Article
Chemistry, Multidisciplinary
Kaitlin Schaefer, Irene Lui, James R. Byrnes, Emily Kang, Jie Zhou, Amy M. Weeks, James A. Wells
Summary: Proteolytic cleavage of cell surface proteins plays a crucial role in processes such as cell-cell interactions, receptor activation, and shedding of signaling proteins. This study introduces a proteomic approach called cell surface N-terminomics, which allows for the identification of precise cleavage sites on living cells. By utilizing a peptide ligase called stabiligase, extracellular neo-N-termini can be efficiently tagged for proteomic analysis. The study demonstrates the versatility of this approach by identifying and characterizing numerous extracellular neo-N-termini in different cell types, including primary immune cells. The findings also reveal the involvement of single oncogenes, KRAS(G12V) and HER2, in the proteolytic remodeling of proteins associated with cancerous cell growth, invasion, and migration. Cell surface N-terminomics provides a generalizable platform for targeting proteolyzed epitopes using immunotherapies.
ACS CENTRAL SCIENCE
(2022)
Article
Chemistry, Analytical
Jinghan Yang, Zhiqiang Gao, Xiuhan Ren, Jie Sheng, Ping Xu, Cheng Chang, Yan Fu
Summary: Proteolytic digestion of proteins is crucial in shotgun proteomics for further analysis, but the completion of digestion is often hindered by missed cleavage sites. DeepDigest, a deep learning algorithm, accurately predicts cleavage sites of various proteases, outperforming traditional machine learning algorithms. Transfer learning further enhances prediction accuracy and reveals interesting characteristics of different proteases.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Sriram Gummadi, Taeyoung Kang, Pamali Fonseka, Sai Chitti, Ching-Seng Ang, Suresh Mathivanan
Summary: In this study, a user-friendly standalone tool called Pep2Graph was developed to integrate and analyze in-gel proteomics data, facilitating the study of proteolytic events in normal physiology and pathology.
Article
Oncology
Xia Chen, Qianwen Zheng, Li Ji, Yanyan Zhuang, Hao Yu, Xinmeng Cheng, Yun Han, Jinxing Lv, Bo Zheng, Yanli Zheng, Jun Yu
Summary: This study identified molecular signaling pathways related to missed abortion (MA) using a quantitative proteomics approach. They found that COX6C played a critical role in MA and its down-regulated expression may contribute to the pathophysiology of MA. The study helps to understand the pathophysiological mechanisms of MA.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Yulia V. Samukhina, Dmitriy D. Matyushin, Oksana I. Grinevich, Aleksey K. Buryak
Summary: The study utilizes deep learning techniques to predict peptide collision cross-section values more accurately compared to previous methods, using a complex structure of convolutional neural networks. By integrating additional information such as chromatographic retention time and ion mobility spectrum, the accuracy of analysis has been significantly improved.
Article
Biochemistry & Molecular Biology
Chun-Yao Yang, Simone Bonelli, Matteo Calligaris, Anna Paola Carreca, Stephan A. Mueller, Stefan F. Lichtenthaler, Linda Troeberg, Simone D. Scilabra
Summary: ADAM15, a member of the ADAM family, plays an important role in various biological functions, particularly in cartilage homeostasis. Proteomic analysis of HTB94 cells manipulated to have altered ADAM15 expression levels showed that ADAM15 can modulate the secretome independent of its catalytic activity, notably increasing levels of TIMP-3. This suggests a novel mechanism by which ADAM15 exerts its biological functions beyond canonical substrate cleavage.
Article
Chemistry, Analytical
Jinyi Wu, Shuyi Huang, Lei Tan, Yuling Li, Xiaotong Wu, Yong Liang
Summary: The study suggests an alternative strategy for detecting dengue virus NS1 antigen in clinical serum samples using UHPLC-MS/MS and molecularly imprinted polymers, showing significant promise for early confirmation of infection.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shuai Zeng, Ziting Mao, Yijie Ren, Duolin Wang, Dong Xu, Trupti Joshi
Summary: G2PDeep is an open-access web server that provides a deep-learning framework for quantitative phenotype prediction and genomic marker discovery. It allows researchers to create and train models through an interactive web interface, monitor training process, and compare model performance. Additionally, G2PDeep integrates multiple datasets, including the soybean nested association mapping data, for predictions of quantitative phenotypes and genomic markers.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Analytical
Tarang Jadav, Pinaki Sengupta
Summary: In this study, an Excel-based ProteoExcel(TP) tool was developed for the quick and accurate selection of surrogate peptides for the entire protein family. The tool is highly user-friendly and flexible, which can significantly reduce the workload and increase efficiency for scientists working in proteomics research.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Multidisciplinary Sciences
Saeed Ahmad, Phasit Charoenkwan, Julian M. W. Quinn, Mohammad Ali Moni, Md Mehedi Hasan, Pietro Lio, Watshara Shoombuatong
Summary: In this study, a computational approach called SCORPION is proposed for the accurate identification of phage virion proteins (PVPs) using only protein primary sequences. By exploring various feature descriptors and machine learning algorithms, optimal baseline models were constructed and a two-step feature selection strategy was used to determine the optimal feature vector. Results demonstrate that SCORPION outperforms existing methods and shows superior predictive performance.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Chemistry, Multidisciplinary
Marco Cavaco, David Andreu, Miguel A. R. B. Castanho
Summary: Proteolytic stability assessment is seen as a crucial aspect of peptide characterization, with challenges in comparing data due to varying assay methods and reporting styles. Guidelines for better communication among experts are suggested for improved data readability and utilization of peptide stability information.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Analytical
John G. Pavek, Brian L. Frey, Dustin C. Frost, Ting-Jia Gu, Lingjun Li, Lloyd M. Smith
Summary: Top-down proteomics is a method for characterizing intact proteoforms in complex mixtures, but it may compromise the depth of proteoform coverage on liquid chromatography time scales. We propose a strategy that combines intact mass determination with cysteine count to identify proteoforms in tissue samples.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Zhongjie Wang, Lei Zhang, Wenjuan Yuan, Ying Zhang, Haojie Lu
Summary: The SAPT workflow based on SCX fractionation allows simultaneous analysis of protein N- and C-termini, resulting in the identification of a large number of new termini in a cell line.
ANALYTICAL CHEMISTRY
(2021)
Review
Biology
Jaana Kunnapuu, Honey Bokharaie, Michael Jeltsch
Summary: VEGFs play crucial roles in regulating blood and lymphatic vessel growth, with potential therapeutic implications for diseases like cancer and heart disease. Enzymatic activation of VEGF-C and VEGF-D by specific proteases is a critical step in their functional regulation. Understanding the molecular mechanisms behind these processes is essential for developing successful therapies targeting VEGF-C and VEGF-D in lymphatic-related diseases.
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
Multidisciplinary Sciences
David Talavera, Christopher J. Kershaw, Joseph L. Costello, Lydia M. Castelli, William Rowe, Paul F. G. Sims, Mark P. Ashe, Chris M. Grant, Graham D. Pavitt, Simon J. Hubbard
SCIENTIFIC REPORTS
(2018)
Article
Biochemistry & Molecular Biology
Roza Szatkowska, Manuel Garcia-Albornoz, Katarzyna Roszkowska, Stephen W. Holman, Emil Furmanek, Simon J. Hubbard, Robert J. Beynon, Malgorzata Adamczyk
BIOCHEMICAL JOURNAL
(2019)
Article
Biochemistry & Molecular Biology
Katherine A. Wood, Charlie F. Rowlands, Wasay Mohiuddin Shaikh Qureshi, Huw B. Thomas, Weronika A. Buczek, Tracy A. Briggs, Simon J. Hubbard, Kathryn E. Hentges, William G. Newman, Raymond T. O'Keefe
HUMAN MOLECULAR GENETICS
(2019)
Article
Engineering, Chemical
Chuan Fu Yap, Manuel Garcia-Albornoz, Andrew F. Jarnuczak, Simon J. Hubbard, Jean-Marc Schwartz
Summary: Research has shown that under heat stress conditions, Saccharomyces cerevisiae increases trehalose production and glycolytic flux, with pyruvate kinase playing a key role in the increase in metabolic flux. The increase in trehalose metabolic pathway flux is primarily due to regulatory effects, and overexpression of enzymes involved in trehalose metabolism can lead to higher trehalose yield in the cell.
Article
Multidisciplinary Sciences
Fabian Morales-Polanco, Christian Bates, Jennifer Lui, Joseph Casson, Clara A. Solari, Mariavittoria Pizzinga, Gabriela Forte, Claire Griffin, Kirsten E. L. Garner, Harriet E. Burt, Hannah L. Dixon, Simon Hubbard, Paula Portela, Mark P. Ashe
Summary: Studies have shown that glycolytic mRNAs are localized to granules for active translation, which is critical for their localization and likely facilitates higher level organization and control of the glycolytic pathway. These granules, termed core fermentation (CoFe) granules, seem to function as translation factories for high-level coordinated enzyme synthesis necessary for a critical metabolic pathway.
Article
Genetics & Heredity
Charlie F. Rowlands, Algy Taylor, Gillian Rice, Nicola Whiffin, Hildegard Nikki Hall, William G. Newman, Graeme C. M. Black, Raymond T. O'Keefe, Simon Hubbard, Andrew G. L. Douglas, Diana Baralle, Tracy A. Briggs, Jamie M. Ellingford
Summary: Variable gene expression levels between tissues complicate the use of RNA sequencing for delineating genomic variants impact. A gene and tissue-specific metric, MRSD, overcomes limitations of using expression values alone, estimating the required sequencing depth to achieve desired coverage. Fibroblasts are identified as the optimal RNA source using MRSD, demonstrating its utility in functional assessment of splicing aberrations, particularly in Mendelian genetic disorders context.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Christopher J. Kershaw, Michael G. Nelson, Jennifer Lui, Christian P. Bates, Martin D. Jennings, Simon J. Hubbard, Mark P. Ashe, Chris M. Grant
Summary: This study systematically determined the protein and mRNA composition of P-bodies and stress granules before and after nutrient stress, revealing the existence of high molecular weight complexes as potential seeds for mature condensates. Shared proteins and RNA components between these biological condensates were identified, highlighting a complex interaction profile during their maturation process. The interaction networks represent a tunable response to stress, showcasing previously unrecognized condensate heterogeneity.
Article
Biology
Robert A. Crawford, Mark P. Ashe, Simon J. Hubbard, Graham D. Pavitt
Summary: Translation regulation is an important cellular response to changing external conditions. This study identified RNA-binding proteins (RBPs) involved in translational control using polysome profiling and mass spectrometry. The results revealed previously under-appreciated RBPs and their roles in response to oxidative stress and amino acid starvation.
Article
Multidisciplinary Sciences
Mathias Walzer, David Garcia-Seisdedos, Ananth Prakash, Paul Brack, Peter Crowther, Robert L. Graham, Nancy George, Suhaib Mohammed, Pablo Moreno, Irene Papatheodorou, Simon J. Hubbard, Juan Antonio Vizcaino
Summary: This study introduces a re-analysis pipeline for public SWATH-MS datasets, which includes automated workflows and statistical analysis, and integrates the results into the Expression Atlas resource. By reanalysing 10 public DIA datasets, the robustness of the pipeline was validated, and the final results were integrated into Expression Atlas.
Review
Biochemistry & Molecular Biology
Declan R. Creamer, Simon J. Hubbard, Mark P. Ashe, Chris M. Grant
Summary: Eukaryotic cells have developed a complex circuitry of signalling molecules to monitor changes in their environments. The cAMP/PKA pathway is an important glucose sensing circuit in yeast, and PKA activity regulates various processes in yeast growth. However, the molecular basis of PKA signalling specificity is poorly understood.
Article
Biochemistry & Molecular Biology
Kwan Ting Kan, Michael G. Nelson, Chris M. Grant, Simon J. Hubbard, Hui Lu
Summary: Yme1 is a multifunctional protein that plays important roles in maintaining mitochondrial protein homeostasis and regulating biogenesis and function of mitochondrial proteins. This study shows that YME1 deletion affects yeast growth, chronological life span, mitochondrial protein homeostasis and function. It also reveals that Yme1 plays a key role in longevity and is important for maintaining the level and function of mitochondrial oxidative phosphorylation complexes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Martin Rusilowicz, David W. Newman, Declan R. Creamer, James Johnson, Kareena Adair, Victoria M. Harman, Chris M. Grant, Robert J. Beynon, Simon J. Hubbard
Summary: Protein quantitation via mass spectrometry requires the use of peptide proxies, and accurate quantitation often relies on the addition of an external standard. AlacatDesigner is a tool that assists in selecting suitable peptide candidates for recombinant protein standards. It considers factors such as target protein, existing databases, literature occurrence, potential post-translational modifications, and ionization potential within the mass spectrometer.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Jack Llewellyn, Venkatesh Mallikarjun, Ellen Appleton, Maria Osipova, Hamish T. J. Gilbert, Stephen M. Richardson, Simon J. Hubbard, Joe Swift
Summary: Cells respond to stress by producing chaperone proteins to maintain protein function, but aging leads to a disruption of protein balance and the formation of disease-related protein aggregates. Understanding the molecular causes of this proteostasis deterioration is important for disease interventions and cell health maintenance in regenerative medicine strategies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
M. Garcia-Albornoz, S. W. Holman, T. Antonisse, P. Daran-Lapujade, B. Teusink, R. J. Beynon, S. J. Hubbard
Article
Biochemistry & Molecular Biology
Andrew F. Jarnuczak, Manuel Garcia Albornoz, Claire E. Eyers, Christopher M. Grant, Simon J. Hubbard