Learning massive interpretable gene regulatory networks of the human brain by merging Bayesian networks

PLoS Comput Biol. 2023 Dec 1;19(12):e1011443. doi: 10.1371/journal.pcbi.1011443. eCollection 2023 Dec.

Abstract

We present the Fast Greedy Equivalence Search (FGES)-Merge, a new method for learning the structure of gene regulatory networks via merging locally learned Bayesian networks, based on the fast greedy equivalent search algorithm. The method is competitive with the state of the art in terms of the Matthews correlation coefficient, which takes into account both precision and recall, while also improving upon it in terms of speed, scaling up to tens of thousands of variables and being able to use empirical knowledge about the topological structure of gene regulatory networks. To showcase the ability of our method to scale to massive networks, we apply it to learning the gene regulatory network for the full human genome using data from samples of different brain structures (from the Allen Human Brain Atlas). Furthermore, this Bayesian network model should predict interactions between genes in a way that is clear to experts, following the current trends in explainable artificial intelligence. To achieve this, we also present a new open-access visualization tool that facilitates the exploration of massive networks and can aid in finding nodes of interest for experimental tests.

MeSH terms

  • Algorithms
  • Artificial Intelligence*
  • Bayes Theorem
  • Brain
  • Computational Biology / methods
  • Gene Regulatory Networks* / genetics
  • Humans

Grants and funding

This project has received funding from the European Union’s Horizon 2020 Framework Programme for Research and Innovation under Specific Grant Agreement No. 785907 to PL (HBP SGA2), and Specific Grant Agreement No. 945539 to CB (HBP SGA 3). The project has also received funding through the Spanish Ministry of Science and Innovation through the projects PID2022-139977NB-I00 to CB and TED2021-131310B-I00 "Bayesian Networks for Interpretable Machine Learning and Optimization" (BAYES-INTERPRET) to PL. The founders did not play any role on study design, data collection, analysis, decision to publish or preparation of the manuscript.