Enrichment analysis

Enrichment analyses on the four axes (H, D, GD, and GH) were done using a hypergeometric test on the contributing genes. Enriched categories were filtered according to the following criteria: Bonferroni-corrected p < 0.05; size of the category, n > 3; and size of the overlap, n > 2.

We used the following databases: the WormBase [38] WS258 gene class names, anatomy terms, phenotypes, RNAi phenotypes, developmental stage expression, and disease-related genes [39]; the ModERN resource transcription-factor binding sites [40], which were mapped to transcription start sites (according to [41]). Additionally, we performed an enrichment analysis with DAVID 6.8 with the pre-defined selection of settings: Functional Categories (COG_Ontology, UP_keywords, Up_seq_feature), Gene_ontology (goterm_bp_direct, goterm_cc_direct, goterm_mf_direct), Pathways (KEGG_pathway), Protein_domains (Interpro, Pir_superfamiy, smart) [42, 43].