Abstract
Phylogenetic inference is fundamental to modern biology, with applications spanning evolutionary biology, epidemiology, and comparative genomics. While maximum likelihood and Bayesian methods remain the gold standard due to their statistical rigor, they rely on simplifying evolutionary assumptions and are computationally intensive. Existing machine learning approaches offer speed advantages, but face several limitations: exclusive reliance on simulated training data, inadequate handling of gaps, focus primarily on topology rather than complete tree reconstruction, and sensitivity to input sequence order. Here, we introduce IQ-NET (Intelligent Quartet NETwork), a machine learning framework that addresses these limitations through training exclusively on real datasets, simultaneous inference of topology and branch lengths from gapped alignments without substitution model assumptions, and robustness to the order of input sequences. IQ-NET outperforms existing machine learning methods and achieves both higher accuracy and a 24-fold speedup over the IQ-TREE software. We also demonstrate IQ-NET's utility in species tree reconstruction by integrating it with ASTRAL.
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Phylogenetic inference is fundamental to modern biology, with many applications including evolutionary biology, epidemiology, and comparative genomics. While maximum likelihood and Bayesian methods remain the gold standard for phylogenetic analysis, they rely on simplifying assumptions and are computationally intensive. Recent machine learning approaches for phylogenetics offer speed advantages, but have several limitations: exclusive reliance on simulated data for training, inadequate handling of gaps, and sensitivity to input sequence order. Here, we introduce IQ-NET (Intelligent Quartet NETwork), a deep learning framework that solves these limitations to infer four-taxon trees. IQ-NET estimates both tree topology and branch lengths directly from gapped alignments. IQ-NET outperforms existing machine learning methods in terms of accuracy, and obtained a 24-fold speedup compared with the widely used maximum likelihood software, IQ-TREE. We finally introduce a pipeline using IQ-NET and the ASTRAL software to reconstruct a larger species tree, i.e., with more than four taxa.
https://doi.org/10.32942/X2ND3S
Artificial Intelligence and Robotics
Phylogenetic inference, machine learning, Quartet analysis, Empirical data training
Published: 2025-11-25 23:50
Last Updated: 2026-05-05 14:42
CC BY Attribution 4.0 International
Language:
English
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