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Article

eSIG-Net: an interaction language model that decodes the protein code of single mutations.

Nature methods - 1 Jun 2026

Pan Xingxin, Shrawat Aditya, Raghavan Sidharth, Dong Chuanpeng, Yang Yuntao, Li Zhao, Zheng W Jim, Eckhardt S Gail, Wu Erxi, Fuxman Bass Juan I, Jarosz Daniel F, Chen Sidi, McGrail Daniel J, Sheynkman Gloria M, Huang Jason H, Sahni Nidhi, Yi S Stephen

Abstract excerpt

Most proteins act through interactions with other molecules, yet predicting how single mutations perturb these interactions-defined as 'protein codes'-remains a central challenge in computational biology. Here we introduce eSIG-Net, the edgetic mutation sequence-based interaction grammar network, a language model that integrates protein sequence embeddings with syntax-aware and evolution-aware mutation encoding...

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PMID: 42056223
DOI: 10.1038/s41592-026-03086-x
PMCID: PMC13259923

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