MS2‐Deisotoper: A Tool for Deisotoping High‐Resolution MS/MS Spectra in Normal and Heavy Isotope‐Labelled Samples

Tay, Aidan P.; Liang, Angelita; Hamey, Joshua J.; Hart‐Smith, Gene; Wilkins, Marc R.

doi:10.1002/pmic.201800444

Cited by 4 publications

(6 citation statements)

References 59 publications

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“…This was not unexpected, as the density of theoretical fragment masses is sufficiently low in a closed search for the extra spectral peaks included when forgoing deisotoping to be unlikely to match to incorrect peptides frequently enough to generate high-scoring false positives and reduce the sensitivity of the search. This is in contrast to results from MS2Deisotoper, which increased PSMs found by 3.5% for a typical closed search. MSFragger performs several spectral processing steps, including mass calibration to enable the use of a narrow fragment mass tolerance and considering only the top N peaks in each spectrum (150 by default).…”

Section: Resultscontrasting

confidence: 99%

“…Deisotoping speed was compared by analyzing the Chick et al dataset with MSFragger, MS2Deisotoper, and HardKlor. , Default parameters were used for MS2Deisotoper and MSFragger. HardKlor parameters were default except only MS2 spectra were deisotoped, data was precentroided, and the instrument was set to Orbitrap, resolution 17 500, to match the input data.…”

Section: Methodsmentioning

confidence: 99%

“…Deisotoping speed was compared by analyzing the Chick et al dataset with MSFragger, MS2Deisotoper, 10 and HardKlor. 18,33 Default parameters were used for MS2Deisotoper and MSFragger.…”

Section: Comparison With Other Deisotoping Toolsmentioning

confidence: 99%

“…There are several factors that make deisotoping a challenging task, including the overlap of isotopic cluster signals, noise and other variations in peak intensity, and the need to approximate the expected isotopic abundance pattern. Because the identity and chemical composition of peptide and fragment ions is not known prior to database searching, deisotoping tools for proteomics do not know the exact isotope distribution to expect for a given peak cluster and must either do without, by simple filtering of peaks that appear at the m / z spacing(s) corresponding to the mass difference between isotopes, − or make an educated guess. The averagine model has been the predominant guess used for peptide and protein isotopic patterns for several decades, and assigning peaks to clusters and comparing those clusters to the averagine distribution at a given m / z the typical approach to deisotoping. − …”

Section: Introductionmentioning

confidence: 99%

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Fast Deisotoping Algorithm and Its Implementation in the MSFragger Search Engine

et al. 2020

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Deisotoping, or the process of removing peaks in a mass spectrum resulting from the incorporation of naturally occurring heavy isotopes, has long been used to reduce complexity and improve the effectiveness of spectral annotation methods in proteomics. We have previously described MSFragger, an ultrafast search engine for proteomics, that did not utilize deisotoping in processing input spectra. Here, we present a new, high-speed parallelized deisotoping algorithm, based on elements of several existing methods, that we have incorporated into the MSFragger search engine. Applying deisotoping with MSFragger reveals substantial improvements to database search speed and performance, particularly for complex methods like open or nonspecific searches. Finally, we evaluate our deisotoping method on data from several instrument types and vendors, revealing a wide range in performance and offering an updated perspective on deisotoping in the modern proteomics environment.

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Section: Resultscontrasting

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Deisotoping speed was compared by analyzing the Chick et al dataset with MSFragger, MS2Deisotoper, 10 and HardKlor. 18,33 Default parameters were used for MS2Deisotoper and MSFragger.…”

Section: Comparison With Other Deisotoping Toolsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fast Deisotoping Algorithm and Its Implementation in the MSFragger Search Engine

et al. 2020

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“…Error tolerance thresholds for the parent and fragment ion masses turned out to be of significant influence on the identified peptides and the modifications. This is essential because only mass differences are used for identification of the chlorine PTMs, while other relevant information, such as the isotope pattern, is not incorporated as this can hamper protein identification rates. , In addition, the isomers of Y(Cl)LYEIAR and Y(Cl)LY(Cl 2 )EIAR were only found manually due to their trace level and the applied concentration threshold settings.…”

Section: Resultsmentioning

confidence: 99%

Elucidation of in Vitro Chlorinated Tyrosine Adducts in Blood Plasma as Selective Biomarkers of Chlorine Exposure

Bruin-Hoegée

Damme

Groningen

et al. 2022

Chem. Res. Toxicol.

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Chlorine is a widely available industrial chemical and involved in a substantial number of cases of poisoning. It has also been used as a chemical warfare agent in military conflicts. To enable forensic verification, the persistent biomarkers 3-chlorotyrosine and 3,5-dichlorotyrosine in biomedical samples could be detected. An important shortfall of these biomarkers, however, is the relatively high incidence of elevated levels of chlorinated tyrosine residues in individuals with inflammatory diseases who have not been exposed to chlorine. Therefore, more reliable biomarkers are necessary to distinguish between endogenous formation and exogeneous exposure. The present study aims to develop a novel diagnostic tool for identifying site-specific chlorinated peptides as a more unambiguous indicator of exogeneous chlorine exposure. Human blood plasma was exposed in vitro to various chlorine concentrations, and the plasma proteins were subsequently digested by pronase, trypsin, or pepsin. After sample preparation, the digests were analyzed by liquid chromatography tandem mass spectrometry (LC–MS/MS) and liquid chromatography high-resolution tandem mass spectrometry (LC–HRMS/MS). In line with other studies, low levels of 3-chlorotyrosine and 3,5-dichlorotyrosine were found in blank plasma samples in this study. Therefore, 50 site-specific biomarkers were identified, which could be used as more unambiguous biomarkers for chlorine exposure. Chlorination of the peptides TY*ETTLEK, Y*KPGQTVK, Y*QQKPGQAPR, HY*EGSTVPEK, and Y*LY*EIAR could already be detected at moderate in vitro chlorine exposure levels. In addition, the latter two peptides were found to have dichlorinated fragments. Especially, Y*LY*EIAR, with a distinct chlorination pattern in the MS spectra, could potentially be used to differentiate exogeneous exposure from endogenous causes as other studies reported that this part of human serum albumin is nitrated rather than chlorinated under physiological conditions. In conclusion, trypsin digestion combined with high-resolution MS analysis of chlorinated peptides could constitute a valuable technique for the forensic verification of exposure to chlorine.

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The isotope distribution: A rose with thorns

Claesen

Rockwood

Горшков

et al. 2023

Mass Spectrometry Reviews

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The isotope distribution, which reflects the number and probabilities of occurrence of different isotopologues of a molecule, can be theoretically calculated. With the current generation of (ultra)‐high‐resolution mass spectrometers, the isotope distribution of molecules can be measured with high sensitivity, resolution, and mass accuracy. However, the observed isotope distribution can differ substantially from the expected isotope distribution. Although differences between the observed and expected isotope distribution can complicate the analysis and interpretation of mass spectral data, they can be helpful in a number of specific applications. These applications include, yet are not limited to, the identification of peptides in proteomics, elucidation of the elemental composition of small organic molecules and metabolites, as well as wading through peaks in mass spectra of complex bioorganic mixtures such as petroleum and humus. In this review, we give a nonexhaustive overview of factors that have an impact on the observed isotope distribution, such as elemental isotope deviations, ion sampling, ion interactions, electronic noise and dephasing, centroiding, and apodization. These factors occur at different stages of obtaining the isotope distribution: during the collection of the sample, during the ionization and intake of a molecule in a mass spectrometer, during the mass separation and detection of ionized molecules, and during signal processing.

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MS2‐Deisotoper: A Tool for Deisotoping High‐Resolution MS/MS Spectra in Normal and Heavy Isotope‐Labelled Samples

Cited by 4 publications

References 59 publications

Fast Deisotoping Algorithm and Its Implementation in the MSFragger Search Engine

Fast Deisotoping Algorithm and Its Implementation in the MSFragger Search Engine

Elucidation of in Vitro Chlorinated Tyrosine Adducts in Blood Plasma as Selective Biomarkers of Chlorine Exposure

The isotope distribution: A rose with thorns

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