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Signal Peptides Generated by Attention-Based Neural Networks
Author(s) -
Zachary Wu,
Kevin Yang,
Michael J. Liszka,
Alycia Lee,
Alina Batzilla,
David G. Wernick,
David P. Weiner,
Frances H. Arnold
Publication year - 2020
Publication title -
acs synthetic biology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.156
H-Index - 66
ISSN - 2161-5063
DOI - 10.1021/acssynbio.0c00219
Subject(s) - signal peptide , bacillus subtilis , amino acid , computational biology , artificial neural network , peptide , biochemistry , peptide sequence , protein sequencing , secretion , biology , chemistry , computer science , artificial intelligence , genetics , gene , bacteria
Short (15-30 residue) chains of amino acids at the amino termini of expressed proteins known as signal peptides (SPs) specify secretion in living cells. We trained an attention-based neural network, the Transformer model, on data from all available organisms in Swiss-Prot to generate SP sequences. Experimental testing demonstrates that the model-generated SPs are functional: when appended to enzymes expressed in an industrial Bacillus subtilis strain, the SPs lead to secreted activity that is competitive with industrially used SPs. Additionally, the model-generated SPs are diverse in sequence, sharing as little as 58% sequence identity to the closest known native signal peptide and 73% ± 9% on average.

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