GENECI: A novel evolutionary machine learning consensus-based approach for the inference of gene regulatory networks

Abstract

Gene regulatory networks define the interactions between DNA products and other substances in cells. Increasing knowledge of these networks improves the level of detail with which the processes that trigger different diseases are described and fosters the development of new therapeutic targets. These networks are usually represented by graphs, and the primary sources for their correct construction are usually time series from differential expression data. The inference of networks from this data type has been approached differently in the literature. Mostly, computational learning techniques have been implemented, which have finally shown some specialization in specific datasets. For this reason, the need arises to create new and more robust strategies for reaching a consensus based on previous results to gain a particular capacity for generalization. This paper presents GENECI (GEne NEtwork Consensus Inference), an evolutionary machine learning approach that acts as an organizer for constructing ensembles to process the results of the main inference techniques reported in the literature and to optimize the consensus network derived from them, according to their confidence levels and topological characteristics. After its design, the proposal was confronted with datasets collected from academic benchmarks (DREAM challenges and IRMA network) to quantify its accuracy. Subsequently, it was applied to a real-world biological network of melanoma patients whose results could be contrasted with medical research collected in the literature. Finally, it has been proved that its ability to optimize the consensus of several networks leads to outstanding robustness and accuracy, gaining a certain generalization capacity after facing the inference of multiple datasets. The source code is hosted in a public repository at GitHub under MIT license: https://github.com/AdrianSeguraOrtiz/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/.

Keywords: Differential expression; Evolutionary algorithms; Gene regulatory networks; Machine learning.