Advances in data‐independent acquisition mass spectrometry towards comprehensive digital proteome landscape

Abstract

The data‐independent acquisition mass spectrometry (DIA‐MS) has rapidly evolved as a powerful alternative for highly reproducible proteome profiling with a unique strength of generating permanent digital maps for retrospective analysis of biological systems. Recent advancements in data analysis software tools for the complex DIA‐MS/MS spectra coupled to fast MS scanning speed and high mass accuracy have greatly expanded the sensitivity and coverage of DIA‐based proteomics profiling. Here, we review the evolution of the DIA‐MS techniques, from earlier proof‐of‐principle of parallel fragmentation of all‐ions or ions in selected m/z range, the sequential window acquisition of all theoretical mass spectra (SWATH‐MS) to latest innovations, recent development in computation algorithms for data informatics, and auxiliary tools and advanced instrumentation to enhance the performance of DIA‐MS. We further summarize recent applications of DIA‐MS and experimentally‐derived as well as in silico spectra library resources for large‐scale profiling to facilitate biomarker discovery and drug development in human diseases with emphasis on the proteomic profiling coverage. Toward next‐generation DIA‐MS for clinical proteomics, we outline the challenges in processing multi‐dimensional DIA data set and large‐scale clinical proteomics, and continuing need in higher profiling coverage and sensitivity.

MSBooster: Improving Peptide Identification Rates using Deep Learning-Based Features

“…In the second stage of MS analysis, selected (typically the most intense) peptide ions are subjected to isolation and fragmentation to break the peptide bond [3] (data independent acquisition (DDA) approach). Alternatively, all peptide ions within a wider (e.g., 10 Da) window of m/z values (data independent acquisition, DIA) [4] or in a continuous quadrupole scan of a particular window size [5] are selected for simultaneous fragmentation. The resulting MS/MS spectra, whether generated in the DIA or DDA mode, contain m/z values, intensities and IM values (when applicable) of all observed fragment ions (e.g., y- and b-ions when using higher energy collisional dissociation, HCD, fragmentation) for the precursor peptides subjected to MS/MS.…”

Proteomic insights into SARS-CoV-2 infection mechanisms, diagnosis, therapies and prognostic monitoring methods

“…Simultaneous marker quantification is now possible for up to 16 markers, making it particularly suitable for differential proteomic analysis of COVID-19 samples using multiple treatments or from multiple treatment times. Data-independent acquisition (DIA) is a commonly used label-free quantification method, such as the sequential window acquisition of all theoretical fragment ions (SWATH) for large-scale label-free quantification, which can efficiently determine protein molecules of very low abundance in complex samples with good reproducibility ( 39 ). The advent of another revolutionary new method, parallel accumulation serial fragmentation (PASEF), has endowed shotgun proteomics with greater speed and sensitivity, making it more suitable for the analysis of microsamples ( 40 ).…”

Mass Spectrometry-Based Techniques Towards OMICS 2.0

“…Aside its unique strength in performing analysis, MS has a remarkable ability of generating permanent collections of digital content for retrospective analysis [94]. Substances such as antibiotics, immunesuppressive drugs, drug metabolites in former addicts, or therapeutic antibodies used for the treatment of different diseases can all be tracked by the MS. High-resolution, mass-accurate data can demand infrastructure capable of managing 1 GB/h of data.…”