Article
Biochemistry & Molecular Biology
Van-An Duong, Onyou Nam, EonSeon Jin, Jong-Moon Park, Hookeun Lee
Summary: Emiliania huxleyi, a cosmopolitan coccolithophore, was studied for the global discovery of post-translational modifications (PTMs) using a three-dimensional separation method combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methylation was found to be the most frequent PTM, with lysine being the most frequently modified amino acid. The number of identified proteins increased by 22.5% after the PTM search, with some proteins showing a significant increase in intensity.
Article
Multidisciplinary Sciences
Nathalie Kyalu Ngoie Zola, Clemence Balty, Sebastien Pyr dit Ruys, Axelle A. T. Vanparys, Nicolas D. G. Huyghe, Gaetan Herinckx, Manuel Johanns, Emilien Boyer, Pascal Kienlen-Campard, Mark H. Rider, Didier Vertommen, Bernard J. Hanseeuw
Summary: Tau isoforms in insoluble aggregates differ between tauopathies, but not in soluble brain extracts. This study characterizes the post-translational modifications of aggregated and soluble tau protein in various tauopathies, revealing specific soluble signatures for each tauopathy.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Gengjun Zhu, Lifang Jin, Wanchun Sun, Shuang Wang, Ning Liu
Summary: This review highlights the importance of post-translational modifications (PTMs) in colorectal cancer (CRC) and discusses their role in diagnosis, prognosis, and treatment. The review summarizes the proteomic profiling strategies for key PTMs and describes the methods used to delineate the global landscapes of each PTM. The review also discusses the current status of PTM research in CRC and provides future perspectives on the role of PTM regulation in translational medicine for CRC.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Review
Biochemistry & Molecular Biology
Bethany C. Taylor, Nicolas L. Young
Summary: Histone post-translational modifications (PTMs) play a crucial role in regulating the genome by storing and transmitting complex signals about the genome state. Different PTM sites on the same histone molecule or nucleosome work in concert, supported by 'readers' structures, to transduce signals in specific cellular contexts.
BIOCHEMICAL JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Juliane Hermann, Leon Schurgers, Vera Jankowski
Summary: Post-translational modifications play a key role in protein function and disease progression, but their reliable detection and quantification remain a challenge in clinical diagnosis. Mass spectrometry offers a solution, but its clinical translation still faces challenges.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Assaf Kacen, Aaron Javitt, Matthias P. Kramer, David Morgenstern, Tomer Tsaban, Merav D. Shmueli, Guo Ci Teo, Felipe da Veiga Leprevost, Eilon Barnea, Fengchao Yu, Arie Admon, Lea Eisenbach, Yardena Samuels, Ora Schueler-Furman, Yishai Levin, Alexey Nesvizhskii, Yifat Merbl
Summary: This study describes an antigen discovery pipeline that analyzes different post-translational modifications (PTMs) of antigens, expands the antigen landscape, and reveals disease-specific modified targets, which have important implications for T cell-mediated therapies in cancer and other fields.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Poornima Ramesh, Santosh Kumar Behera, Chinmaya Narayana Kotimoole, Varshasnata Mohanty, Rajesh Raju, T. S. Keshava Prasad, Jalaluddin Akbar Kandel Codi
Summary: Gastric cancers are characterized by late diagnosis and poor prognosis, and protein post-translational modifications (PTMs) have been associated with cancer development and metastasis. However, limited data is available on PTMs in gastric cancers. This study used an iterative searching strategy to analyze mass spectrometry data and identified 21,710 unique modification sites on 16,364 modified peptides. The majority of the altered PTMs/proteins were found in cytoskeletal and extracellular matrix proteins, which are known to be perturbed in gastric cancer.
Review
Agriculture, Multidisciplinary
Janette Bobalova, Dana Strouhalova, Pavel Bobal
Summary: Post-translational modifications (PTMs) play a crucial role in understanding the biological complexity generated by a small number of genes. The PTMs of barley proteins, including phosphorylation, glycation, and glycosylation, are important for metabolism and regulation. Innovative analytical approaches are needed to study and characterize PTMs in more detail.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Parasitology
Sebastian Miles, Javier Magnone, Joaquin Garcia-Luna, Sylvia Dematteis, Gustavo Mourglia-Ettlin
Summary: This study provides insights into the post-translational modifications (PTMs) of proteins in E. granulosus s.l., including the identification of new PTMs and the enzymes involved. These findings expand our knowledge on PTMs in platyhelminthes.
Review
Cell Biology
Rita Azevedo, Chloe Jacquemin, Nicolas Villain, Francois Fenaille, Foudil Lamari, Francois Becher
Summary: Neurodegenerative diseases are incurable disorders that challenge modern medicine. A deeper understanding of the pathogenesis underlying these diseases is necessary to develop new diagnostic biomarkers and disease-modifying therapy. Mass spectrometry analysis has provided breakthroughs in studying post-translational modifications in neurodegenerative diseases and discovering potential clinical markers.
Article
Chemistry, Analytical
Tessa Reinert, Pascal Houze, Nathalie Mignet, Yannis-Nicolas Francois, Rabah Gahoual
Summary: Despite the challenges in predicting and monitoring post-administration effects of post-translational modifications, this study identified and evaluated the modification kinetics of infliximab and its biosimilars in vitro. The methodology used mass spectrometry analysis to determine modified and unmodified forms, and the results showed the potential for studying structural stability after administration.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Plant Sciences
Jonas Giese, Juergen Eirich, Dirk Walther, Youjun Zhang, Ines Lassowskat, Alisdair R. Fernie, Marlene Elsaesser, Veronica G. Maurino, Markus Schwarzlaender, Iris Finkemeier
Summary: The transition from dark to light in the diurnal cycle causes significant physiological changes in plant metabolism, which require specific modes of regulation. While the activities of key metabolic enzymes regulated by light-dependent post-translational modifications (PTMs) have been extensively studied at the protein level, a comprehensive understanding of the global dynamics of light-dependent PTMs is lacking. In this study, we investigated the changes in the metabolome and proteome in Arabidopsis rosettes in response to light in a time-dependent manner, focusing on phosphorylation, lysine acetylation, and cysteine-based redox switches. Our findings revealed that over 1700 out of more than 24,000 detected PTM sites were altered during the transition from dark to light, with different compartments showing distinct PTM changes at different timepoints.
Review
Biochemical Research Methods
Yi Yang, Liang Qiao
Summary: Protein post-translational modifications (PTMs) increase the functional diversity of the cellular proteome. Accurate quantification and identification of protein PTMs is crucial in proteomics research. Recent advancements in data-independent acquisition (DIA) mass spectrometry (MS) have enabled deep coverage and accurate quantification of PTMs. This review provides an overview of DIA data processing methods for PTMs analysis, as well as deep learning methods that enhance PTMs analysis. The limitations and future directions of DIA methods for PTMs analysis are also discussed.
Review
Biochemistry & Molecular Biology
Maria Gaetana Giovanna Pittala, Stefano Conti Nibali, Simona Reina, Vincenzo Cunsolo, Antonella Di Francesco, Vito De Pinto, Angela Messina, Salvatore Foti, Rosaria Saletti
Summary: VDAC (voltage-dependent anion selective channel) proteins, also known as mitochondrial porins, are crucial in cellular processes, metabolism regulation, and survival pathways due to their abundance and function as cellular hubs. Their structural characterization poses challenges due to high hydrophobicity, low solubility, and difficulty in isolation, leading to a need for analysis as components of a complex mixture. Recent advancements in tools such as nano-reversed phase ultra-high performance liquid chromatography (nanoRP-UHPLC) and ultra-sensitive high-resolution mass spectrometry (HRMS) have greatly contributed to the understanding of post-translational modifications (PTMs) of VDAC proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemical Research Methods
Jessica Brandi, Roberta Noberini, Tiziana Bonaldi, Daniela Cecconi
Summary: This review provides an overview of the most common post-translational modifications (PTMs) of proteins and discusses enrichment methods for MS-based proteomics analysis. Both traditional affinity strategies and chemical enrichment strategies are detailed, and the challenges and future trends in the field are discussed.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Biology
Tayfun Tumkaya, Safwan Burhanudin, Asghar Khalilnezhad, James Stewart, Hyungwon Choi, Adam Claridge-Chang
Summary: Animals use olfactory receptors to navigate mates, food, and danger. Research on Drosophila reveals that only a small fraction of olfactory sensory neurons can individually drive avoidance or attraction behavior, suggesting that most neurons have neutral effects. Additionally, wind and hunger have minimal impact on these responses. Comparisons between single- and double-ORN responses also contradict simple pooling rules, indicating that complex interactions may be responsible for the observed behavioral effects.
Article
Biochemistry & Molecular Biology
Shaohuan Wu, Ted M. Ross, Michael A. Carlock, Elodie Ghedin, Hyungwon Choi, Christine Vogel
Summary: The study identifies determinants of influenza vaccine efficacy, with prior vaccination history, baseline titer level, and age being major factors. Other factors such as BMI, comorbidities, vaccine dose, and race have negligible effects. Models can accurately predict categorical responses in most cases, and generate a new seroconversion score corrected for these factors, facilitating future biomarker identification.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Chemistry, Analytical
Junho Park, Fengchao Yu, James M. Fulcher, Sarah M. Williams, Kristin Engbrecht, Ronald J. Moore, Geremy C. Clair, Vladislav Petyuk, Alexey I. Nesvizhskii, Ying Zhu
Summary: To overcome the issue of ratio compression in isobaric labeling-based multiplexed single-cell proteomics, we developed an improved MS3-based method using a linear ion trap. This method increased proteome coverage for single-cell-level peptides and was applied to study immune activation in single macrophages.
ANALYTICAL CHEMISTRY
(2023)
Article
Oncology
Yize Li, Tung-Shing M. Lih, Saravana M. Dhanasekaran, Rahul Mannan, Lijun Chen, Marcin Cieslik, Yige Wu, Rita Jiu-Hsien Lu, David J. Clark, Iga Koodziejczak, Runyu Hong, Siqi Chen, Yanyan Zhao, Seema Chugh, Wagma Caravan, Nataly Naser Al Deen, Noshad Hosseini, Chelsea J. Newton, Karsten Krug, Yuanwei Xu, Kyung-Cho Cho, Yingwei Hu, Yuping Zhang, Chandan Kumar-Sinha, Weiping Ma, Anna Calinawan, Matthew A. Wyczalkowski, Michael C. Wendl, Yuefan Wang, Shenghao Guo, Cissy Zhang, Anne Le, Aniket Dagar, Alex Hopkins, Hanbyul Cho, Felipe da Veiga Leprevost, Xiaojun Jing, Guo Ci Teo, Wenke Liu, Melissa A. Reimers, Russell Pachynski, Alexander J. Lazar, Arul M. Chinnaiyan, Brian A. Van Tine, Bing Zhang, Karin D. Rodland, Gad Getz, D. R. Mani, Pei Wang, Feng Chen, Galen Hostetter, Mathangi Thiagarajan, W. Marston Linehan, David Fenyo, Scott D. Jewell, Gilbert S. Omenn, Rohit Mehra, Maciej Wiznerowicz, Ana I. Robles, Mehdi Mesri, Tara Hiltke, Eunkyung An, Henry Rodriguez, Daniel W. Chan, Christopher J. Ricketts, Alexey I. Nesvizhskii, Hui Zhang, Li Ding
Summary: By integrating histopathologic, proteogenomic, and metabolomic analyses, this study reveals the inter- and intratumoral heterogeneity of clear cell renal cell carcinomas (ccRCCs). It identifies high-risk disease subsets based on tumor grade, BAP1 mutation, genome instability, hypermethylation, and protein glycosylation signature. RNA sequencing provides insights into gene signatures and potential targeted therapies, while in vitro cell line studies validate the efficacy of inhibiting identified phosphoproteome targets.
Article
Virology
Shaohuan Wu, Smruti Pushalkar, Shuvadeep Maity, Matthew Pressler, Justin Rendleman, Burcu Vitrinel, Michael Carlock, Ted Ross, Hyungwon Choi, Christine Vogel
Summary: This study analyzed serum samples from 138 influenza vaccine recipients, finding a positive correlation between cholesterol transport proteins and seroconversion, a significant association between actin cytoskeleton dynamics proteins and high adjusted seroconversion, and complex interactions of complement system proteins in different age groups.
Article
Biochemical Research Methods
Daniel A. Polasky, Daniel J. Geiszler, Fengchao Yu, Kai Li, Guo Ci Teo, Alexey I. Nesvizhskii
Summary: Posttranslational modifications of proteins play crucial roles in defining and regulating protein functions. Traditional methods for identifying these modifications using mass spectrometry-based proteomics have limitations, as they treat modifications as static attachments to peptide sequences. However, many modifications undergo fragmentation during mass spectrometry experiments, offering opportunities for improved searches. In this study, a new labile mode in the MSFragger search engine was developed to incorporate modification-specific fragment ions, resulting in significant improvements in identifying phosphopeptides, RNA-crosslinked peptides, and ADP-ribosylated peptides.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Multidisciplinary Sciences
Georges Bedran, Daniel A. Polasky, Yi Hsiao, Fengchao Yu, Felipe da Veiga Leprevost, Javier A. Alfaro, Marcin Cieslik, Alexey I. Nesvizhskii
Summary: In this study, a fast computational workflow merging the MSFragger-Glyco search algorithm with a false discovery rate control is introduced for analyzing glycopeptides from mass spectrometry-based immunopeptidome data. The authors analyze eight large-scale publicly available studies and find that glycosylated MHC-associated peptides are predominantly presented by MHC class II. They present a comprehensive resource, HLA-Glyco, which contains over 3,400 human leukocyte antigen (HLA) class II N-glycopeptides from 1,049 distinct protein glycosylation sites. This resource provides valuable insights into glycosylation properties in antigen recognition and immune modulation.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Analytical
Carolina Rojas Ramirez, Jessica A. Espino, Lisa M. Jones, Daniel A. Polasky, Alexey I. Nesvizhskii
Summary: Monitoring protein structure before and after environmental alterations can provide insights into protein function. Fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry allows for monitoring of structural rearrangements by exposing proteins to radicals. However, the challenges of processing FPOP data have limited its proteome-scale uses. In this study, a computational workflow was developed to analyze FPOP data sets more efficiently, enabling the identification of modified peptide spectra at a faster rate than previous methods.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hana Popelka, Vikramjit Lahiri, Wayne D. Hawkins, Felipe da Veiga Leprevost, Alexey I. Nesvizhskii, Daniel J. Klionsky
Summary: The intrinsically disordered protein region (IDPR) of Atg12 protein plays an important role in its functional structure, as it is positioned in proximity to the ubiquitin-like (UBL) domain. Deletion in IDPR disrupts the integrity of the UBL domain, while a mutation in the predicted α0 helix in IDPR prevents Atg12 from binding to Atg7 and Atg10, impacting its function in the ubiquitin-like conjugation cascade.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Vi T. Tang, Prabhodh S. Abbineni, Felipe da Veiga Leprevost, Venkatesha Basrur, Rami Khoriaty, Brian T. Emmer, Alexey I. Nesvizhskii, David Ginsburg
Summary: Proteins are transported to the Golgi apparatus through COPII-coated vesicles or tubules, with LMAN1 and SURF4 being important receptors in this process. LMAN1 has limited clients in HuH7 cells, while SURF4 traffics a broad range of cargoes, suggesting complex cargo recognition mechanisms.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Fengchao Yu, Guo Ci Teo, Andy T. T. Kong, Klemens Froehlich, Ginny Xiaohe Li, Vadim Demichev, Alexey I. Nesvizhskii
Summary: MSFragger-DIA is a fast and sensitive tool for direct peptide identification from DIA spectra, demonstrating excellent performance in applications such as large-scale tumor studies and single-cell proteomics.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Kevin L. Yang, Fengchao Yu, Guo Ci Teo, Kai Li, Vadim Demichev, Markus Ralser, Alexey I. Nesvizhskii
Summary: This article presents an accessible method to improve peptide spectrum match rescoring using deep learning predictions in bottom-up proteomics. The authors demonstrate significant improvements in peptide/protein identifications across various experiments, including single-cell proteomics and immunopeptidomics. They introduce a new tool called MSBooster, which incorporates deep learning-based predictions of peptide properties to rescore peptide-to-spectrum matches, and show its utility in different workflows, such as immunopeptidomics and single-cell proteomics.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Daniel J. Geiszler, Daniel A. Polasky, Fengchao Yu, Alexey I. Nesvizhskii
Summary: Post-translational modifications are important in proteomics, but can complicate searches for modified peptides. The authors present an automated method to find diagnostic spectral features for any modification, improving peptide recovery and localization. They demonstrate the utility of this approach for various modifications and analyze the interactions between ion intensity and statistical properties. This method has been incorporated into PTM-Shepherd and FragPipe.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Kristina Allgoewer, Shaohuan Wu, Hyungwon Choi, Christine Vogel
Summary: Due to the implications for pregnancy outcomes, understanding the molecular differences between Zika virus (ZIKV) and dengue virus (DENV) infections is of high interest. Through analyzing mass spectra, researchers identified 246 modified peptides with significantly differential abundance in ZIKV and DENV patients. Methionine-oxidized peptides from apolipoproteins and glycosylated peptides from immunoglobulin proteins were found to be more abundant in ZIKV patients, providing insights into the potential roles of these modifications in the infection.
Article
Multidisciplinary Sciences
Jing Kai Chang, Guoshou Teo, Yael Pewzner-Jung, Daniel J. Cuthbertson, Anthony H. Futerman, Markus R. Wenk, Hyungwon Choi, Federico Torta
Summary: In this study, an untargeted lipidomics workflow using Q-RAI DIA approach was proposed, which enables simultaneous identification and reproducible relative quantification of lipids. This method was validated using lipid extracts from human plasma and serum samples from CerS2 null mice, and several lipid species significantly different between groups were identified.
SCIENTIFIC REPORTS
(2023)
