New approaches to the representation and analysis of phenotype knowledge in human diseases and their animal models

P. N. Schofield, J. P. Sundberg, R. Hoehndorf, G. V. Gkoutos
2011 Briefings in Functional Genomics  
The systematic investigation of the phenotypes associated with genotypes in model organisms holds the promise of revealing genotype^phenotype relations directly and without additional, intermediate inferences. Large-scale projects are now underway to catalog the complete phenome of a species, notably the mouse. With the increasing amount of phenotype information becoming available, a major challenge that biology faces today is the systematic analysis of this information and the translation of
more » ... search results across species and into an improved understanding of human disease. The challenge is to integrate and combine phenotype descriptions within a species and to systematically relate them to phenotype descriptions in other species, in order to form a comprehensive understanding of the relations between those phenotypes and the genotypes involved in human disease. We distinguish between two major approaches for comparative phenotype analyses: the first relies on evolutionary relations to bridge the species gap, while the other approach compares phenotypes directly. In particular, the direct comparison of phenotypes relies heavily on the quality and coherence of phenotype and disease databases. We discuss major achievements and future challenges for these databases in light of their potential to contribute to the understanding of the molecular mechanisms underlying human disease. In particular, we discuss how the use of ontologies and automated reasoning can significantly contribute to the analysis of phenotypes and demonstrate their potential for enabling translational research. Paul N. Schofield is Senior Lecturer in Anatomy. His expertise is in mammalian genetics and bioinformatics. He works on the control of mammalian pre-natal growth and the development of biomedical ontologies to relate human disease to mouse models. John P. Sundberg's research focuses on the biology and pathobiology of hair and skin using the mouse as a model system, and the role of papillomaviruses in the genesis of skin cancers and related diseases. In addition, he integrates large-scale pathological phenotyping with public access databases. Robert Hoehndorf received his PhD at Leipzig University and the Max Planck Institute for Evolutionary Anthropology. The focus of his research is the application of ontologies for large-scale data analysis in biomedicine and their use for translational research. Georgios V. Gkoutos's expertise lies in molecular informatics and bioinformatics. He has developed a number of biomedical ontologies and his research focuses on the association of genotype to phenotype, translational research and the discovery of novel disease genes and drugs. Corresponding author. Georgios V. Gkoutos,
doi:10.1093/bfgp/elr031 pmid:21987712 pmcid:PMC3189694 fatcat:xgppdrqndvba5ppmijvqhkuraa