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A Phylogenetic Approach to Genomic Language Modeling

Published: March 4, 2025 | arXiv ID: 2503.03773v1

By: Carlos Albors , Jianan Canal Li , Gonzalo Benegas and more

BigTech Affiliations: University of California, Berkeley

Potential Business Impact:

Finds important parts of our DNA.

Business Areas:
Bioinformatics Biotechnology, Data and Analytics, Science and Engineering

Genomic language models (gLMs) have shown mostly modest success in identifying evolutionarily constrained elements in mammalian genomes. To address this issue, we introduce a novel framework for training gLMs that explicitly models nucleotide evolution on phylogenetic trees using multispecies whole-genome alignments. Our approach integrates an alignment into the loss function during training but does not require it for making predictions, thereby enhancing the model's applicability. We applied this framework to train PhyloGPN, a model that excels at predicting functionally disruptive variants from a single sequence alone and demonstrates strong transfer learning capabilities.

Country of Origin
🇺🇸 United States

Page Count
15 pages

Category
Quantitative Biology:
Genomics