CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Biotechnol. 2022 Jun;40(6):921-931. doi: 10.1038/s41587-022-01226-0. Epub 2022 Mar 3.
The human gut microbiome encodes a large variety of antimicrobial peptides (AMPs), but the short lengths of AMPs pose a challenge for computational prediction. Here we combined multiple natural language processing neural network models, including LSTM, Attention and BERT, to form a unified pipeline for candidate AMP identification from human gut microbiome data. Of 2,349 sequences identified as candidate AMPs, 216 were chemically synthesized, with 181 showing antimicrobial activity (a positive rate of >83%). Most of these peptides have less than 40% sequence homology to AMPs in the training set. Further characterization of the 11 most potent AMPs showed high efficacy against antibiotic-resistant, Gram-negative pathogens and demonstrated significant efficacy in lowering bacterial load by more than tenfold against a mouse model of bacterial lung infection. Our study showcases the potential of machine learning approaches for mining functional peptides from metagenome data and accelerating the discovery of promising AMP candidate molecules for in-depth investigations.
人类肠道微生物组编码了大量的抗菌肽 (AMPs),但 AMP 的短长度给计算预测带来了挑战。在这里,我们结合了多种自然语言处理神经网络模型,包括 LSTM、Attention 和 BERT,形成了一个从人类肠道微生物组数据中识别候选 AMP 的统一管道。在确定的 2349 个候选 AMP 序列中,有 216 个经过化学合成,其中 181 个具有抗菌活性(阳性率>83%)。这些肽的大多数与训练集中的 AMP 序列的同源性小于 40%。对 11 种最有效的 AMP 的进一步表征表明,它们对耐抗生素的革兰氏阴性病原体具有很高的疗效,并在细菌肺部感染的小鼠模型中显示出了将细菌载量降低十倍以上的显著疗效。我们的研究展示了机器学习方法从宏基因组数据中挖掘功能肽的潜力,并加速了有前途的 AMP 候选分子的发现,以进行深入研究。
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