近日，美国哈佛大学Curtis Huttenhower及其小组发现了预测微生物群落中未表征基因产物的功能。2025年10月15日出版的《自然—生物技术》发表了这项成果。

在这里，小组开发了一种方法，通过评估社区范围内的多组学数据来推断微生物蛋白质的推测功能。该研究团队预测了44.3万个蛋白质家族（约82.3%以前未被表征）的高置信度函数，其中包括2.7万个与已知蛋白质具有弱同源性的蛋白质家族和6000个没有同源性的蛋白质家族。这些数据来自人类微生物组综合计划（HMP2/iHMP）的1595个肠道宏基因组和800个亚转录组。整合诸如序列相似性、基因组接近性和域域相互作用等附加信息可以提高方法的性能。

他们的方法FUGAsseM是可推广的，并预测蛋白质功能在充分研究和未充分表征的社区。与最先进的应用于单一生物的方法相比，FUGAsseM在微生物群落的背景下达到了相似的精度水平，同时提供了更大的覆盖范围。这项初步研究扩展了人类肠道微生物组的功能景观，并允许在特征不充分的群落中探索微生物蛋白。

据了解，微生物群落中的大多数基因仍未被确定。

附：英文原文

Title: Predicting functions of uncharacterized gene products from microbial communities

Author: Zhang, Yancong, Bhosle, Amrisha, Bae, Sena, Eckenrode, Kelly, Huang, Xueying, Tang, Jingjing, Lavrentovich, Danylo, Awad, Lana, Hua, Ji, Wang, Ya, Morgan, Xochitl C., Li, Bin, Krueger, Andy, Garrett, Wendy S., Franzosa, Eric A., Huttenhower, Curtis

Issue&Volume: 2025-10-15

Abstract: The majority of genes in microbial communities remain uncharacterized. Here we develop a method to infer putative function for microbial proteins at scale by assessing community-wide multiomics data. We predict high-confidence functions for >443,000 protein families (~82.3% previously uncharacterized), including >27,000 protein families with weak homology to known proteins and >6,000 protein families without homology. These were drawn from 1,595 gut metagenomes and 800 metatranscriptomes from the Integrative Human Microbiome Project (HMP2/iHMP). Integrating additional information such as sequence similarity, genomic proximity and domain–domain interactions improves performance of the method. Our method’s implementation, FUGAsseM, is generalizable and predicts protein function in both well-studied and undercharacterized communities. FUGAsseM achieves similar levels of accuracy in the context of microbial communities when compared to state-of-the-art approaches designed for application to single organisms while simultaneously providing much greater breadth of coverage. This initial study expands the functional landscape of the human gut microbiome and allows for exploration of microbial proteins in undercharacterized communities.

DOI: 10.1038/s41587-025-02813-7

Source: https://www.nature.com/articles/s41587-025-02813-7