Gene discovery informatics toolkit defines candidate genes for unexplained infertility and prenatal or infantile mortality

Gene Discovery Informatics Toolkit. a Data sources integrated within the Gene Discovery Informatics Toolkit. b Proportion of protein-coding genes found to be essential in yeast, human cells, mice and humans. Relative proportions of cell-essential genes are presented relative to the number of genes for which knockouts have been created (see Methods for details). Human-lethal genes were extracted through mining of OMIM database as described in methods, and proportion is shown relative to all protein-coding genes. c Venn diagram showing overlap between mouse lethal genes extracted from MGI13 and IMPC.15 (i) Overlap of genes annotated as inducing a pre-weaning lethal phenotype with recessive knockout in MGI and IMPC. (ii) 1290 genes with phenotypic information available for homozygous KO in both MGI and IMPC, with 84% concurrence in genes similarly annotated as inducing pre-weaning lethality by both sources. d Venn diagram showing overlap between cell ‘essentialomes’ described in the ref. 16–18 Analyses include only genes tested in all three studies (15,903/19,169 protein coding genes, see Methods). e Number of genes classified as cell-essential among eleven cell lines.16–18 Our criteria for an aggregated ‘cell essentialome’ was defined as all genes shown to be essential for cellular viability in three or more cell lines, among any of the three studies. f Venn diagrams showing overlap between OMIM genes and mouse lethal and cell essential genes. (ii) Overlap of murine and cell essentialomes among all protein coding genes (16,764 genes which have either cell or mouse data, including 3118 OMIM genes shown in the grey Venn circle). (ii) Dataset is restricted to include only 8536 genes with both mouse and cell phenotypic information available. Note that areas of circles in Fii are not exactly correlated to numbers of genes but are largely representative of proportion