Gábor Transform-Based Signal Isolation, Rapid Deconvolution, and Quantitation of Intact Protein Ions with Mass Spectrometry DOI

Kayd L. Meldrum,

Andrew K. Swansiger,

Meghan M. Daniels

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(23), P. 9512 - 9523

Published: May 24, 2024

High-resolution mass spectrometry (HRMS) is a powerful technique for the characterization and quantitation of complex biological mixtures, with several applications including clinical monitoring tissue imaging. However, these medical pharmaceutical are pushing analytical limits modern HRMS techniques, requiring either further development in instrumentation or data processing methods. Here, we demonstrate new developments interactive Fourier-transform analysis (iFAMS) software first application Gábor transform (GT) to protein quantitation. Newly added automation tools detect signals from minimal user input apply thresholds signal selection, deconvolution, baseline correction improve objectivity reproducibility deconvolution. Additional were deconvolution highly congested spectra demonstrated here time. The "Gábor Slicer" enables explore trends spectrogram instantaneous ion estimates accurate 10 Da. charge adjuster allows easy visual confirmation state assignments quick adjustment if necessary. Deconvolution refinement utilizes second GT isotopically resolved remove common artifacts. To assess quality iFAMS, comparisons made deconvolutions using other algorithms such as UniDec an implementation MaxEnt Agilent MassHunter BioConfirm. Lastly, newly batch capabilities iFAMS compared extracted chromatogram approach.

Language: Английский

Computational tools and algorithms for ion mobility spectrometry‐mass spectrometry DOI Creative Commons
Dylan H. Ross, Harsh Bhotika, Xueyun Zheng

et al.

PROTEOMICS, Journal Year: 2024, Volume and Issue: 24(12-13)

Published: March 4, 2024

Abstract Ion mobility spectrometry‐mass spectrometry (IMS‐MS or IM‐MS) is a powerful analytical technique that combines the gas‐phase separation capabilities of IM with identification and quantification MS. IM‐MS can differentiate molecules indistinguishable masses but different structures (e.g., isomers, isobars, molecular classes, contaminant ions). The importance this reflected by staged increase in number applications for characterization across variety fields, from MS‐based omics (proteomics, metabolomics, lipidomics, etc.) to structural glycans, organic matter, proteins, macromolecular complexes. With increasing application there pressing need effective accessible computational tools. This article presents an overview most recent free open‐source software tools specifically tailored analysis interpretation data derived instrumentation. review enumerates these outlines their main algorithmic approaches, while highlighting representative fields. Finally, discussion current limitations expectable improvements presented.

Language: Английский

Citations

9
Fragment-based drug discovery campaigns guided by native mass spectrometry DOI
Louise M. Sternicki, Sally‐Ann Poulsen

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 15(7), P. 2270 - 2285

Published: Jan. 1, 2024

Native mass spectrometry (nMS) is well established as a biophysical technique for characterising biomolecules and their interactions with endogenous or investigational small molecule ligands such fragments.

Language: Английский

Citations

5
Expanding Native Mass Spectrometry to the Masses DOI
Sophie R. Harvey, Varun V. Gadkari, Brandon T. Ruotolo

et al.

Journal of the American Society for Mass Spectrometry, Journal Year: 2024, Volume and Issue: 35(3), P. 646 - 652

Published: Feb. 1, 2024

At the 33rd ASMS Sanibel Meeting, on Membrane Proteins and Their Complexes, a morning roundtable discussion was held discussing current challenges facing field of native mass spectrometry approaches to expanding nonexperts. This Commentary summarizes initiatives address these challenges.

Language: Английский

Citations

4
Discovering organic reactions with a machine-learning-powered deciphering of tera-scale mass spectrometry data DOI Creative Commons

Konstantin S. Kozlov,

Daniil A. Boiko, Julia V. Burykina

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 16, 2025

The accumulation of large datasets by the scientific community has surpassed capacity traditional processing methods, underscoring critical need for innovative and efficient algorithms capable navigating through extensive existing experimental data. Addressing this challenge, our study introduces a machine learning (ML)-powered search engine specifically tailored analyzing tera-scale high-resolution mass spectrometry (HRMS) This harnesses novel isotope-distribution-centric algorithm augmented two synergistic ML models, assisting with discovery hitherto unknown chemical reactions. methodology enables rigorous investigation data, thus providing support hypotheses while reducing conducting additional experiments. Moreover, we extend approach baseline methods automated reaction hypothesis generation. In its practical validation, successfully identified several reactions, unveiling previously undescribed transformations. Among these, heterocycle-vinyl coupling process within Mizoroki-Heck stands out, highlighting capability to elucidate complex phenomena. Mass generates vast amounts data in chemistry labs. Here, authors developed learning-driven that analyzes archived discover reactions without performing

Language: Английский

Citations

0
Online Buffer Exchange Enables Automated Membrane Protein Analysis by Native Mass Spectrometry DOI
Weijing Liu,

Hiruni S. Jayasekera,

James D. Sanders

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(47), P. 17212 - 17219

Published: Nov. 14, 2023

Membrane proteins represent the majority of clinical drug targets and are actively involved in a range cellular processes. However, complexity membrane mimetics for protein solubilization poses challenges native mass spectrometry (MS) analyses. The most common approach MS analyses remains offline buffer exchange into MS-compatible buffers prior to manual sample loading static nano-ESI emitters. This laborious process requires relatively high consumption optimization individual proteins. Here, we developed online coupled (OBE-nMS) analyzing different mimetics, including detergent micelles nanodiscs. Detergent screening OBE-nMS reveals that mobile phases containing ammonium acetate with lauryl-dimethylamine oxide universal characterizing both bacterial mammalian detergent. nanodiscs simply require as phase. To preserve intact nanodiscs, novel switching electrospray was used capture high-flow separation on column low-flow injection MS. Rapid completes each measurement within minutes thus enables higher-throughput assessment integrity its structural elucidation.

Language: Английский

Citations

8
High-Throughput Deconvolution of Native Protein Mass Spectrometry Imaging Data Sets for Mass Domain Analysis DOI Creative Commons
Oliver J. Hale, Helen J. Cooper, Michael T. Marty

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(37), P. 14009 - 14015

Published: Sept. 6, 2023

Protein mass spectrometry imaging (MSI) with electrospray-based ambient ionization techniques, such as nanospray desorption electrospray (nano-DESI), generates data sets in which each pixel corresponds to a spectrum populated by peaks corresponding multiply charged protein ions. Importantly, the signal associated is split among multiple charge states. These can be transformed into domain spectral deconvolution. When proteins are imaged under native/non-denaturing conditions retain non-covalent interactions, deconvolution particularly valuable helping interpret data. To improve acquisition speed, signal-to-noise ratio, and sensitivity, native MSI usually performed using resolving powers that do not provide isotopic resolution, conventional algorithms for of lower-resolution suitable these large sets. UniDec was originally developed enable rapid complex spectra. Here, we an updated feature set harnessing high-throughput module, MetaUniDec, deconvolve transform m/z-domain image files domain. New tools reading, processing, output open format .imzML downstream analysis. Transformation also provides greater accessibility, information readily interpretable users established biology sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Language: Английский

Citations

4
Gábor Transform-Based Signal Isolation, Rapid Deconvolution, and Quantitation of Intact Protein Ions with Mass Spectrometry DOI

Kayd L. Meldrum,

Andrew K. Swansiger,

Meghan M. Daniels

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(23), P. 9512 - 9523

Published: May 24, 2024

High-resolution mass spectrometry (HRMS) is a powerful technique for the characterization and quantitation of complex biological mixtures, with several applications including clinical monitoring tissue imaging. However, these medical pharmaceutical are pushing analytical limits modern HRMS techniques, requiring either further development in instrumentation or data processing methods. Here, we demonstrate new developments interactive Fourier-transform analysis (iFAMS) software first application Gábor transform (GT) to protein quantitation. Newly added automation tools detect signals from minimal user input apply thresholds signal selection, deconvolution, baseline correction improve objectivity reproducibility deconvolution. Additional were deconvolution highly congested spectra demonstrated here time. The "Gábor Slicer" enables explore trends spectrogram instantaneous ion estimates accurate 10 Da. charge adjuster allows easy visual confirmation state assignments quick adjustment if necessary. Deconvolution refinement utilizes second GT isotopically resolved remove common artifacts. To assess quality iFAMS, comparisons made deconvolutions using other algorithms such as UniDec an implementation MaxEnt Agilent MassHunter BioConfirm. Lastly, newly batch capabilities iFAMS compared extracted chromatogram approach.

Language: Английский

Citations

1