Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry.
Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry.
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DOI：
10.1186/1471-2105-8-105
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发表时间：
2007-03-27
影响因子：
3
通讯作者：
Fiehn O
中科院分区：
文献类型：
--
作者：
Kind T;Fiehn O
尽管在仪器方面取得了进展，但通过质谱法对未知小分子进行结构解析仍然是一个挑战。第一个关键步骤是获得正确的元素组成。为了自动约束数千种可能的候选结构，需要开发规则来选择最可能和化学正确的分子式。用于过滤分子式的算法源自七个启发式规则：（1）对元素数目的限制，（2）刘易斯和SENIOR化学规则，（3）同位素模式，（4）氢/碳比，（5）氮、氧、磷和硫与碳的元素比，（6）元素比概率和（7）三甲基甲硅烷基化化合物的存在。公式根据其同位素模式进行排名，随后受到公共化学数据库中存在的限制。这七条规则是根据68，237个现有分子式制定的，并在四个实验中得到验证。首先，检查了涵盖500万PubChem数据库条目的432，968个公式的一致性。这些化合物中只有0.6%没有通过所有规则。接下来，这些规则被证明可以有效地将高达2000 Da的所有80亿个理论上可能的C、H、N、S、O、P公式减少到只有6.23亿个最可能的元素组成。第三，从DrugBank，TSCA和DNP数据库中选择了6，000种药物，有毒和天然化合物。当假设数据采集具有独特化合物的完全分辨率和5%绝对同位素比偏差和3 ppm质量精度时，以80-99%的概率检索正确的公式作为最高命中。最后，通过傅立叶变换离子回旋共振质谱法和气相色谱-飞行时间质谱法分析了一些示例性化合物。在每种情况下，当将七条规则与数据库查询相结合时，正确的公式都被列为最佳答案。这七条规则能够自动排除错误的分子式或包含不太可能的高或低数量的元素的分子式。如果分子式存在于化合物数据库中，则以98%的概率分配正确的分子式。对于数据库中不存在的真正的新化合物，在前三次命中中找到正确的公式的概率为65- 81%。相应的软件和补充数据可从作者的网站下载。
Structure elucidation of unknown small molecules by mass spectrometry is a challenge despite advances in instrumentation. The first crucial step is to obtain correct elemental compositions. In order to automatically constrain the thousands of possible candidate structures, rules need to be developed to select the most likely and chemically correct molecular formulas. An algorithm for filtering molecular formulas is derived from seven heuristic rules: (1) restrictions for the number of elements, (2) LEWIS and SENIOR chemical rules, (3) isotopic patterns, (4) hydrogen/carbon ratios, (5) element ratio of nitrogen, oxygen, phosphor, and sulphur versus carbon, (6) element ratio probabilities and (7) presence of trimethylsilylated compounds. Formulas are ranked according to their isotopic patterns and subsequently constrained by presence in public chemical databases. The seven rules were developed on 68,237 existing molecular formulas and were validated in four experiments. First, 432,968 formulas covering five million PubChem database entries were checked for consistency. Only 0.6% of these compounds did not pass all rules. Next, the rules were shown to effectively reducing the complement all eight billion theoretically possible C, H, N, S, O, P-formulas up to 2000 Da to only 623 million most probable elemental compositions. Thirdly 6,000 pharmaceutical, toxic and natural compounds were selected from DrugBank, TSCA and DNP databases. The correct formulas were retrieved as top hit at 80–99% probability when assuming data acquisition with complete resolution of unique compounds and 5% absolute isotope ratio deviation and 3 ppm mass accuracy. Last, some exemplary compounds were analyzed by Fourier transform ion cyclotron resonance mass spectrometry and by gas chromatography-time of flight mass spectrometry. In each case, the correct formula was ranked as top hit when combining the seven rules with database queries. The seven rules enable an automatic exclusion of molecular formulas which are either wrong or which contain unlikely high or low number of elements. The correct molecular formula is assigned with a probability of 98% if the formula exists in a compound database. For truly novel compounds that are not present in databases, the correct formula is found in the first three hits with a probability of 65–81%. Corresponding software and supplemental data are available for downloads from the authors' website.
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影响因子：
15
作者：
BUCHANAN, BG;SMITH, DH;DJERASSI, C
通讯作者：
DJERASSI, C
影响因子：
--
作者：
Dempster, AJ
通讯作者：
Dempster, AJ
DOI：
10.1002/0471720895.ch3
发表时间：
2005-01-01
期刊：
REVIEWS IN COMPUTATIONAL CHEMISTRY, VOL 21
影响因子：
--
作者：
Faulon, JL;Visco, DP;Roe, D
通讯作者：
Roe, D
DOI：
10.1021/ci0341060
发表时间：
2004-05-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Elyashberg, ME;Blinov, KA;Martirosian, ER
通讯作者：
Martirosian, ER
影响因子：
7.4
作者：
Fiehn, O;Kopka, J;Willmitzer, L
通讯作者：
Willmitzer, L