Article
Oncology
Leena Liljedahl, Johan Malmstrom, Bjorg Kristjansdottir, Sofia Waldemarson, Karin Sundfeldt
Summary: Ovarian cancer is a lethal disease often discovered late. A targeted assay has shown success in identifying different subtypes of ovarian cancer, potentially leading to improved early diagnostics and survival rates.
Article
Multidisciplinary Sciences
Saicharan Ghantasala, Medha Gayathri J. Pai, Sanjeeva Srivastava
Summary: Proteomic analysis of human brain tissue has improved our understanding of the brain, but brain-related disorders remain a major global cause of death. Traditional antibody-based techniques and shotgun mass spectrometry approaches have limitations in providing conclusive evidence to support hypotheses, highlighting the importance of targeted proteomics methods.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Biochemical Research Methods
Lilian R. Heil, Philip M. Remes, Michael J. MacCoss
Summary: PRM is a popular alternative to SRM for targeted proteomics, monitoring all product ions in a single spectrum. High-resolution data is not necessary to obtain high-quality quantitative data. Both mass analyzers, Orbitrap and linear ion trap, show similar technical precision but the linear ion trap has superior sensitivity and lower limits of quantitation for over 62% of peptides.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Oncology
Saicharan Ghantasala, Medha Gayathri J. Pai, Deeptarup Biswas, Nikita Gahoi, Shuvolina Mukherjee, K. P. Manubhai, Mehar Un Nissa, Alisha Srivastava, Sridhar Epari, Prakash Shetty, Aliasgar Moiyadi, Sanjeeva Srivastava
Summary: Proteomics technologies, including Multiple reaction monitoring, show promise in quantifying proteins in brain cancers, potentially offering alternative strategies with increased accuracy and sensitivity for classifying and grading tumors. Future studies involving a large cohort of samples could lead to a panel of proteins showing ability to accurately detect and quantify peptides with roles in brain malignancies, ultimately making them translatable to clinical settings.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemical Research Methods
Jakob Woessmann, David Kotol, Andreas Hober, Mathias Uhlen, Fredrik Edfors
Summary: Using multiple proteases and recombinant protein standards, this study investigates the effect of protease bias on accuracy and precision in label-free mass spectrometry experiments. The researchers successfully established quantification methods for multiple proteins.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Immunology
Ying Zhou, Shougang Kuai, Ruilin Pan, Qingqing Li, Jian Zhang, Xiaohong Gu, Huali Ren, Yubao Cui
Summary: This study aimed to investigate the plasma protein profiles of children with asthma and identify potential biomarkers. They found 347 proteins with differential expression between asthma patients and healthy children, suggesting that some of these proteins could serve as biomarkers for asthma. Further analysis revealed that these differentially expressed proteins were associated with immune response, the extracellular region, and protein binding.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Plant Sciences
Andres V. Reyes, Ruben Shrestha, Peter R. Baker, Robert J. Chalkley, Shou-Ling Xu
Summary: Accurate relative quantification is crucial in proteomic studies. Incorporating stable isotope N-15 to plant-expressed proteins in vivo is a powerful tool for accurate quantification, but it faces challenges such as incomplete labeling and contamination. This study demonstrates the use of parallel reaction monitoring (PRM) on a high-resolution mass spectrometer to achieve reliable quantification, even for low abundance proteins.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Esen Efeoglu, Michael Henry, Martin Clynes, Paula Meleady
Summary: The development of drug resistance in lung cancer is a significant clinical challenge. This study explores novel biomarkers of drug resistance in lung cancer cells and identifies the roles of ABC transporter proteins and lipid metabolism in drug resistance formation.
Article
Biochemical Research Methods
Ai Nguyen, Tingting Wang, Illarion Turko
Summary: Absolute quantification with mass spectrometry and isotope labeled internal standards has been utilized to develop and evaluate a new affinity-based approach to isolate extracellular vesicles (EVs) from human plasma. Peptides with affinity to EVs selected from phage library screening have been demonstrated as valuable ligands for EVs isolation, showing potential for drug delivery with no off-target side effects. Quantification of EVs proteins through MRM can also assist in identifying subpopulation specific markers for target-specific isolation.
JOURNAL OF PROTEOMICS
(2021)
Article
Biochemical Research Methods
Dongyoon Shin, Sang Jin Rhee, Jihyeon Lee, Injoon Yeo, Misol Do, Eun-Jeong Joo, Hee Yeon Jung, Sungwon Roh, Sang-Hyuk Lee, Hyeyoung Kim, Minji Bang, Kyu Young Lee, Jun Soo Kwon, Kyooseob Ha, Yong Min Ahn, Youngsoo Kim
Summary: This study successfully differentiated major depressive disorder (MDD) from bipolar disorder (BD) using a targeted proteomic approach, developing a model composed of nine proteins with good discriminative ability. The proteins identified were associated with neuro, oxidative/nitrosative stress, and immunity/inflammation-related biological functions.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Meizhu Zheng, Mi Zhou, Tingting Lu, Yao Lu, Peng Qin, Chunming Liu
Summary: The natural isoflavone Iristectorin B showed anti-stroke activity by reducing PC12 cell damage caused by oxygen glucose deprivation/reoxygenation and regulating ferroptosis. SLC3A2, TFR1, and HMOX1 were identified as potential diagnostic biomarkers for stroke.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Gennifer E. Merrihew, Jea Park, Deanna Plubell, Brian C. Searle, C. Dirk Keene, Eric B. Larson, Randall Bateman, Richard J. Perrin, Jasmeer P. Chhatwal, Martin R. Farlow, Catriona A. McLean, Bernardino Ghetti, Kathy L. Newell, Matthew P. Frosch, Thomas J. Montine, Michael J. MacCoss
Summary: Alzheimer's disease (AD) is a complex and devastating neurodegenerative disease with limited treatment options. In order to understand the molecular changes specific to AD, researchers have constructed a unique human brain sample cohort that includes different types of AD and normal individuals. By using advanced proteomics techniques, they have generated a high-quality dataset at the peptide and protein level, providing valuable insights into the molecular signatures of the disease. The data have been deposited in a public database and are readily accessible for further analysis.
Article
Biochemical Research Methods
Huan Wang, Peixin Jiao, Xinxin Zhang, Houjuan Xing
Summary: This study conducted proteomic analysis on the trachea of fattening pigs exposed to ammonia, identifying 126 differentially abundant proteins related to immune response, metabolism, and protein synthesis. Results were validated by IHC and PRM, providing new insight into the mechanism of NH3-induced tracheal injury.
JOURNAL OF PROTEOMICS
(2021)
Review
Microbiology
Anna Maurizio, Antonio Frangipane di Regalbono, Rudi Cassini
Summary: The study reviewed international literature on quantitative monitoring of parasites in domestic ruminants and found a wide range of information for gastrointestinal nematodes (GIN), limited data for coccidia, and no specific indications for tapeworms. For parasites like liver flukes, bronchopulmonary nematodes (BPN), and ectoparasites, the diagnostic process mainly focuses on parasite detection rather than burden estimation. Research gaps were identified, particularly in the standardization of quantitative approaches for certain parasites and the need for further investigation into the usefulness of monitoring guidelines.
Article
Biochemical Research Methods
Claudia Gaither, Robert Popp, Sophia P. Borchers, Kjartan Skarphedinsson, Finnur F. Eiriksson, Margret Thorsteinsdottir, Yassene Mohammed, Christoph H. Borchers
Summary: The study demonstrated that leaving a lyophilized peptide mixture at room temperature for up to 20 days does not affect the quantitative performance of mass spectrometry analysis, making it a feasible option for sample transportation. Most peptide concentrations showed minimal fluctuations across different time points, indicating the stability of the peptide mixture under the tested conditions.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Amy E. Campbell, Catarina Ferraz Franco, Ling- Su, Emma K. Corbin, Simon Perkins, Anton Kalyuzhnyy, Andrew R. Jones, Philip J. Brownridge, Neil D. Perkins, Claire E. Eyers
Summary: Different types of DNA damage can lead to specific pro- or anti-apoptotic cellular responses through phosphorylation-mediated signalling cascades, with NF-kappa B transcription factor RelA playing a central role. The study used label-free quantitative phosphoproteomics to investigate the effects of exposure to etoposide (ETO) or hydroxyurea (HU) on U2OS cells, and found that ETO invoked more rapid, sustained responses primarily involved in transcription, cell division and canonical DSB repair, whereas HU induced replicative stress with temporally dynamic regulation mainly related to rRNA/mRNA processing and translational initiation.
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Leonard A. Daly, Philip J. Brownridge, Michael Batie, Sonia Rocha, Violaine See, Claire E. Eyers
Summary: Cellular adaptation to low-oxygen environments is partially mediated by hypoxia-inducible factors (HIFs), whose stability and activity are regulated by post-translational modifications (PTMs) and protein-protein interactions. Hypoxia alters the complexity and composition of HIF alpha protein interaction networks, particularly for HIF-2 alpha, with the networks enriched for mitochondrial proteins. Additionally, both HIF alpha isoforms undergo heavy covalent modifications, with a majority of newly identified PTMs exhibiting oxygen dependency.
Article
Biochemical Research Methods
Lauren J. Tomlinson, Matthew Batchelor, Joscelyn Sarsby, Dominic P. Byrne, Philip J. Brownridge, Richard Bayliss, Patrick A. Eyers, Claire E. Eyers
Summary: Protein kinase inhibitors are effective in treating diseases driven by aberrant kinase signaling and can help understand the cellular roles of kinase signaling complexes. This study characterizes the conformational changes and stability of protein kinase Aurora A (Aur A) caused by binding of the physiological activator TPX2 or small molecule inhibitors using gas-phase ion-mobility mass spectrometry (IM-MS). The results show that inhibitor binding induces more compact configurations of Aur A, leading to the stabilization of active Aur A.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Biochemical Research Methods
Anton Kalyuzhnyy, Patrick A. Eyers, Claire E. Eyers, Emily Bowler-Barnett, Maria J. Martin, Zhi Sun, Eric W. Deutsch, Andrew R. Jones
Summary: This study profiles the human phosphoproteome to estimate the false discovery rate of phosphosites and predict a more realistic count of true identifications. It highlights significant potential of false-positive data in phosphorylation databases and emphasizes the importance of quality control for such data.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Multidisciplinary Sciences
Laura Marr, Dipsikha Biswas, Leonard A. Daly, Christopher Browning, Sarah C. M. Vial, Daniel P. Maskell, Catherine Hudson, Jay A. Bertrand, John Pollard, Neil A. Ranson, Heena Khatter, Claire E. Eyers, Kei Sakamoto, Elton Zeqiraj
Summary: The study describes the structural basis of glycogen synthase (GS) regulation, specifically its inactivation mechanism through phosphorylation. The findings provide insights into glycogen synthesis regulation and facilitate research on glycogen-related diseases.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Mitchell H. Omar, Dominic P. Byrne, Kiana N. Jones, Tyler M. Lakey, Kerrie B. Collins, Kyung-Soon Lee, Leonard A. Daly, Katherine A. Forbush, Ho-Tak Lau, Martin Golkowski, G. Stanley McKnight, David T. Breault, Anne-Marie Lefrancois-Martinez, Antoine Martinez, Claire E. Eyers, Geoffrey S. Baird, Shao-En Ong, F. Donelson Smith, Patrick A. Eyers, John D. Scott
Summary: Mutations in protein kinase A catalytic subunit lead to adrenal Cushing's syndrome, and the mutants are excluded from kinase-anchoring protein signaling islands, resulting in excessive cortisol production. Incorporating the mutants into kinase-anchoring protein complexes restores normal endocrine function. Each mutant activates a different signaling pathway, contributing to the development of the disease.
Article
Biochemistry & Molecular Biology
Jill E. Hunter, Amy E. Campbell, Scott Kerridge, Callum Fraser, Nicola L. Hannaway, Saimir Luli, Iglika Ivanova, Philip J. Brownridge, Jonathan Coxhead, Leigh Taylor, Peter Leary, Megan S. R. Hasoon, Claire E. Eyers, Neil D. Perkins
Summary: In this study, we discovered the up-regulation of multiple bypass pathways in lymphomas with mutant NF-kappa B subunits, and demonstrated that drugs targeting these pathways could potentially be used to aid the successful clinical application of CHK1 inhibitors.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Jill E. Hunter, Amy E. Campbell, Jacqueline A. Butterworth, Helene Sellier, Nicola L. Hannaway, Saimir Luli, Achilleas Floudas, Niall S. Kenneth, Adam J. Moore, Philip J. Brownridge, Huw D. Thomas, Jonathan Coxhead, Leigh Taylor, Peter Leary, Megan S. R. Hasoon, Andrew M. Knight, Michelle D. Garrett, Ian Collins, Claire E. Eyers, Neil D. Perkins
Summary: DNA replication stress is a common feature of cancer cells, and ATR/CHK1 signaling pathway is an attractive target for anti-cancer therapies. This study reveals the critical role of RelA NF-xB subunit in MYC induced DNA replication stress, suggesting its potential as a therapeutic target.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Jill E. Hunter, Amy E. Campbell, Nicola L. Hannaway, Scott Kerridge, Saimir Luli, Jacqueline A. Butterworth, Helene Sellier, Reshmi Mukherjee, Nikita Dhillon, Praveen D. Sudhindar, Ruchi Shukla, Philip J. Brownridge, Hayden L. Bell, Jonathan Coxhead, Leigh Taylor, Peter Leary, Megan S. R. Hasoon, Ian Collins, Michelle D. Garrett, Claire E. Eyers, Neil D. Perkins
Summary: The study found that deleting c-Rel results in earlier onset of lymphoma, contrary to the expected function of this NF-xB subunit. E mu-Myc/cRel-/- lymphomas were shown to have a major defect in the CHK1 pathway, involving a loss of CHK1 protein expression and resistance to CHK1 inhibitor treatment.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Dominic P. Byrne, Safal Shrestha, Leonard A. Daly, Vanessa Marensi, Krithika Ramakrishnan, Claire E. Eyers, Natarajan Kannan, Patrick A. Eyers
Summary: Pseudokinases lack conserved amino acids for catalytic activity and have diverse biological functions. Human PSKH2 is a pseudokinase closely related to the canonical kinase PSKH1. Species-level adaptations have led to the appearance of PSKH2 variants alongside PSKH1 in vertebrate genomes. PSKH2 lacks protein phosphotransferase activity and its N-terminal domain is required for stable expression and localization to the mitochondrial fraction. PSKH2 is part of a mitochondrial protein network and its expression is regulated through the HSP90/Cdc37 chaperone system.
BIOCHEMICAL JOURNAL
(2023)
Editorial Material
Biochemical Research Methods
John R. Yates, Ileana M. Cristea, Meng-Qui Dong, Claire E. Eyers, Joshua LaBaer, Jia V. Li, Jeremy K. Nicholson, Christopher M. Overall, Magnus Palmblad, Nikolai Slavov
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Biochemical Research Methods
Leandro Xavier Neves, R. Alan Wilson, Philip Brownridge, Stephen W. W. Holman, Victoria M. M. Harman, Claire E. E. Eyers, Robert J. J. Beynon, William Castro-Borges
Summary: In this study, a detailed method for preserving the proteome of adult Schistosoma mansoni worms was described in order to enrich the tissues associated with the parasite's alimentary tract. The methodology employed label-free and QconCAT-based absolute quantification to detect S. mansoni oesophageal gland products. By stabilizing the proteome and minimizing sample degradation during dissection, the hidden proteome of target tissues, which are not readily available from total lysates due to their small volumes, could be accessed. This protocol can be used for the discovery of proteins with potential diagnostic and therapeutic utility in other Schistosoma species lacking quantitative proteomics characterization of specialized tissues.
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
(2023)
Article
Biochemical Research Methods
Leonard A. Daly, Dominic P. Byrne, Simon Perkins, Philip J. Brownridge, Euan Mcdonnell, Andrew R. Jones, Patrick A. Eyers, Claire E. Eyers
Summary: In this study, a MS-based workflow for sY-peptide characterization was developed, allowing systematic investigation of the sulfome. The key for distinguishing sulfated peptides from phosphopeptides was low collision energy-induced neutral loss. Applying this workflow identified 21 new sulfotyrosine-containing proteins and revealed new interplay between enzymes relevant to both protein and glycan sulfation.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemical Research Methods
Allen Po, Claire Eyers
Summary: Top-down proteomics aims to identify and analyze intact proteoforms extracted from biological samples. However, defining and pinpointing post-translational modifications on intact proteins remains a challenge. This is crucial for understanding the specific roles and structure-function relationships of proteins.
JOURNAL OF PROTEOME RESEARCH
(2023)
Review
Chemistry, Multidisciplinary
Leonard A. Daly, Christopher J. Clarke, Allen Po, Sally O. Oswald, Claire E. Eyers
Summary: The article focuses on the application of mass spectrometry in the identification and quantification of protein modifications, specifically phosphorylation and sulfation. It discusses the challenges associated with discriminating and pinpointing the sites of these modifications on polypeptide chains. The article showcases various approaches for enrichment and site localisation of phosphorylated and sulfated peptides, as well as modification analysis in intact proteins. It also discusses the use of native ion-mobility MS to explore the effects of these modifications on protein structure and ligand binding. The article provides insights into the current strategies and future directions in studying phosphorylation and sulfation using mass spectrometry.
CHEMICAL COMMUNICATIONS
(2023)
