In silico fragmentation for computer assisted identification of metabolite mass spectra.
In silico fragmentation for computer assisted identification of metabolite mass spectra.
复制标题
DOI：
10.1186/1471-2105-11-148
复制
发表时间：
2010-03-22
影响因子：
3
通讯作者：
Neumann S
中科院分区：
文献类型：
--
作者：
Wolf S;Schmidt S;Müller-Hannemann M;Neumann S
质谱法已成为代谢组学研究中的首选分析方法。未知化合物的鉴定是主要的瓶颈。除了前体质量外，串联MS光谱还携带信息片段峰，但测量的参比化合物的光谱库的覆盖范围远远不能覆盖完整的化学空间。化合物库（如PubChem或KEGG）描述了大量化合物，可用于将其计算机碎片与未知代谢物的光谱进行比较。我们创建了MetFrag套件，以基于前体质量从化合物库中获得候选列表，随后通过测量片段和计算机片段之间的一致性进行排名。在评估中，MetFrag能够在KEGG中通过精确质量查询返回的前3个候选化合物中对大多数正确化合物进行排名。与先前发表的研究相比，MetFrag获得了比商业MassFrontier软件更好的结果。特别是对于大型化合物库，具有良好得分的候选物显示出高的结构相似性或只是不同的立体化学，随后基于化学距离的聚类减少了这种冗余。计算机碎片化处理一个分子需要不到一秒的时间，MetFrag在普通台式PC上分别在KEGG或PubChem中平均在30到300秒内进行搜索。我们提出了一种方法，能够识别小分子串联MS测量，即使没有光谱参考数据或一个大的碎片规则集。有了今天庞大的通用化合物库，我们获得了数十个非常相似的候选化合物，这仍然允许对正确的化合物类别进行自信的估计。我们的工具MetFrag改进了从串联MS光谱中识别未知物质的能力，并提供了比同类商业软件更好的结果。MetFrag可通过Web应用程序，Web服务和Java库获得。Web前端允许最终用户分析单个光谱并浏览结果，而Web服务和控制台应用程序旨在执行批量搜索和评估。
Mass spectrometry has become the analytical method of choice in metabolomics research. The identification of unknown compounds is the main bottleneck. In addition to the precursor mass, tandem MS spectra carry informative fragment peaks, but the coverage of spectral libraries of measured reference compounds are far from covering the complete chemical space. Compound libraries such as PubChem or KEGG describe a larger number of compounds, which can be used to compare their in silico fragmentation with spectra of unknown metabolites. We created the MetFrag suite to obtain a candidate list from compound libraries based on the precursor mass, subsequently ranked by the agreement between measured and in silico fragments. In the evaluation MetFrag was able to rank most of the correct compounds within the top 3 candidates returned by an exact mass query in KEGG. Compared to a previously published study, MetFrag obtained better results than the commercial MassFrontier software. Especially for large compound libraries, the candidates with a good score show a high structural similarity or just different stereochemistry, a subsequent clustering based on chemical distances reduces this redundancy. The in silico fragmentation requires less than a second to process a molecule, and MetFrag performs a search in KEGG or PubChem on average within 30 to 300 seconds, respectively, on an average desktop PC. We presented a method that is able to identify small molecules from tandem MS measurements, even without spectral reference data or a large set of fragmentation rules. With today's massive general purpose compound libraries we obtain dozens of very similar candidates, which still allows a confident estimate of the correct compound class. Our tool MetFrag improves the identification of unknown substances from tandem MS spectra and delivers better results than comparable commercial software. MetFrag is available through a web application, web services and as java library. The web frontend allows the end-user to analyse single spectra and browse the results, whereas the web service and console application are aimed to perform batch searches and evaluation.
登录
查看更多内容
DOI：
10.1021/ci025584y
发表时间：
2003-03
期刊：
Journal of chemical information and computer sciences
影响因子：
--
作者：
Steinbeck C;Han Y;Kuhn S;Horlacher O;Luttmann E;Willighagen E
通讯作者：
Willighagen E
DOI：
10.1016/1044-0305(94)87009-8
发表时间：
1994-09-01
影响因子：
3.2
作者：
STEIN, SE;SCOTT, DR
通讯作者：
SCOTT, DR
DOI：
10.1021/ci9803381
发表时间：
1999-07-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Butina, D
通讯作者：
Butina, D
影响因子：
2.5
作者：
Smith, CA;O'Maille, G;Siuzdak, G
通讯作者：
Siuzdak, G
影响因子：
5.8
作者：
Kopka, J;Schauer, N;Steinhauser, D
通讯作者：
Steinhauser, D