Uncovering the Genomic Manifold via Scalable Learning from the Global Microbiome
Weimin WuiD, Zhihan ZhouiD, Robert W. RileyiD, Mohammad AbdulqaderiD, Xuefeng SongiD, Satria Ardhe KautsariD, Rob S EganiD, Steven A. HofmeyriD, Gefei LiuiD, Shira Goldhaber-GordoniD, Mutian YuiD, Harrison HoiD, Yaping LiuiD, Andrei Stecca SteindorffiD, Fengchen LiuiD, Feng CheniD, Rachael M. Morgan‐KissiD, Lizhen ShiiD, Han LiuiD, Zhong WangiD
Abstract
Functional genomic sequences occupy an infinitesimal fraction of the astronomically large DNA sequence space, implying that evolution explores a low-dimensional manifold shaped by universal biochemical and evolutionary constraints. To investigate this underexplored Genomic Manifold Hypothesis using scalable, data-driven evidence, we developed GenomeOcean, a 4-billion-parameter generative model trained on 219 TB of diverse, co-assembled global environmental metagenomic data using an optimized transformer. The model captures both universal phylogenetic syntax and protein-coding fidelity. Furthermore, we validate the embeddings intrinsic low dimensionality. Crucially, comparisons with the independently trained Evo 2 model demonstrate a strong linear correspondence between their embedding spaces and convergent generative behaviors. These results suggest that the genomic manifold represents a fundamental biological principle, offering a unified framework for understanding evolutionary constraints and guiding synthetic biology.
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