Defining characteristics and conservation of poorly annotated genes in Caenorhabditis elegans using WormCat 2.0

Genetics. 2022 May 19;iyac085. doi: 10.1093/genetics/iyac085. Online ahead of print.


Omics tools provide broad data sets for biological discovery. However, the computational tools for identifying important genes or pathways in RNA seq, proteomics or GWAS data depend on GO annotations and are biased toward well-described pathways. This limits their utility as poorly annotated genes, which could have novel functions, are often passed over. Recently, we developed an annotation and category enrichment tool for Caenorhabditis elegans genomic data, WormCat, that provides an intuitive visualization output. Unlike GO-based enrichment tools, which exclude genes with no annotation information, WormCat 2.0 retains these genes as a special UNASSIGNED category. Here, we show that the UNASSIGNED gene category enrichment exhibits tissue-specific expression patterns and can include genes with biological functions identified in published datasets. Poorly annotated genes are often considered to be potentially species-specific and thus, of reduced interest to the biomedical community. Instead, we find that around 3% of the UNASSIGNED genes have human orthologs, including some linked to human diseases. These human orthologs themselves have little annotation information. A recently developed method that incorporates lineage relationships (abSENSE) indicates that failure of BLAST to detect homology explains the apparent lineage specificity for many UNASSIGNED genes. This suggests that a larger subset could be related to human genes. WormCat provides an annotation strategy that allows association of UNASSIGNED genes with specific phenotypes and known pathways. Building these associations in C. elegans, with its robust genetic tools, provides a path to further functional study and insight into these understudied genes.

Keywords: C. elegans; Function of unknown genes; Gene Enrichment.