Imperial College London

DrMarinaEdelson-Averbukh

Faculty of Natural SciencesDepartment of Physics

Research Fellow in Mass Spectrometry
 
 
 
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Contact

 

m.edelson-averbukh

 
 
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Location

 

209Blackett LaboratorySouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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19 results found

Driver T, Averbukh V, Frasiński LJ, Marangos JP, Edelson-Averbukh Met al., 2021, Two-dimensional partial covariance mass spectrometry for the top-down analysis of intact proteins., Analytical Chemistry, Vol: 93, Pages: 10779-10788, ISSN: 0003-2700

Two-dimensional partial covariance mass spectrometry (2D-PC-MS) exploits the inherent fluctuations of fragment ion abundances across a series of tandem mass spectra, to identify correlated pairs of fragment ions produced along the same fragmentation pathway of the same parent (e.g., peptide) ion. Here, we apply 2D-PC-MS to the analysis of intact protein ions in a standard linear ion trap mass analyzer, using the fact that the fragment-fragment correlation signals are much more specific to the biomolecular sequence than one-dimensional (1D) tandem mass spectrometry (MS/MS) signals at the same mass accuracy and resolution. We show that from the distribution of signals on a 2D-PC-MS map it is possible to extract the charge state of both parent and fragment ions without resolving the isotopic envelope. Furthermore, the 2D map of fragment-fragment correlations naturally separates the products of the primary decomposition pathways of the molecular ions from those of the secondary ones. We access this spectral information using an adapted version of the Hough transform. We demonstrate the successful identification of highly charged, intact protein molecules bypassing the need for high mass resolution. Using this technique, we also perform the in silico deconvolution of the overlapping fragment ion signals from two co-isolated and co-fragmented intact proteins, demonstrating a viable new method for the concurrent mass spectrometric identification of a mixture of intact protein ions from the same fragment ion spectrum.

Journal article

Driver T, Bachhawat N, Frasinski L, Marangos J, Averbukh V, Edelson-Averbukh Met al., 2021, Chimera spectrum diagnostics for peptides using two-dimensional partial covariance mass spectrometry, Molecules, Vol: 26, ISSN: 1420-3049

The rate of successful identification of peptide sequences by tandem mass spectrometry (MS/MS) is adversely affected by the common occurrence of co-isolation and co-fragmentation of two or more isobaric or isomeric parent ions. This results in so-called `chimera spectra’, which feature peaks of the fragment ions from more than a single precursor ion. The totality of the fragment ion peaks in chimera spectra cannot be assigned to a single peptide sequence, which contradicts a fundamental assumption of the standard automated MS/MS spectra analysis tools, such as protein database search engines. This calls for a diagnostic method able to identify chimera spectra to single out the cases where this assumption is not valid. Here, we demonstrate that, within the recently developed two-dimensional partial covariance mass spectrometry (2D-PC-MS), it is possible to reliably identify chimera spectra directly from the two-dimensional fragment ion spectrum, irrespective of whether the co-isolated peptide ions are isobaric up to a finite mass accuracy or isomeric. We introduce ‘3-57 chimera tag’ technique for chimera spectrum diagnostics based on 2D-PC-MS and perform numerical simulations to examine its efficiency. We experimentally demonstrate the detection of a mixture of two isomeric parent ions, even under conditions when one isomeric peptide is at one five-hundredth of the molar concentration of the second isomer.

Journal article

Driver T, Cooper B, Ayers R, Pipkorn R, Patchkovskii S, Averbukh V, Klug D, Marangos J, Frasinski L, Edelson-Averbukh Met al., 2020, Two-dimensional partial covariance mass spectrometry of large molecules based on fragment correlations, Physical Review X, Vol: 10, Pages: 041004 – 1-041004 – 13, ISSN: 2160-3308

Covariance mapping [L. J. Frasinski, K. Codling, and P. A. Hatherly, Science 246, 1029 (1989)] is a well-established technique used for the study of mechanisms of laser-induced molecular ionization and decomposition. It measures statistical correlations between fluctuating signals of pairs of detected species (ions, fragments, electrons). A positive correlation identifies pairs of products originating from the same dissociation or ionization event. A major challenge for covariance-mapping spectroscopy is accessing decompositions of large polyatomic molecules, where true physical correlations are overwhelmed by spurious signals of no physical significance induced by fluctuations in experimental parameters. As a result, successful applications of covariance mapping have so far been restricted to low-mass systems, e.g., organic molecules of around 50 daltons (Da). Partial-covariance mapping was suggested to tackle the problem of spurious correlations by taking into account the independently measured fluctuations in the experimental conditions. However, its potential has never been realized for the decomposition of large molecules, because in these complex situations, determining and continuously monitoring multiple experimental parameters affecting all the measured signals simultaneously becomes unfeasible. We introduce, through deriving theoretically and confirming experimentally, a conceptually new type of partial-covariance mapping—self-correcting partial-covariance spectroscopy—based on a parameter extracted from the measured spectrum itself. We use the readily available total ion count as the self-correcting partial-covariance parameter, thus eliminating the challenge of determining experimental parameter fluctuations in covariance measurements of large complex systems. The introduced self-correcting partial covariance enables us to successfully resolve correlations of molecules as large as

Journal article

Katsanovskaja K, Driver T, Pipkorn R, Edelson-Averbukh Met al., 2019, Negative ion mode collision-induced dissociation for analysis of protein arginine methylation, Journal of the American Society for Mass Spectrometry, Vol: 30, Pages: 1229-1241, ISSN: 1044-0305

Arginine methylation is a common protein post-translational modification (PTM) that plays a key role in eukaryotic cells. Three distinct types of this modification are found in mammals: asymmetric Nη1Nη1-dimethylarginine (aDMA), symmetric Nη1Nη2-dimethylarginine (sDMA), and an intermediate Nη1-monomethylarginine (MMA). Elucidation of regulatory mechanisms of arginine methylation in living organisms requires precise information on both the type of the modified residues and their location inside the protein amino acid sequences. Despite mass spectrometry (MS) being the method of choice for analysis of multiple protein PTMs, unambiguous characterization of protein arginine methylation may not be always straightforward. Indeed, frequent internal basic residues of Arg methylated tryptic peptides hamper their sequencing under positive ion mode collision-induced dissociation (CID), the standardly used tandem mass spectrometry method, while the relative stability of the aDMA and sDMA side chains under alternative non-ergodic electron-based fragmentation techniques, electron-capture and electron transfer dissociations (ECD and ETD), may impede differentiation between the isobaric residues. Here, for the first time, we demonstrate the potential of the negative ion mode collision-induced dissociation MS for analysis of protein arginine methylation and present data revealing that the negative polarity approach can deliver both an unambiguous identification of the arginine methylation type and extensive information on the modified peptide sequences.

Journal article

Tittebrandt S, Edelson-Averbukh M, Spengler B, Lehmann WDet al., 2013, ESI Hydrogen/Deuterium Exchange Can Count Chemical Forms of Heteroatom-Bound Hydrogen, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 52, Pages: 8973-8975, ISSN: 1433-7851

Journal article

Edelson-Averbukh M, Shevchenko A, Pipkorn R, Lehmann WDet al., 2011, Discrimination Between Peptide O-Sulfo- and O-Phosphotyrosine Residues by Negative Ion Mode Electrospray Tandem Mass Spectrometry, JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, Vol: 22, Pages: 2256-2268, ISSN: 1044-0305

Journal article

Edelson-Averbukh M, Shevchenko A, Pipkorn R, Lehmann WDet al., 2009, Gas-Phase Intramolecular Phosphate Shift in Phosphotyrosine-Containing Peptide Monoanions, ANALYTICAL CHEMISTRY, Vol: 81, Pages: 4369-4381, ISSN: 0003-2700

Journal article

Edelson-Averbukh M, Pipkorn R, Lehmann WD, 2007, Analysis of protein phosphorylation in the regions of consecutive serine/threonine residues by negative ion electrospray collision-induced dissociation. Approach to pinpointing of phosphorylation sites, ANALYTICAL CHEMISTRY, Vol: 79, Pages: 3476-3486, ISSN: 0003-2700

Journal article

Lehmann W, Edelson-Averbukh M, 2005, Revival of negative ion electrospray tandem mass spectrometry in protein phosphorylation analysis, HUPO 4th Annual World Congress, Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA, Pages: S279-S279, ISSN: 1535-9476

Conference paper

Pereg Y, Shkedy D, de Graaf P, Meulmeester E, Edelson-Averbukh M, Salek M, Biton S, Teunisse AFAS, Lehmann WD, Jochemsen AG, Shiloh Yet al., 2005, Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 102, Pages: 5056-5061, ISSN: 0027-8424

Journal article

Kruger R, Hung CW, Edelson-Averbukh M, Lehmann WDet al., 2005, Iodoacetamide-alkylated methionine can mimic neutral loss of phosphoric acid from phosphopeptides as exemplified by nano-electrospray ionization quadrupole time-of-flight parent ion scanning, RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Vol: 19, Pages: 1709-1716, ISSN: 0951-4198

Journal article

Edelson-Averbukh M, Mandelbaum A, 2003, Intramolecular electrophilic aromatic substitution in gas-phase-protonated difunctional compounds containing one or two arylmethyl groups, JOURNAL OF MASS SPECTROMETRY, Vol: 38, Pages: 1169-1177, ISSN: 1076-5174

Journal article

Edelson-Averbukh M, Mandelbaum A, 2001, Stereospecific elimination of dihydropyran from protonated tetrahydropyranyl (THP) difunctional derivatives upon chemical ionization and collision-induced dissociation: intramolecular interactions in polyfunctional ions, INTERNATIONAL JOURNAL OF MASS SPECTROMETRY, Vol: 210, Pages: 545-556, ISSN: 1387-3806

Journal article

Edelson-Averbukh M, Mandelbaum A, 2000, Gas-phase intramolecular benzyl-benzyl interactions in protonated dibenzyl derivatives containing benzyl-oxygen, -sulfur and -nitrogen bonds, Journal of the Chemical Society-Perkin Transactions 2, Vol: 5, Pages: 989-996, ISSN: 0300-9580

Journal article

Edelson-Averbukh M, Etinger A, Mandelbaum A, 1999, Intramolecular benzyl-benzyl interactions in protonated benzyl diethers in the gas phase. Effects of internal hydrogen bonding, JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, Pages: 1095-1105, ISSN: 0300-9580

Journal article

Mandelbaum A, Edelson-Averbukh M, 1998, Chemistry and Stereochemistry of Intramolecular Multiple Benzyl-Benzyl Interactions in MH+ Ions of Oligo-Benzyl Derivatives upon Chemical Ionization and CID Conditions, Advances in Mass Spectrometry, Vol: 14, Pages: 1-12

Journal article

Edelson-Averbukh M, Mandelbaum A, 1997, Chemistry and Stereochemistry of Benzyl-Benzyl Interactions in MH+ Ions of Dibenzyl Esters upon Chemical Ionization and Collision-induced Dissociation Conditions, Journal of Mass Spectrometry, Vol: 32, Pages: 515-524, ISSN: 1076-5174

Journal article

Driver T, Ayers R, Pipkorn R, Cooper B, Bachhawat N, Patchkovskii S, Averbukh V, Klug DR, Marangos JP, Frasinski LJ, Edelson-Averbukh Met al., Partial covariance two-dimensional mass spectrometry for determination of biomolecular primary structure

Mass spectrometry (MS) is used widely in biomolecular structural analysis andis particularly dominant in the study of proteins. Despite its considerablepower, state-of-the-art protein MS frequently suffers from limited reliabilityof spectrum-to-structure assignments. This could not be solved fully by thedramatic increase in mass accuracy and resolution of modern MS instrumentationor by the introduction of new fragmentation methods. Here we present a new kindof two-dimensional mass spectrometry for high fidelity determination of abiomolecular primary structure based on partial covariance mapping. Partialcovariance two-dimensional mass spectrometry (pC-2DMS) detects intrinsicstatistical correlations between biomolecular fragments originating from thesame or consecutive decomposition events. This enables identification of pairsof ions produced along the same fragmentation pathway of a biomolecule acrossits entire fragment mass spectrum. We demonstrate that the fragment-fragmentcorrelations revealed by pC-2DMS provide much more specific information on theamino acid sequence and its covalent modifications than the individual fragmentmass-to-charge ratios on which standard one-dimensional MS is based. Weillustrate the power of pC-2DMS by using it to resolve structural isomers ofcombinatorially modified histone peptides inaccessible to standard MS.

Working paper

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