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Derive isotopic interference relationships

Source: R/isotope-derive.R
calc_isotopic_interferences.Rd

Automatically discovers isotopic (M+2) interference relationships between measured features and stores them in the annot_interferences slot, ready for correct_isotopic_interferences(). Two levels are supported:

  • "MRM" (default): fragment-based front/back correction for class-based LC-MRM data, derived from the LICAR method (see the manual). Requires precursor and product m/z and an mrm_pattern per feature.

  • "MS1": whole-molecule M+2 correction for MS1 / full-scan acquisitions. The factor is the M+2 relative abundance of each species' molecular formula; interfering pairs are matched by precursor m/z (~2 Da apart) within a feature class. Requires precursor m/z only.

Usage

calc_isotopic_interferences(
  data = NULL,
  level = c("MRM", "MS1"),
  mz_tol = 0.5,
  min_contribution = 0,
  check_coelution = FALSE
)

Arguments

data

A MRMhubExperiment object.

level

Correction level, "MRM" or "MS1". See description.

mz_tol

Precursor m/z tolerance (Da) for matching interfering pairs at the MS1 level (MRM uses a fixed 2 +/- 0.2 Da precursor window). Default 0.5.

min_contribution

Drop derived edges whose contribution factor K is below this value. Default 0 (keep all). Raise to skip negligible or borderline pairs (e.g. 0.002).

check_coelution

(experimental) If TRUE, an m/z-matched edge is kept only if the interferer and victim co-elute – the interferer's peak apex falls within the victim's integration window (imported borders feature_int_start/feature_int_end, else feature_rt +/- FWHM). Chromatographically resolved pairs are dropped. Default FALSE while the gate is validated.

Value

The MRMhubExperiment with a populated annot_interferences slot.

Details

Important — MS1 is not a fallback for MRM. For MRM data the isotopic correction must be fragment-based: the contribution of heavy isotopes to a transition depends on the isotope's location relative to the fragmentation (Gao et al. 2021). The whole-molecule ("MS1") level is only valid for genuine MS1/full-scan measurements and must not be used as a substitute for MRM data that happens to lack a product m/z.

Derived factors are sensitive to the enviPat version; version 2.8 is the reference. Existing manual interferences (source == "manual") are preserved; previously derived ("auto") rows are replaced.

How the contribution factor is computed

The contribution K is the fraction of a lighter species' signal that appears at M+2; it is subtracted downstream by correct_isotopic_interferences() as \(value_{corrected} = value_{raw} - K \cdot value_{interferer}\).

  • MS1 (whole-molecule): \(K = \sum ab(\text{peaks within } \pm 0.5 \text{ Da of } M_0 + 2)\, /\, ab(M_0)\), computed from the species' molecular formula with enviPat isopattern (see mN_rel_abundance()).

  • MRM (fragment-based, LICAR): the fragment elemental formula is built from the precursor carbon/hydrogen count plus a per-class offset c(C, H, O, N), with \(H = 2C + c_H - 2 H_{raw}\); K is that fragment's M+2 isotopologue fraction from enviPat isowrap (centroided, algorithm 2 — chosen over isopattern for parity with published LICAR values). Front vs back distinguishes whether the heavy isotope lands on the retained product ion or the neutral loss; FA/LCB species carry a front + back pair, and LCB inverts the front/back assignment relative to FA.

References

Gao L. et al. (2021). LICAR: An Application for Isotopic Correction of Targeted Lipidomic Data Acquired with Class-Based Chromatographic Separations Using Multiple Reaction Monitoring. Analytical Chemistry, 93(6), 3163-3171. doi:10.1021/acs.analchem.0c04565