Inference of essential genes in Brugia malayi and Onchocerca volvulus by machine learning and the implications for discovering new interventions

Abstract

Detailed explorations of the model organisms Caenorhabditis elegans (elegant worm) and Drosophila melanogaster (vinegar fly) have substantially improved our knowledge and understanding of biological processes and pathways in metazoan organisms. Extensive functional genomic and multi-omic data sets have enabled the discovery and characterisation of ‘essential’ genes that are critical for the survival of these organisms. Recently, we showed that a machine learning (ML)-based pipeline could be utilised to predict essential genes in both C. elegans and D. melanogaster using features from DNA, RNA, protein and/or cellular data or associated information. As these distantly-related species are within the Ecdysozoa, we hypothesised that this approach could be suited for non-model organisms within the same group (phylum) of protostome animals. In the present investigation, we cross-predicted essential genes within the phylum Nematoda – between C. elegans and the parasitic filarial nematodes Brugia malayi and Onchocerca volvulus, and then ranked and prioritised these genes. Highly ranked genes were linked to key biological pathways or processes, such as ribosome biogenesis, translation and RNA processing, and were expressed at relatively high levels in the germline, gonad, hypodermis and/or nerves. The present in silico workflow is hoped to expedite the identification of drug targets in parasitic organisms for subsequent experimental validation in the laboratory.

Keywords

• Essential genes
• Machine learning
• Brugia malayi
• Onchocerca volvulus
• Filarioid
• Nematodes