Mass difference matching unfolds hidden molecular structures of dissolved organic matter

06 June 2022, Version 3
This content is a preprint and has not undergone peer review at the time of posting.


Ultrahigh-resolution Fourier transform mass spectrometry (FTMS) has revealed unprecedented detail of natural complex mixtures such as dissolved organic matter (DOM) on a molecular formula level, but we lack approaches to access the underlying structural complexity. We here explore the hypothesis that every DOM precursor ion is potentially linked with all emerging product ions in FTMS2 experiments. The resulting mass difference (Δm) matrix is deconvoluted to isolate individual precursor ion Δm profiles and matched with structural information, which was derived from 42 Δm features from 14 in-house reference compounds and a global set of 11477 Δm features with assigned structure specificities, using a dataset of ~18000 unique structures. We show that Δm matching is highly sensitive in predicting potential precursor ion identities in terms of molecular and structural composition. Additionally, the approach identified unresolved precursor ions and missing elements in molecular formula annotation (P, Cl, F). Our study provides first results how Δm matching refines structural annotations in Van Krevelen space, but simultaneously demonstrates the wide overlap between potential structural classes. We show that this effect is likely driven by chemodiversity and offers an explanation for the observed ubiquitous presence of molecules in the center of the Van Krevelen space. Our promising first results suggest that Δm matching can both unfold the structural information encrypted in DOM and assess the quality of FTMS-derived molecular formulas of complex mixtures in general.


Natural Organic Matter
Tandem mass spectrometry

Supplementary materials

Supporting Information
This Supporting Information file belongs to the working paper "Mass difference matching unfolds hidden molecular structures of dissolved organic matter" by Carsten Simon, Kai Dührkop, Daniel Petras, Vanessa-Nina Roth, Sebastian Böcker, Pieter Dorrestein and Gerd Gleixner. It contains 22 supporting tables (Table S1 to S22), 13 supporting figures (Figures S1 to S13), six supporting text resources (Note S1 to S6), two supporting data sets (Data Sets S1 to S2) and 78 references. Data Set S1 is available via the MASSIVE repository, Data Set S2 is under revision on PANGAEA and will become openly available upon publication. Until then, Data Set S2 is available only upon personal request to Dr. Carsten Simon ([email protected]).

Supplementary weblinks


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.