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Paul Schofield

Reader in Biomedical Informatics
Tel: +44 (0)1223 333878, Fax: +44 (0)1223 333840, E-mail: ps@mole.bio.cam.ac.uk

The main focus of the group is the use of mouse models to understand human diseases and gene function, particularly fetal-overgrowth disorders such as Beckwith-Wiedemann syndrome. We are involved in the development of approaches and informatics tools to capture and analyse phenotypic data from mice, particularly in the area of histopathology, and are working with the International Knockout Mouse Consortium and the International Mouse Phenotyping Consortium on data capture, integration and analysis.

Ontology development and phenotype informatics tools
Comparing phenotypes between species potentially provides invaluable insights into the pathobiology and etiology of human disease. Phenotypic characterisation of, for example, mouse and zebrafish mutants can provide information that can be used to prioritise gene lists derived from human genome-wide association studies, allow the dissection of loci involved in copy number-variation lesions, and provide functional validation of disease gene candidates, as well as insights into basic biological processes. The ability to cross the species divide has long been a thorny problem, as human and model organism phenotypes are described using different formal ontologies and conceptual approaches. To address this, we are working to develop a series of ontologies and tools that use those ontologies, allowing the seamless integration of phenotypic data between species.

Mammalian pathology ontology – MPATH
George Gkoutos, John Sundberg, Michael Gruenberger

MPATH, the mammalian pathology ontology was initially designed to describe the pathological features of histological slides of mouse lesions in Pathbase, a database of mutant mouse pathology. The ontology has been developed further since and now covers all classes of pathological lesion, and used in combination with the appropriate anatomy ontology and qualifiers from the phenotype and trait ontology, PATO, can be used to describe any histopathological lesion in mammals. The most recent version of MPATH can be obtained from Google Code or the Open Biological and Biomedical Ontologies (OBO) web site.

Phenomenet
George Gkoutos, Robert Hoehndorf

We have developed a semantic approach to integrating phenotype ontologies, Phenomenet, which uses formal definitions of ontology classes to generate equivalences between phenotypes in species-specific ontologies. These formal definitions are generated using the Phenotype and Trait ontology, PATO, together with multi-species or species-agnostic ontologies, such as MPATH, and the Gene Ontology, permitting bridging between the ontologies. Use of the full semantic information in these ontologies provides a powerful way to integrate and query phenotypic information. Phenomenet has been made available on the Phenome Browser.

Collaborators
We work closely on ontology development with Dr Peter Robinson (Human Phenotype Ontology), Prof Michael Ashburner (Dept Genetics, Cambridge), Prof Monte Westerfield (University of Oregon), and Prof Suzi Lewis (Lawrence Berkeley Laboratory), and have long term collaborations with Prof John Sundberg (The Jackson Laboratory).

Work on radiobiology legacy databases and community resources is the result of long-term, ongoing collaborations with Dr Bernd Grosche of the German Federal Office for Radiation Protection, and Prof Mike Atkinson and Dr Soile Tapio, of the Institute of Radiation Biology, Helmholtz Zentrum München.

Funding
Informatics work in the Group is currently funded by the BBSRC, NIH and the European Commission.

Selected recent papers
Kohler, S., S. C. Doelken, C. J. Mungall, S. et . al (2013). "The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data." Nucleic Acids Res. Nov 11. [Epub ahead of print]

Hoehndorf, R., J. M. Hancock, N. W. Hardy, et al. (2013). "Analyzing gene expression data in mice with the Neuro Behavior Ontology." Mamm Genome. Nov 1. [Epub ahead of print]

Hoehndorf, R., T. Hiebert, N. W. Hardy, et . al. (2013). "Mouse model phenotypes provide information about human drug targets." Bioinformatics. Nov 14. [Epub ahead of print]

Schofield, P. N., J. P. Sundberg, B. A. Sundberg, C. McKerlie and G. V. Gkoutos (2013). "The mouse pathology ontology, MPATH; structure and applications." J Biomed Semantics 4(1): 18.

Hoehndorf, R., P. N. Schofield and G. V. Gkoutos (2013). "An integrative, translational approach to understanding rare and orphan genetically based diseases." Interface Focus 3(2): 20120055.

Hoehndorf, R., N. W. Hardy, D. Osumi-Sutherland, S. Tweedie, P. N. Schofield and G. V. Gkoutos (2013). "Systematic analysis of experimental phenotype data reveals gene functions." PLoS One 8(4): e60847.

Doelken, S. C., S. Kohler, C. J. Mungall, et al. (2013). "Phenotypic overlap in the contribution of individual genes to CNV pathogenicity revealed by cross-species computational analysis of single-gene mutations in humans, mice and zebrafish." Dis Model Mech 6(2): 358-372.

Gkoutos, G. V., P. N. Schofield and R. Hoehndorf (2012). "The neurobehavior ontology: an ontology for annotation and integration of behavior and behavioral phenotypes." Int Rev Neurobiol 103: 69-87.

Gkoutos, G. V., P. N. Schofield and R. Hoehndorf (2012). "The Units Ontology: a tool for integrating units of measurement in science." Database (Oxford) 2012: bas033.

Gkoutos, G. V., P. N. Schofield and R. Hoehndorf (2012). "Computational tools for comparative phenomics: the role and promise of ontologies." Mamm Genome 23(9-10): 669-679.

Schofield, P. N., R. Hoehndorf and G. V. Gkoutos (2012). "Mouse genetic and phenotypic resources for human genetics." Hum Mutat 33(5): 826-836.

Chen, C. K., C. J. Mungall, G. V. Gkoutos, S. C. Doelken, S. Kohler, B. J. Ruef, C. Smith, M. Westerfield, P. N. Robinson, S. E. Lewis, P. N. Schofield and D. Smedley (2012). "MouseFinder: Candidate disease genes from mouse phenotype data." Hum Mutat 33(5): 858-866.

Hoehndorf, R., A. Oellrich, D. Rebholz-Schuhmann, P. N. Schofield and G. V. Gkoutos (2012). "Linking PharmGKB to phenotype studies and animal models of disease for drug repurposing." Pac Symp Biocomput: 388-399.