ArticleBMC genomics2010
Drug target prediction and prioritization: using orthology to predict essentiality in parasite genomes.
Article in BMC genomics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 84 citations in OpenAlex.
- Informatic challenges and advances in illuminating the druggable proteome.Drug discovery today · 2024Review
- 'Bingo'-a large language model- and graph neural network-based workflow for the prediction of essential genes from protein data.Briefings in bioinformatics · 2023Article
- Targeting Metalloenzymes: The "Achilles' Heel" of Viruses and Parasites.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Recent trends in next generation immunoinformatics harnessed for universal coronavirus vaccine design.Pathogens and global health · 2023Review
- In silico Methods for Identification of Potential Therapeutic Targets.Interdisciplinary sciences, computational life sciences · 2022Review
- Identification of essential genes in Caenorhabditis elegans through whole-genome sequencing of legacy mutant collections.G3 (Bethesda, Md.) · 2021Article
- Cross-Predicting Essential Genes between Two Model Eukaryotic Species Using Machine Learning.International journal of molecular sciences · 2021Article
- Phylum-Spanning Neuropeptide GPCR Identification and Prioritization: Shaping Drug Target Discovery Pipelines for Nematode Parasite Control.Frontiers in endocrinology · 2021Article
- Prioritization of potential drug targets and antigenic vaccine candidates againstJournal of proteins and proteomics · 2021Article
- Evolution of Protein-Mediated Biomineralization in Scleractinian Corals.Frontiers in genetics · 2021Article
- Combined use of feature engineering and machine-learning to predict essential genes inNAR genomics and bioinformatics · 2020Article
- Article
- Predicting gene essentiality inComputational and structural biotechnology journal · 2020Article
- An Evaluation of Machine Learning Approaches for the Prediction of Essential Genes in Eukaryotes Using Protein Sequence-Derived Features.Computational and structural biotechnology journal · 2019Article
- Interactive online application for the prediction, ranking and prioritisation of drug targets in Schistosoma haematobium.Parasites & vectors · 2018Article
- Accurate prediction of orthologs in the presence of divergence after duplication.Bioinformatics (Oxford, England) · 2018Article
- Crystal structures and inhibition of Trypanosoma brucei hypoxanthine-guanine phosphoribosyltransferase.Scientific reports · 2016Article
- Article
- Novel Drug Targets for Food-Borne Pathogen Campylobacter jejuni: An Integrated Subtractive Genomics and Comparative Metabolic Pathway Study.Omics : a journal of integrative biology · 2015Article
- Genetic blueprint of the zoonotic pathogen Toxocara canis.Nature communications · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNew drug targets are urgently needed for parasites of socio-economic importance. Genes that are essential for parasite survival are highly desirable targets, but information on these genes is lacking, as gene knockouts or knockdowns are difficult to perform in many species of parasites. We examined the applicability of large-scale essentiality information from four model eukaryotes, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Saccharomyces cerevisiae, to discover essential genes in each of their genomes. Parasite genes that lack orthologues in their host are desirable as selective targets, so we also examined prediction of essential genes within this subset.
resultsCross-species analyses showed that the evolutionary conservation of genes and the presence of essential orthologues are each strong predictors of essentiality in eukaryotes. Absence of paralogues was also found to be a general predictor of increased relative essentiality. By combining several orthology and essentiality criteria one can select gene sets with up to a five-fold enrichment in essential genes compared with a random selection. We show how quantitative application of such criteria can be used to predict a ranked list of potential drug targets from Ancylostoma caninum and Haemonchus contortus--two blood-feeding strongylid nematodes, for which there are presently limited sequence data but no functional genomic tools.
conclusionsThe present study demonstrates the utility of using orthology information from multiple, diverse eukaryotes to predict essential genes. The data also emphasize the challenge of identifying essential genes among those in a parasite that are absent from its host.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.