facilitate Cross-Analysis of Diverse High-throughput Screening Data Sets” J Biomol Screen2011 (16), 415-426.

  12. Most promiscuous reporter gene compounds Assay Count Panel Assay Single Conc Other Conc-response

  13. Luciferase Enzyme Inhibitors • Generally cytotoxic Most promiscuous reporter gene compounds Compounds Promiscuity Index 1 0 0.2 ATP SC ATP DR Viability SC Viability DR Luciferin SC Luciferin DR Reporter SC Reporter DR Enz Activ SC Enz Activ DR

  14. Examples: Cytotoxic Series Daunorubicin Cluster Reporter PCIdx: 0.56 Cluster Reporter Active: 58 Cluster Viability PCIdx: 0.64 Cluster Viability Active 27 Cluster Reporter PCIdx: 0.48 Cluster Reporter Active: 23 Cluster Viability PCIdx: 0.45 Cluster Viability Active 10 Emetine Cluster Reporter PCIdx: 0.41 Cluster Reporter Active: 29 Cluster Viability PCIdx: 0.57 Cluster Viability Active 13

  15. Examples: Luciferase Inhibitor Series Cluster Size: 6 Cluster Reporter PCIdx: 0.61 Cluster Reporter Active: 101 Cluster EnzActivity PCIdx: 0.58 Cluster EnzActivity: 15 Cluster Size: 5 Cluster Reporter PCIdx: 0.46 Cluster Reporter Active: 77 Cluster EnzActivity PCIdx: 0.58 Cluster EnzActivity: 14 Cluster Size: 4 Cluster Reporter PCIdx: 0.38 Cluster Reporter Active: 52 Cluster EnzActivityPCIdx: 0.61 Cluster EnzActivity: 11 Schürer et al. “BioAssay Ontology Annotations Facilitate Cross-Analysis of Diverse High-throughput Screening Data Sets” J Biomol Screen2011(16), 415-426.

  16. BAO Project: Three major components • Development of the Bioassay Ontology • Annotation of assays and assay results(content curation) • Development of software tools

  17. BAO design to describe assays

  18. Application of BAO: BAO Search Software

  19. http://baosearch.ccs.miami.edu/baosearch/

  20. BAO: Concept Search

  21. Biochemical Assays with IC50 < 1 mM

  22. Chemical structure search

  23. BAO Products and Resources • BioAssayOntology (NCBO bioportal and project site):http://bioportal.bioontology.org/ontologies/45410http://www.bioassayontology.org/visualize/ • Terminology / annotations for biochemical assays: http://www.bioassayontology.org/>Assay Annotation Template • Over 1000 BAO-annotated assays from PubChem (available in BAOSearch)

  24. Acknowledgements • SamindaAbeyruwan • Uma Vempati • Magdalena Przydzial • KunieSakurai • Robin Smith • YuanyuanJia • Caty Chung • Chris Mader • AmarKoleti • NakulDatar • SreeharshaVenkatapuram • FelimonGayanilo • Mark Southern • UbboVisser • Vance Lemmon • MitsunoriOgihara • Nick Tsinoremas http://bioassayontology.org sschurer@med.miami.edu

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