德国弗里德里希席勒大学耶拿Sebastian Böcker和Kai Dührkop研究小组在研究中取得进展。他们的论文扩充了谱库中缺失代谢物的高可信度结构注释。这一研究成果发表在2021年10月14日出版的国际学术期刊《自然-生物技术》上。

在本研究中，研究人员介绍了COSMIC工作流程，该工作流程将计算机结构数据库生成和注释和内核密度P值估计与具有强制特征方向性的支持向量机组成的置信度分数相结合。在不同的数据集上，COSMIC可在低错误率水平匹配大量注释，并且优于谱库搜索。

为了证明COSMIC可以注释以前从未报道过的结构，研究人员注释了12种天然胆汁酸。九个结构的注释通过人工评估确认，两个结构使用合成标准确认。在人类样本中，研究人员注释并手动验证了人类代谢组数据库中目前未知的315种分子结构。将COSMIC应用于由17,400次代谢组学实验得到的数据，产生了1,715个高可信度结构注释，而这些注释是光谱库中不存在的。

据悉，非靶向代谢组学实验依赖光谱库进行结构注释，但通常只有一小部分光谱可用于匹配。已有的计算机方法可在结构数据库中搜索，但无法区分正确和不正确的注释。

附：英文原文

Title: High-confidence structural annotation of metabolites absent from spectral libraries

Author: Hoffmann, Martin A., Nothias, Louis-Flix, Ludwig, Marcus, Fleischauer, Markus, Gentry, Emily C., Witting, Michael, Dorrestein, Pieter C., Dhrkop, Kai, Bcker, Sebastian

Issue&Volume: 2021-10-14

Abstract: Untargeted metabolomics experiments rely on spectral libraries for structure annotation, but, typically, only a small fraction of spectra can be matched. Previous in silico methods search in structure databases but cannot distinguish between correct and incorrect annotations. Here we introduce the COSMIC workflow that combines in silico structure database generation and annotation with a confidence score consisting of kernel density P value estimation and a support vector machine with enforced directionality of features. On diverse datasets, COSMIC annotates a substantial number of hits at low false discovery rates and outperforms spectral library search. To demonstrate that COSMIC can annotate structures never reported before, we annotated 12 natural bile acids. The annotation of nine structures was confirmed by manual evaluation and two structures using synthetic standards. In human samples, we annotated and manually validated 315 molecular structures currently absent from the Human Metabolome Database. Application of COSMIC to data from 17,400 metabolomics experiments led to 1,715 high-confidence structural annotations that were absent from spectral libraries. 

DOI: 10.1038/s41587-021-01045-9

Source: https://www.nature.com/articles/s41587-021-01045-9