AUTHOR=Raymond Mélanie , Descary Marie-Hélène , Beaulac Cédric , Larribe Fabrice 

TITLE=Constructing ancestral recombination graphs through reinforcement learning

JOURNAL=Frontiers in Genetics

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2025.1569358

DOI=10.3389/fgene.2025.1569358

ISSN=1664-8021

ABSTRACT=IntroductionOver the years, many approaches have been proposed to build ancestral recombination graphs (ARGs), graphs used to represent the genetic relationship between individuals. Among these methods, many rely on the assumption that the most likely graph is among those with the fewest recombination events. In this paper, we propose a new approach to build maximum parsimony ARGs: Reinforcement Learning (RL).MethodsWe exploit the similarities between finding the shortest path between a set of genetic sequences and their most recent common ancestor and finding the shortest path between the entrance and exit of a maze, a classic RL problem. In the maze problem, the learner, called the agent, must learn the directions to take in order to escape as quickly as possible, whereas in our problem, the agent must learn the actions to take between coalescence, mutation, and recombination in order to reach the most recent common ancestor as quickly as possible.ResultsOur results show that RL can be used to build ARGs with as few recombination events as those built with a heuristic algorithm optimized to build minimal ARGs, and sometimes even fewer. Moreover, our method allows to build a distribution of ARGs with few recombination events for a given sample, and can also generalize learning to new samples not used during the learning process.DiscussionRL is a promising and innovative approach to build ARGs. By learning to construct ARGs just from the data, our method differs from conventional methods that rely on heuristic rules or complex theoretical models.