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@ARTICLE{Driver:276354,
author = {T. Driver and R. Pipkorn$^*$ and V. Averbukh and L. J.
Frasinski and J. P. Marangos and M. Edelson-Averbukh},
title = {{I}dentification of {C}ofragmented {C}ombinatorial
{P}eptide {I}somers by {T}wo-{D}imensional {P}artial
{C}ovariance {M}ass {S}pectrometry.},
journal = {Journal of the American Society for Mass Spectrometry},
volume = {34},
number = {7},
issn = {1044-0305},
address = {Washington, DC},
publisher = {ACS Publications},
reportid = {DKFZ-2023-01074},
pages = {1230-1234},
year = {2023},
note = {2023 Jul 5;34(7):1230-1234},
abstract = {Combinatorial post-translational modifications (PTMs), such
as those forming the so-called 'histone code', have been
linked to cell differentiation, embryonic development,
cellular reprogramming, aging, cancers, neurodegenerative
disorders, etc. Nevertheless, a reliable mass spectral
analysis of the combinatorial isomers represents a
considerable challenge. The difficulty stems from the
incompleteness of information that could be generated by the
standard MS to differentiate cofragmented isomeric sequences
in their naturally occurring mixtures based on the fragment
mass-to-charge ratio and relative abundance information
only. Here we show that fragment-fragment correlations
revealed by two-dimensional partial covariance mass
spectrometry (2D-PC-MS) allow one to solve the combinatorial
PTM puzzles that cannot be tackled by the standard MS as a
matter of principle. We introduce 2D-PC-MS marker ion
correlation approach and demonstrate experimentally that it
can provide the missing information enabling identification
of cofragmentated combinatorially modified isomers. Our in
silico study shows that the marker ion correlations can be
used to unambiguously identify 5 times more cofragmented
combinatorially acetylated tryptic peptides and 3 times more
combinatorially modified Glu-C peptides of human histones
than is possible using standard MS methods.},
keywords = {2D-PC-MS (Other) / combinatorial PTMs (Other) / histones
(Other) / marker ion correlations (Other) / mass
spectrometry (Other)},
cin = {D015},
ddc = {530},
cid = {I:(DE-He78)D015-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37252811},
doi = {10.1021/jasms.3c00111},
url = {https://inrepo02.dkfz.de/record/276354},
}