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bioRxiv · 10.1101/2024.12.19.629561

Multiomic foundation model predicts epigenetic regulation by zero-shot

Yang, Z.·Fan, X.·Lan, M.·Li, X.·You, Y.·Tian, L.·Church, G.·Liu, X.·Gu, F.
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Abstract

Deciphering cell type-specific perturbation effects on genes and cellular states demands considerable experimental resources. To overcome this challenge, we propose Perturbation Transformer (PertFormer), a foundation model to uncover functional and regulatory mechanisms through interpretable in silico perturbation process. PertFormer comprises 3 billion parameters pretrained on both bulk and single-cell datasets covering 9 types of multiomics (55 billion bp bulk multiomics and the largest-to-date 1.5 billion paired multiomic samples from 1 million single cells), capturing regulation of 300 kb around every genic region. PertFormer enables zero-shot prediction of functional perturbations and cell fate dynamics, outperforming existing methods by 20.9%-480.2%. PertFormer identifies novel tumor treatment targets, validated experimentally. The generalization capabilities of PertFormer have the potential to accelerate the discovery of biological and clinical targets.

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Yang, Z., Fan, X., Lan, M., Li, X., You, Y., Tian, L., Church, G., Liu, X., Gu, F.. 2024-12-22. Multiomic foundation model predicts epigenetic regulation by zero-shot. https://doi.org/10.1101/2024.12.19.629561

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