WormPaths: Caenorhabditis elegans metabolic pathway annotation and visualization

Abstract

In our group, we aim to understand metabolism in the nematode Caenorhabditis elegans and its relationships with gene expression, physiology and the response to therapeutic drugs. Visualization of the metabolic pathways that comprise the metabolic network is extremely useful for interpreting a wide variety of experiments. Detailed annotated metabolic pathway maps for C. elegans is mostly limited to pan-organismal maps, many with incomplete or inaccurate pathway and enzyme annotations. Here we present WormPaths, which is composed of two parts: 1) the careful manual annotation of metabolic genes into pathways, categories and levels, and 2) 62 pathway maps that include metabolites, metabolite structures, genes, reactions, and pathway connections between maps. These maps are available on the WormFlux website. We show that WormPaths provides easy-to-navigate maps and that the different levels in WormPaths can be used for metabolic pathway enrichment analysis of transcriptomic data. In the future we envision further developing these maps to be more interactive, with an analogy of road maps that are available on mobile devices.

A D-2-Hydroxyglutarate dehydrogenase mutant reveals a critical role for ketone body metabolism in Caenorhabditis elegans development

“…Overall, 315 and 183 genes are induced and repressed by loss of dhgd-1 , respectively ( Table S2 ). WormFlux (Yilmaz and Walhout, 2016) pathway enrichment analysis using pathways defined by WormPaths (Walker et al, 2021) revealed two main insights. First, the propionate shunt is not fully repressed by vitamin B12 in Δ dhgd-1 mutants ( Figures 4A, B, Table S3 ).…”

“…Correlation in expression between metabolic gene pairs across the compendium was calculated as Pearson Correlation Coefficient. Gene set enrichment analysis (GSEA) was performed on the ranked coexpression list using the PreRank module of GSEA (Subramanian et al, 2005) with pathway-to-gene annotations from WormPaths (Walker et al, 2021) and the significance cutoff set at a FDR of less than or equal to 0.05.…”

“…In C. elegans , these tissues function as both gut and liver, which are the primary sites of nutrient absorption, digestion, and metabolism 20,24 . The other propionate shunt genes exhibit less stringent tissue-specific expression and have been annotated to be involved in other metabolic pathways, including ketone body metabolism 19 . Since acdh-1 expression is required for propionate shunt flux 7 , this indicates that this pathway is not operational in body wall muscle early in development.…”

Bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism

“…These genes include dhs-19 , which encodes a short-chain d e h ydrogena s e of unknown function that localizes to lipid droplets 30 and is predicted to function in retinol metabolism 31 . The other two genes, elo-3 and elo-6, both encode elongases predicted to be involved in long chain FA biosynthesis 32, 33 . We generated a dhs-19 deletion mutant by CRISPR/Cas9 genome editing and confirmed that this strain is indeed more sensitive to tamoxifen ( Fig.…”

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

“…In addition, we included annotation lists specific for the commonly used RNAi libraries and found these could reveal enriched pathways in data from an RNAi screen. WormCat has been rapidly adopted by the C. elegans community (Albarqi and Ryder 2021 ; Lee et al 2021 ; Naim et al 2021 ; Tecle et al 2021 ; Zhang et al 2021 ) and adapted into a metabolism-focused tool ( Walker et al 2021 ) as well as an integrated gene expression analysis program ( Cheng et al 2021 ).…”