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Protein identity + site-specific modifications — measured on the intact molecule, not inferred from fragments.
One protein can have dozens of proteoforms, making peptide proteomics a guessing game. The gene tells you the sequence. It does not tell you which residues are cut, phosphorylated, glycosylated or ubiquitinated — nor which of those happen on the same molecule at the same time.
That combination is the proteoform. It is the molecule that actually does the biology, and it is the only level at which a modification pattern can be read as a single, coherent measurement.
This J Proteome Res paper explains why understanding proteoforms with peptides is impossible.
The molecule is digested first. Each peptide reports on its own small window, so co-occurring modifications on the same molecule are unrecoverable — you get an average over a population you never observed. Truncation sites and proteoform ratios are inferred, not measured.
The whole molecule enters the instrument. Identity, modification sites and their combinations are read off one species, and single-particle detection means low-abundance proteoforms are not buried by the ensemble. What you report is what was in the specimen.
Measuring one ion at a time resolves species that overlap hopelessly in an ensemble spectrum — up to and beyond megadalton complexes.
Individual ion MS raises sensitivity and sequence coverage in top-down experiments, so modest amounts of precious material still yield a readable proteoform landscape.
Isotopic resolution has been demonstrated on protein complexes up to 466 kDa, and robust charge-detection platforms extend the range to megadalton biotherapeutics.
Multiplexed measurement of individual ions improves how precisely proteoforms — and their complexes — can be quantified side by side in one run.
Let’s figure it out together. Tell us the specimen and the question — we’ll tell you whether proteoforms can answer it.