Figure 2

The matrix formalism for calculating phenolog overlaps is especially important when predicting between species where large gene family expansions have occurred since species divergence, such as between Arabidopsis and humans. The example uses human and mouse to illustrate the orthogroup-based matrix formalism. (a) Phenotype associations (colors) are plotted as graphs for genes from human (left nodes, subscripted h) and mouse (right nodes, subscripted m), showing genes’ orthology relationships (edges radiating from orthogroups — middle nodes, labeled O). The orthologies (from INPARANOID), are used to “translate” phenotype associations between species (in the case of the gene-based matrix framework in panels (b, c)) or into an intermediate collection of orthogroup-phenotype associations (for the orthogroup-based matrix framework in (d)). Orthogroup vertices (e.g., O _A ) connect human and mouse orthologs (such as A _h , A h′, and A h″, which are paralogs of one another relative to the human-mouse divergence, with A _m and A m′. Red vertices within a species are genes associated with the phenotype of interest (ϕ _h for human and ϕ _m for the mouse phenotype); orthogroup colors reflect the species data. These associations can alternately be captured by representing the graphs as matrices (b-d), with bullets indicating an assocation between a given genetic element and a phenotype. Specifically, (b) and (c) represent the gene-based formalism, and (d) illustrates the orthogroup-based formalism. Human and mouse phenotype columns are indicated by ϕ _h and ϕ _m , respectively.