Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools—Chances and Limitations: A Critical Review DOI Open Access
Joachim Müller, Ghalia Boubaker,

Norbert Müller

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6903 - 6903

Published: June 24, 2024

Identification of drug targets and biochemical investigations on mechanisms action are major issues in modern development. The present article is a critical review the classical "one drug"-"one target" paradigm. In fact, novel methods for target deconvolution investigation resistant strains based protein mass spectrometry have shown that multiple gene products adaptation involved responses pathogens to xenobiotics rather than one single or product. Resistance drugs may be linked differential expression other proteins those interacting with binding studies result complex cell physiological adaptation. Consequently, unraveling needs approaches beyond proteomics. This focused protozoan pathogens. conclusions can, however, extended chemotherapies against cancer.

Language: Английский

TIMS2Rescore: A Data Dependent Acquisition-Parallel Accumulation and Serial Fragmentation-Optimized Data-Driven Rescoring Pipeline Based on MS2Rescore DOI Creative Commons
Arthur Declercq, Robbe Devreese, Jonas Scheid

et al.

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

The high throughput analysis of proteins with mass spectrometry (MS) is highly valuable for understanding human biology, discovering disease biomarkers, identifying therapeutic targets, and exploring pathogen interactions. To achieve these goals, specialized proteomics subfields, including plasma proteomics, immunopeptidomics, metaproteomics, must tackle specific analytical challenges, such as an increased identification ambiguity compared to routine experiments. Technical advancements in MS instrumentation can mitigate issues by acquiring more discerning information at higher sensitivity levels. This exemplified the incorporation ion mobility parallel accumulation serial fragmentation (PASEF) technologies timsTOF instruments. In addition, AI-based bioinformatics solutions help overcome integrating data into workflow. Here, we introduce TIMS2Rescore, a data-driven rescoring workflow optimized DDA-PASEF from platform includes new MS2PIP spectrum prediction models IM2Deep, deep learning-based peptide predictor. Furthermore, fully streamline throughput, TIMS2Rescore directly accepts Bruker raw search results ProteoScape many other engines, Sage PEAKS. We showcase performance on immunopeptidomics (HLA class I II), metaproteomics sets. open-source freely available https://github.com/compomics/tims2rescore.

Language: Английский

Citations

2
Koina: Democratizing machine learning for proteomics research DOI Creative Commons
Ludwig Lautenbacher, Kevin Yang, Tobias Kockmann

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Abstract Recent developments in machine-learning (ML) and deep-learning (DL) have immense potential for applications proteomics, such as generating spectral libraries, improving peptide identification, optimizing targeted acquisition modes. Although new ML/DL models various properties are frequently published, the rate at which these adopted by community is slow, mostly due to technical challenges. We believe that, make better use of state-of-the-art models, more attention should be spent on making easy accessible community. To facilitate this, we developed Koina, an open-source containerized, decentralized online-accessible high-performance prediction service that enables model usage any pipeline. Using widely used FragPipe computational platform example, show how Koina can easily integrated with existing proteomics software tools integrations improve data analysis.

Language: Английский

Citations

9
High-quality peptide evidence for annotating non-canonical open reading frames as human proteins DOI Creative Commons
Eric W. Deutsch, Leron W. Kok, Jonathan M. Mudge

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

A major scientific drive is to characterize the protein-coding genome as it provides primary basis for study of human health. But fundamental question remains: what has been missed in prior genomic analyses? Over past decade, translation non-canonical open reading frames (ncORFs) observed across cell types and disease states, with implications proteomics, genomics, clinical science. However, impact ncORFs limited by absence a large-scale understanding their contribution proteome. Here, we report collaborative efforts stakeholders immunopeptidomics, Ribo-seq ORF discovery, gene annotation, produce consensus landscape protein-level evidence ncORFs. We show that at least 25% set 7,264 give rise translated products, yielding over 3,000 peptides pan-proteome analysis encompassing 3.8 billion mass spectra from 95,520 experiments. With these data, developed an annotation framework created public tools researchers through GENCODE PeptideAtlas. This work will provide platform advance ncORF-derived proteins biomedical discovery and, beyond humans, diverse animals plants where are similarly observed.

Language: Английский

Citations

8
Immunopeptidomics for autoimmunity: unlocking the chamber of immune secrets DOI Creative Commons

Sanya Arshad,

Benjamin Cameron,

Alok V. Joglekar

et al.

npj Systems Biology and Applications, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 17, 2025

T cells mediate pathogenesis of several autoimmune disorders by recognizing self-epitopes presented on Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) complex. The majority autoantigens to in various are not known, which has impeded autoantigen identification. Recent advances immunopeptidomics have started unravel the repertoire antigenic epitopes MHC. In diseases, led identification novel and enhanced our understanding mechanisms behind autoimmunity. Especially, provided key evidence explain genetic risk posed HLA alleles. this review, we shed light how can be leveraged discover potential autoantigens. We highlight application Type 1 Diabetes (T1D), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA). Finally, practical considerations implementing successfully technical challenges that need addressed. Overall, review will provide an important context for using

Language: Английский

Citations

0
Deep Learning Enhances Precision of Citrullination Identification in Human and Plant Tissue Proteomes DOI Creative Commons
Wassim Gabriel,

Roxana González,

Sophia Laposchan

et al.

Molecular & Cellular Proteomics, Journal Year: 2025, Volume and Issue: unknown, P. 100924 - 100924

Published: Feb. 1, 2025

Language: Английский

Citations

0
Maximizing Immunopeptidomics-Based Bacterial Epitope Discovery by Multiple Search Engines and Rescoring DOI Creative Commons
Patrick J. Willems, Fabien Théry, Laura Van Moortel

et al.

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Mass spectrometry-based discovery of bacterial immunopeptides presented by infected cells allows untargeted antigens that can serve as vaccine candidates. However, reliable identification epitopes is challenged their extremely low abundance. Here, we describe an optimized bioinformatic framework to enhance the confident immunopeptides. Immunopeptidomics data cell cultures with Listeria monocytogenes were searched four different search engines, PEAKS, Comet, Sage and MSFragger, followed data-driven rescoring MS2Rescore. Compared individual engine results, this integrated workflow boosted immunopeptide average 27% led high-confidence detection 18 additional peptides (+27%) matching 15 proteins (+36%). Despite strong agreement between a small number spectra (<1%) had ambiguous matches multiple excluded ensure identifications. Finally, demonstrate our sensitive timsTOF SCP acquisition find rescoring, now inclusion ion mobility features, identifies 76% more compared Q Exactive HF acquisition. Together, results how integration along maximizes identification, boosting for development.

Language: Английский

Citations

0
Antimicrobial peptides in nematode secretions – Unveiling biotechnological opportunities for therapeutics and beyond DOI Creative Commons

E I Sutcliffe,

Allister Irvine, James Rooney

et al.

Biotechnology Advances, Journal Year: 2025, Volume and Issue: unknown, P. 108572 - 108572

Published: March 1, 2025

Language: Английский

Citations

0
Cell Storage Conditions Impact Single-Cell Proteomic Landscapes DOI Creative Commons
Bora Onat, Amanda Momenzadeh,

Ali Haghani

et al.

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Single cell transcriptomics (SCT) has revolutionized our understanding of cellular heterogeneity, yet the emergence single proteomics (SCP) promises a more functional view dynamics. A challenge is that not all mass spectrometry facilities can perform SCP, and laboratories have access to sorting equipment required for which together motivate an interest in sending bulk samples through mail SCP analysis. Shipping requires storage, unknown effect on results. This study investigates impact storage conditions proteomic landscape at level, utilizing Data-Independent Acquisition (DIA) coupled with Parallel Accumulation Serial Fragmentation (diaPASEF). Three were compared 293T cells: (1) 37 °C (control), (2) 4 overnight, (3) −196 followed by liquid nitrogen preservation. Both cold frozen induced significant alterations diameter, elongation, proteome composition. By elucidating how alter morphology profiles, this contributes foundational technical information about sample preparation data quality.

Language: Английский

Citations

0
Rustims: An Open-Source Framework for Rapid Development and Processing of timsTOF Data-Dependent Acquisition Data DOI Creative Commons
David Teschner, David Gomez‐Zepeda, Mateusz Krzysztof Łącki

et al.

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Mass spectrometry is essential for analyzing and quantifying biological samples. The timsTOF platform a prominent commercial tool this purpose, particularly in bottom-up acquisition scenarios. additional ion mobility dimension requires more complex data processing, yet most current software solutions raw are proprietary or closed-source, limiting integration into custom workflows. We introduce rustims, framework implementing flexible toolbox designed processing data, currently focusing on data-dependent (DDA-PASEF). employs dual-language approach, combining efficient, multithreaded Rust code with an easy-to-use Python interface. This allows implementations that fast, intuitive, easy to integrate. With imspy as its main scripting interface sagepy Sage search engine bindings, rustims enables integrable, intuitive processing. demonstrate capabilities pipeline DDA-PASEF including rescoring of third-party tools like the Prosit intensity predictor extended model. supports tryptic proteomics nontryptic immunopeptidomics benchmark comparisons FragPipe PEAKS. Rustims available GitHub under MIT license, installation packages multiple platforms PyPi all analysis scripts accessible via Zenodo.

Language: Английский

Citations

0
Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools – Chances and Limitations. A Critical Review DOI Open Access
Joachim Müller, Ghalia Boubaker,

Norbert Müller

et al.

Published: May 31, 2024

Identification of drug targets and biochemical investigations on mechanisms action is a are major issues in modern development. The present article reviews the classical &ldquo;one drug&rdquo; &ndash; target&rdquo; paradigm. Novel methods for target deconvolution investigation resistant strains based protein mass spectrometry have shown that multiple gene products adapta-tion involved responses pathogens to xenobiotics. This review focused protozoan pathogens. conclusions can, however, be extended chemotherapies against other or cancer. For this we searched Pubmed (pubmed.ncbi.nlm.nih.gov) Web Science (webofscience.com) using key words listed below (status May 2024)

Language: Английский

Citations

2