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Abstract MotivationBranch lengths and topology of a species tree are essential in most downstream analyses, including estimation of diversification dates, characterization of selection, understanding adaptation, and comparative genomics. Modern phylogenomic analyses often use methods that account for the heterogeneity of evolutionary histories across the genome due to processes such as incomplete lineage sorting. However, these methods typically do not generate branch lengths in units that are usable by downstream applications, forcing phylogenomic analyses to resort to alternative shortcuts such as estimating branch lengths by concatenating gene alignments into a supermatrix. Yet, concatenation and other available approaches for estimating branch lengths fail to address heterogeneity across the genome. ResultsIn this article, we derive expected values of gene tree branch lengths in substitution units under an extension of the multispecies coalescent (MSC) model that allows substitutions with varying rates across the species tree. We present CASTLES, a new technique for estimating branch lengths on the species tree from estimated gene trees that uses these expected values, and our study shows that CASTLES improves on the most accurate prior methods with respect to both speed and accuracy. Availability and implementationCASTLES is available at https://github.com/ytabatabaee/CASTLES. 

This book constitutes the refereed proceedings of the 27th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2023, held in Istanbul, Turkey, from April 16–19, 2023. The 11 regular and 33 short papers presented in this book were carefully reviewed and selected from 188 submissions. The papers report on original research in all areas of computational molecular biology and bioinformatics.