Mapping between genotype and phenotype is often non-obvious, complicating prediction of genes underlying specific phenotypes. This problem can be addressed through comparative analyses of phenotypes. We define orthologous phenotypes between organisms (phenologs) based upon overlapping sets of orthologous genes associated with each phenotype. Comparisons of >189,000 human, mouse, yeast, and worm gene-phenotype associations reveal many significant phenologs, including novel non-obvious human disease models. For example, phenologs suggest a yeast model for mammalian angiogenesis defects and an invertebrate model for vertebrate neural tube birth defects. Phenologs thus create a rich framework for comparing mutational phenotypes, identify adaptive reuse of gene systems, and suggest new disease genes.
To search for phenologs, please go to the basic search page and enter your list of genes in the box provided, using Entrez gene identifiers for mouse/human genes, locus ids for yeast (e.g., YHR200W), or sequence names for worm (e.g., B0205.3). It is expected that this list of genes will all be associated with a particular system, trait, mutational phenotype, or disease. The search will return all identified model organism/human mutational phenotypes that show any overlap with the input set of the genes, ranked according to their hypergeometric probability scores. Clicking on a particular phenolog will result in a list of genes associated with the phenotype, from which potential new candidate genes can identified.
Currently known phenotypes in the database are available from the link labeled 'Find phenotypes', where the associated gene can be submitted as queries, or alternately, can be searched directly from the link below.
Systematic discovery of non-obvious human disease models through orthologous phenotypes
Kriston L. McGary, Tae Joo Park, John O. Woods, Hye Ji Cha, John B. Wallingford, and Edward M. Marcotte, Proc Natl Acad Sci U S A, in press (2010)
Search for phenologs
Search for phenotypes by keyword
Search for phenotypes associated with a gene and its orthologs
Precalculated phenologs from paper
An extension of the algorithm was published in:
Prediction of gene-phenotype associations in humans, mice, and plants using phenologs
John O. Woods, U. Martin Singh-Blom, Jon M. Laurent, Kriston L. McGary, Edward M. Marcotte. BMC Bioinformatics, in press (2013).
The supporting web site for this paper can be found here.
Questions/Comments: Email: marcotte AT icmb DOT utexas DOT edu