HELP: A computational framework for labelling and predicting human common and context-specific essential genes

PLoS Comput Biol. 2024 Sep 27;20(9):e1012076. doi: 10.1371/journal.pcbi.1012076. eCollection 2024 Sep.

Abstract

Machine learning-based approaches are particularly suitable for identifying essential genes as they allow the generation of predictive models trained on features from multi-source data. Gene essentiality is neither binary nor static but determined by the context. The databases for essential gene annotation do not permit the personalisation of the context, and their update can be slower than the publication of new experimental data. We propose HELP (Human Gene Essentiality Labelling & Prediction), a computational framework for labelling and predicting essential genes. Its double scope allows for identifying genes based on dependency or not on experimental data. The effectiveness of the labelling method was demonstrated by comparing it with other approaches in overlapping the reference sets of essential gene annotations, where HELP demonstrated the best compromise between false and true positive rates. The gene attributes, including multi-omics and network embedding features, lead to high-performance prediction of essential genes while confirming the existence of essentiality nuances.

MeSH terms

  • Algorithms
  • Computational Biology* / methods
  • Databases, Genetic
  • Genes, Essential* / genetics
  • Humans
  • Machine Learning*
  • Molecular Sequence Annotation / methods
  • Software

Grants and funding

I.G. acknowledges support from the POR-Lazio FESR 2014-2020 - project H35F21000430002 (https://www.lazioeuropa.it/). The work of I.G. and M.G. was partially funded by European Union - Next Generation EU, M4C2 PRIN 2022 project "ABCare: The Asplenia Biobanking Community: from Analytes to theRapEutic decision making" Prot. 2022Y59MHL – DD n. 104 02-02-2022 CUP B53D23020860006. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.