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. 2019 Apr 13;9(4):72.
doi: 10.3390/metabo9040072.

CFM-ID 3.0: Significantly Improved ESI-MS/MS Prediction and Compound Identification

Yannick Djoumbou-Feunang  1 , Allison Pon  2 , Naama Karu  3 , Jiamin Zheng  4 , Carin Li  5 , David Arndt  6 , Maheswor Gautam  7 , Felicity Allen  8 , David S Wishart  9   10
Affiliations

CFM-ID 3.0: Significantly Improved ESI-MS/MS Prediction and Compound Identification

Yannick Djoumbou-Feunang et al. Metabolites. .

Abstract

Metabolite identification for untargeted metabolomics is often hampered by the lack of experimentally collected reference spectra from tandem mass spectrometry (MS/MS). To circumvent this problem, Competitive Fragmentation Modeling-ID (CFM-ID) was developed to accurately predict electrospray ionization-MS/MS (ESI-MS/MS) spectra from chemical structures and to aid in compound identification via MS/MS spectral matching. While earlier versions of CFM-ID performed very well, CFM-ID's performance for predicting the MS/MS spectra of certain classes of compounds, including many lipids, was quite poor. Furthermore, CFM-ID's compound identification capabilities were limited because it did not use experimentally available MS/MS spectra nor did it exploit metadata in its spectral matching algorithm. Here, we describe significant improvements to CFM-ID's performance and speed. These include (1) the implementation of a rule-based fragmentation approach for lipid MS/MS spectral prediction, which greatly improves the speed and accuracy of CFM-ID; (2) the inclusion of experimental MS/MS spectra and other metadata to enhance CFM-ID's compound identification abilities; (3) the development of new scoring functions that improves CFM-ID's accuracy by 21.1%; and (4) the implementation of a chemical classification algorithm that correctly classifies unknown chemicals (based on their MS/MS spectra) in >80% of the cases. This improved version called CFM-ID 3.0 is freely available as a web server. Its source code is also accessible online.

Keywords: MS spectral prediction; combinatorial fragmentation; liquid chromatography; mass spectrometry; metabolite identification; rule-based fragmentation; structure-based chemical classification.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Fragmentation patterns of phosphatidylcholines obtained from their [M+H]+ precursor ions. Among all resulting fragments, only the precursor ion is observed at each of the three energy levels. The ion fragment C5H14NO4P+ (red arrow) corresponding to phosphocholine is observed at 20 and 40 eV, and the remaining fragments were observed only at 40 eV.
Figure 2
Figure 2
Head-to-tail plot of experimental and predicted electrospray ionization-tandem mass spectroscopy (ESI-MS/MS) spectra of PC(16:0/16:0). (a) Head-to-tail plot showing an experimental ESI-MS/MS spectrum of dipalmitoyl phosphatidylcholine (PC(16:0/16:0)) measured at 40 eV, and the matching ESI-MS/MS spectrum predicted by CFM-ID 2.0. The computed spectral similarity score is 0.07. (b) Head-to-tail plot showing an experimental of ESI-MS/MS spectrum of dipalmitoyl phosphatidylcholine measured in positive ion mode ([M+H]+) at 40 eV, and the matching ESI-MS/MS spectrum predicted by CFM-ID 3.0. The computed spectral similarity score is 0.88. (c) Head-to-tail plot showing an experimental of ESI-MS/MS spectrum of dipalmitoyl phosphatidylcholine measured in positive ion mode ([M+H]+) at 40 eV, and the matching ESI-MS/MS spectrum predicted by LipidBlast. The computed spectral similarity score is 0.13.
Figure 2
Figure 2
Head-to-tail plot of experimental and predicted electrospray ionization-tandem mass spectroscopy (ESI-MS/MS) spectra of PC(16:0/16:0). (a) Head-to-tail plot showing an experimental ESI-MS/MS spectrum of dipalmitoyl phosphatidylcholine (PC(16:0/16:0)) measured at 40 eV, and the matching ESI-MS/MS spectrum predicted by CFM-ID 2.0. The computed spectral similarity score is 0.07. (b) Head-to-tail plot showing an experimental of ESI-MS/MS spectrum of dipalmitoyl phosphatidylcholine measured in positive ion mode ([M+H]+) at 40 eV, and the matching ESI-MS/MS spectrum predicted by CFM-ID 3.0. The computed spectral similarity score is 0.88. (c) Head-to-tail plot showing an experimental of ESI-MS/MS spectrum of dipalmitoyl phosphatidylcholine measured in positive ion mode ([M+H]+) at 40 eV, and the matching ESI-MS/MS spectrum predicted by LipidBlast. The computed spectral similarity score is 0.13.
Figure 3
Figure 3
Head-to-tail plot of experimental and predicted ESI-MS/MS spectra of (PS(16:0/18:1(9Z))). (a) Head-to-tail plot showing an experimental of ESI-MS/MS spectrum of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (PS(16:0/18:1(9Z))) measured at 40 eV, and the matching ESI-MS/MS spectrum predicted by CFM-ID 2.0. The computed spectral similarity score is 0.10. (b) Head-to-tail plot showing an experimental ESI-MS/MS spectrum of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (PS(16:0/18:1(9Z))) measured at 40 eV, and the matching ESI-MS/MS spectrum predicted by CFM-ID 3.0. The computed similarity score is 0.92. (c) Head-to-tail plot showing an experimental ESI-MS/MS spectrum of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (PS(16:0/18:1(9Z))) measured at 40 eV, and the matching ESI-MS/MS spectrum predicted by LipidBlast. The computed similarity score is 0.91.
Figure 3
Figure 3
Head-to-tail plot of experimental and predicted ESI-MS/MS spectra of (PS(16:0/18:1(9Z))). (a) Head-to-tail plot showing an experimental of ESI-MS/MS spectrum of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (PS(16:0/18:1(9Z))) measured at 40 eV, and the matching ESI-MS/MS spectrum predicted by CFM-ID 2.0. The computed spectral similarity score is 0.10. (b) Head-to-tail plot showing an experimental ESI-MS/MS spectrum of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (PS(16:0/18:1(9Z))) measured at 40 eV, and the matching ESI-MS/MS spectrum predicted by CFM-ID 3.0. The computed similarity score is 0.92. (c) Head-to-tail plot showing an experimental ESI-MS/MS spectrum of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (PS(16:0/18:1(9Z))) measured at 40 eV, and the matching ESI-MS/MS spectrum predicted by LipidBlast. The computed similarity score is 0.91.
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