Neutral mass derivation from mz

neutral-mass-derivation-from-mz

Summary

Converts observed m/z values to neutral molecular mass by applying the inverse of configured adduct transformations (e.g., [M+H]+, [M+Na]+, [M-H]−). This step precedes formula database lookup and is essential for disambiguating which molecular formula corresponds to each observed peak.

When to use

Apply this skill after adduct configuration is complete and before querying formula databases. Use it whenever you have m/z peak lists from mass spectrometry data and need to identify the neutral mass underlying each observed ion, particularly when multiple adduct types are active in the same experiment.

When NOT to use

• Input m/z values are already neutral masses or have been pre-converted by external software—re-applying this skill will introduce double-correction errors.
• Adduct configuration has not been defined; attempting neutral mass derivation without adduct parameters will produce nonsensical results.
• You are working with intact molecular ion peaks that require no adduct correction (rare in typical LC-MS/MS workflows, but possible in some direct-injection experiments).

Inputs

• m/z peak list (numeric array or table with m/z column)
• adduct configuration table (adduct names, masses, charge states)
• mass spectrometry mode (positive or negative ionization)

Outputs

• neutral mass value per peak (numeric)
• adduct type assignment per peak (string, e.g. '[M+H]+', '[M+Na]+', '[M-H]−')
• tabulated results (observed m/z, neutral mass, adduct type, optional: mass error vs. reference if available)

How to apply

For each configured adduct type (e.g., [M+H]+, [M+Na]+, [M-H]−), calculate the neutral mass by subtracting the adduct mass and restoring any lost or gained protons/electrons. For example, to recover neutral mass from [M+H]+ at observed m/z 400, subtract 1.00783 Da (proton mass); for [M+Na]+ at m/z 420, subtract 22.98977 Da (sodium mass minus proton). Apply this transformation to all peaks in the m/z peak list. The rationale is that metabolite databases store neutral masses; matching observed ions to database entries requires first recovering the neutral parent. Store results as neutral mass per peak, tagged with the inferred adduct type for traceability.

Related tools

• MetaboShiny (Integrated shiny application that orchestrates adduct configuration and neutral mass derivation as part of the formula prediction and lookup workflow step.) — https://github.com/joannawolthuis/MetaboShiny
• R (Primary scripting language used to implement adduct transformation calculations and mass arithmetic within MetaboShiny.)

Evaluation signals

• Verify that neutral masses are mathematically correct: for each observed m/z and adduct pair, check that neutral_mass = observed_m_z - adduct_delta (or + for negative adducts), where adduct_delta is from the configured adduct table.
• Confirm that neutral masses fall within the expected biochemical range for the organism/sample type (typically 50–2000 Da for small metabolites).
• Check that the distribution of mass errors (theoretical neutral mass from a reference database minus derived neutral mass) is centered near zero and has width consistent with the configured ppm tolerance (e.g., ±5 ppm).
• Cross-validate: re-derive m/z from the output neutral mass and adduct type; result should match the input observed m/z within measurement precision.
• Ensure no peaks are lost or duplicated; count of output neutral mass records should equal count of input m/z peaks (one neutral mass per peak per adduct type tested).

Limitations

• Adduct table must be accurate and complete; missing or incorrectly specified adduct masses will propagate errors into all downstream formula matching steps.
• Neutral mass derivation assumes that the observed m/z corresponds to exactly one of the configured adducts; ambiguous cases (e.g., overlapping m/z from different adducts of similar mass) require additional disambiguation logic not covered by this skill alone.
• High-mass peaks (m/z > 1000) or multiply charged ions (z > 1) require correct charge state specification in the adduct definition; the skill does not auto-detect charge.
• In-source fragmentation or unknown neutral loss can produce observed m/z values that do not correspond to any configured adduct; such peaks cannot be converted and may require manual inspection or filtering.

Evidence

• [other] For each m/z value, calculate the neutral mass by applying the inverse of each configured adduct transformation (e.g., [M+H]+, [M+Na]+, [M-H]−).: "For each m/z value, calculate the neutral mass by applying the inverse of each configured adduct transformation (e.g., [M+H]+, [M+Na]+, [M-H]−)."
• [other] Formula prediction and lookup module positioned after adduct configuration in the analysis pipeline.: "positioned after adduct configuration and before isotope scoring in the analysis pipeline"
• [readme] Adduct configuration table with current definitions and rules for adduct calculation.: "The "Definitions" tab shows the current adduct table. Below the table is a field to import another adduct table. The "Rules" field shows the adduct rules that are used to calculate adducts when"
• [other] Return neutral masses tagged with adduct type and theoretical m/z for validation.: "Return and tabulate the top-ranked candidates with their assigned formula, adduct type, observed m/z, theoretical m/z, and mass error for each peak."