Obtain transformation products (TPs) from formula annotation candidates

Transforms and prioritizes formula annotation candidates to obtain TPs.

Usage

generateTPsAnnForm(
  parents,
  formulas,
  minFitFormula = 0.94,
  skipInvalid = TRUE,
  prefCalcChemProps = TRUE,
  neutralChemProps = FALSE,
  parallel = TRUE
)

Arguments

parents

The parents for which transformation products should be obtained. This can be

a suspect list (see suspect screening for more information)
the output of screenSuspects in which case the suspects hits are used as parents

The parents need to have formula information available.

formulas

The formulas object containing the formula candidates.

minFitFormula

Minimum fitFormula (see Details sections) to filter out unlikely candidates.

skipInvalid

If set to TRUE then the parents will be skipped (with a warning) for which insufficient information (e.g. SMILES) is available.

prefCalcChemProps

If TRUE then calculated chemical properties such as the formula and InChIKey are preferred over what is already present in the parent suspect list. For efficiency reasons it is recommended to set this to TRUE. See the Validating and calculating chemical properties section for more details.

neutralChemProps

If TRUE then the neutral form of the molecule is considered to calculate SMILES, formulae etc. Enabling this may improve feature matching when considering common adducts (e.g. [M+H]+, [M-H]-). See the Validating and calculating chemical properties section for more details.

parallel

If set to TRUE then code is executed in parallel through the future package. Please see the parallelization section in the handbook for more details.

Value

generateTPsAnnForm returns an object of the class transformationProductsAnnForm. Please see its documentation for e.g. filtering steps that can be performed on this object.

Details

This function uses formula annotations to obtain transformation products. This function is called when calling generateTPs with algorithm="ann_form".

The generateTPsAnnForm function implements the unknown TP screening from formula candidates approach as described in (Helmus et al. 2025) . This algorithm does not rely on any known or predicted TPs and is therefore suitable for 'full non-target' workflows. All formula candidates are considered as potential TPs and are ranked by the TP score: $$TP score = fitFormula + annSim$$

With:

annSim: the annotation similarity
fitFormula: the common element count divided by the total element count for the formulae of the parent/TP or TP/parent (maximum is taken)

To speed up the calculation process, a threshold for fitFormula is applied to rule out unlikely candidates. The default was derived in (Helmus et al. 2025) .

Unlike most other TP generation algorithms, no additional suspect screening step is required.

Note

Setting parallel=TRUE may speed up calculations, but is only favorable for long calculations due to the overhead of setting up multiple R processes.

Validating and calculating chemical properties

Chemical properties such as SMILES, InChIKey and formulae in the parent suspect list are automatically validated and calculated if missing/invalid.

The internal validation/calculation process performs the following steps:

Validation of SMILES, InChI, InChIKey and formula data (if present). Invalid entries will be set to NA.
If neutralChemProps=TRUE then chemical data (SMILES, formulae etc.) is neutralized by (de-)protonation (using the –neutralized option of OpenBabel). An additional column molNeutralized is added to mark those molecules that were neutralized. Note that neutralization requires either SMILES or InChI data to be available.
The SMILES and InChI data are used to calculate missing or invalid SMILES, InChI, InChIKey and formula data. If prefCalcChemProps=TRUE then existing InChIKey and formula data is overwritten by calculated values whenever possible.
The chemical formulae which were not calculated are verified and normalized. This process may be time consuming, and is potentially largely avoided by setting prefCalcChemProps=TRUE.
Neutral masses are calculated for missing values (prefCalcChemProps=FALSE) or whenever possible (prefCalcChemProps=TRUE).

Note that calculation of formulae for molecules that are isotopically labelled is currently only supported for deuterium (2H) elements.

This functionality relies heavily on OpenBabel, please make sure it is installed.

References

OBoyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011). “Open Babel: An open chemical toolbox.” Journal of Cheminformatics, 3(1). doi:10.1186/1758-2946-3-33 .

Helmus R, Bagdonaite I, de Voogt P, van Bommel MR, Schymanski EL, van Wezel AP, ter Laak TL (2025). “Comprehensive Mass Spectrometry Workflows to Systematically Elucidate Transformation Processes of Organic Micropollutants: A Case Study on the Photodegradation of Four Pharmaceuticals.” Environmental Science & Technology, 59(7), 3723–3736. ISSN 1520-5851. doi:10.1021/acs.est.4c09121 . http://dx.doi.org/10.1021/acs.est.4c09121.