Multi-objective context-guided consensus of a massive array of techniques for the inference of Gene Regulatory Networks.

Publisher: Elsevier Country of Publication: United States NLM ID: 1250250 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0534 (Electronic) Linking ISSN: 00104825 NLM ISO Abbreviation: Comput Biol Med Subsets: MEDLINE

Publication: New York : Elsevier
Original Publication: New York, Pergamon Press.

Gene Regulatory Networks* ; Algorithms*; Computational Biology/methods ; Humans ; Bayes Theorem ; Software

Background and Objective: Gene Regulatory Network (GRN) inference is a fundamental task in biology and medicine, as it enables a deeper understanding of the intricate mechanisms of gene expression present in organisms. This bioinformatics problem has been addressed in the literature through multiple computational approaches. Techniques developed for inferring from expression data have employed Bayesian networks, ordinary differential equations (ODEs), machine learning, information theory measures and neural networks, among others. The diversity of implementations and their respective customization have led to the emergence of many tools and multiple specialized domains derived from them, understood as subsets of networks with specific characteristics that are challenging to detect a priori. This specialization has introduced significant uncertainty when choosing the most appropriate technique for a particular dataset. This proposal, named MO-GENECI, builds upon the basic idea of the previous proposal GENECI and optimizes consensus among different inference techniques, through a carefully refined multi-objective evolutionary algorithm guided by various objective functions, linked to the biological context at hand.
Methods: MO-GENECI has been tested on an extensive and diverse academic benchmark of 106 gene regulatory networks from multiple sources and sizes. The evaluation of MO-GENECI compared its performance to individual techniques using key metrics (AUROC and AUPR) for gene regulatory network inference. Friedman's statistical ranking provided an ordered classification, followed by non-parametric Holm tests to determine statistical significance.
Results: MO-GENECI's Pareto front approximation facilitates easy selection of an appropriate solution based on generic input data characteristics. The best solution consistently emerged as the winner in all statistical tests, and in many cases, the median precision solution showed no statistically significant difference compared to the winner.
Conclusions: MO-GENECI has not only demonstrated achieving more accurate results than individual techniques, but has also overcome the uncertainty associated with the initial choice due to its flexibility and adaptability. It is shown intelligently to select the most suitable techniques for each case. The source code is hosted in a public repository at GitHub under MIT license: https://github.com/AdrianSeguraOrtiz/MO-GENECI. Moreover, to facilitate its installation and use, the software associated with this implementation has been encapsulated in a Python package available at PyPI: https://pypi.org/project/geneci/.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Keywords: Consensus; Expression data; Gene regulatory network; Inference; Multi-objective evolutionary algorithm

Date Created: 20240716 Date Completed: 20240814 Latest Revision: 20240814

20240814

10.1016/j.compbiomed.2024.108850

39013340