Case study of regulation of exit from mitosis in D. rerio
This example workflow illustrates how functional knowledge transfer allows IMP to predict processes that are not well studied in an organism.
Search for regulation of exit from mitosis
The biological process regulation of exit from mitosis (GO:0007096) represents a crucial mitotic cell cycle process that enable cells to regulate the exit from M phase. This process in zebrafish had no experimental annotations at the time when data were gathered for IMPv1.0, however the process has been extensively studied in yeast, mouse and fly.
IMP for unannotated processes
The functional knowledge transfer method allows IMP to identify functional analogs (from 11 yeast, 1 rat, 1 mouse, and 5 fly genes) in zebrafish enabling novel gene membership predictions to this process.
Gene predictions for regulation of exit from mitosis
IMP predicts that cdh2 (neuronal cadherin 2) is also a member of this process based on its connectedness to the functional analogs of genes annotated to this process in other species. Not only is cdh2 not in our gold standard or input data, but also none of cdh2's homologs have been annotated to the regulation of exit from mitosis.
Experimental validation of cdh2's role
A recent study, the results of which were not included in IMPv1.0, has implicated cdh2 in the process regulation of exit from mitosis. Yamaguchi et al. [1] found that cdh2 mutants have disrupted retinal epithelium. Their detailed experimental assays found that, in these cells, cdh2 mutants changed the proportion of cells underging neurogenic cell division. Cadherins are important transmembrane proteins that play crucial role in cell adhesion in multi-cellular organisms. Thus, the gap in our knowledge can in part be attributed to the lack of a cdh2 ortholog in the single cell model organism yeast where cell-cycle checkpoints have been extensively studied.
References
1. Yamaguchi M, Imai F, Tonou-Fujimori N, Masai I. (2010) Mutations in N-cadherin and a Stardust homolog, Nagie oko, affect cell-cycle exit in zebrafish retina. Mech. Dev., 127(5-6), 247–264.