Article
Biochemical Research Methods
Denis Beslic, Georg Tscheuschner, Bernhard Y. Renard, Michael G. Weller, Thilo Muth
Summary: Monoclonal antibodies are important proteins used in research, therapeutics, and diagnostics. Mass spectrometry-based de novo protein sequencing is a valuable method to obtain amino acid sequences without prior knowledge. Evaluating different sequencing algorithms is crucial for improving accuracy and coverage.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Gaurav Bhardwaj, Jacob O'Connor, Stephen Rettie, Yen-Hua Huang, Theresa A. Ramelot, Vikram Khipple Mulligan, Gizem Gokce Alpkilic, Jonathan Palmer, Asim K. Bera, Matthew J. Bick, Maddalena Di Piazza, Xinting Li, Parisa Hosseinzadeh, Timothy W. Craven, Roberto Tejero, Anna Lauko, Ryan Choi, Calina Glynn, Linlin Dong, Robert Griffin, Wesley C. van Voorhis, Jose Rodriguez, Lance Stewart, Gaetano T. Montelione, David Craik, David Baker
Summary: This study investigates the design principles for macrocycle membrane permeability and oral bioavailability using computational design and experimental characterization. The results show that membrane permeability can be achieved by engaging all amide (NH) groups in internal hydrogen bonding interactions. Additionally, designs with exposed NH groups can be made membrane permeable through the design of an alternative isoenergetic fully hydrogen-bonded state favored in the lipid membrane. The ability to design membrane-permeable and orally bioavailable peptides with high structural accuracy has significant implications for the development of next-generation macrocycle therapeutics.
Article
Chemistry, Analytical
Cuitong He, Catherine C. L. Wong
Summary: Alternative splicing of human genes allows the production of diverse proteoforms, which play crucial roles in normal and disease physiology. However, the discovery of low-abundance proteoforms is limited by current detection methods. This study presents the development of a novel algorithm, CNovo, which outperforms existing algorithms. Furthermore, a semi-de novo sequencing algorithm, SpliceNovo, specifically designed for identifying novel junction peptides, demonstrates higher accuracy than other algorithms. Our results significantly enhance the identification of novel proteoforms through de novo sequencing.
ANALYTICAL CHEMISTRY
(2023)
Review
Spectroscopy
Albert T. Lebedev, Irina D. Vasileva, Tatiana Y. Samgina
Summary: The present review discusses the application of FT-MS for de novo sequencing of natural peptides from various animals. These peptides are bioactive and are used by animals as a weapon against microorganisms and predators. They have potential as drugs of the future generation, as their mechanism of action is different from modern antibiotics. De novo sequencing becomes challenging when the species genome is unavailable and little is known about the peptides. The benefits of FT-MS for top-down peptide sequencing and the difficulties encountered in sequence elucidation are discussed.
MASS SPECTROMETRY REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Ema Svetlicic, Lucija Doncevic, Luka Ozdanovac, Andrea Janes, Tomislav Tustonic, Andrija Stajduhar, Antun Lovro Brkic, Marina Ceprnja, Mario Cindric
Summary: This study proposes a mass spectrometry-based method for rapid and accurate identification of microbial pathogens, overcoming the limitations of traditional methods. The method utilizes a novel instrument for pathogen identification without the need for a lengthy culture step, and employs a more comprehensive database for species identification.
Article
Multidisciplinary Sciences
Simone Koenig, Heather G. G. Marco, Gerd Gade
Summary: Through the analysis of AKHs in various insects, specific fragmentation patterns were discovered, which were related to the presence of Pro at position 6, providing relevant information for sequence elucidation. Additionally, the presence of Trp at position 8 allowed for the identification of candidate AKHs.
SCIENTIFIC REPORTS
(2023)
Article
Genetics & Heredity
Randy Ortiz, Priyanka Gera, Christopher Rivera, Juan C. Santos
Summary: Transcriptomic reconstructions without reference are common for non-model biological systems, but the lack of standardization and customization in bioinformatic workflows poses challenges. The increasing number of transcriptome assembly software further complicates the issue, highlighting the need for studies on assembler synergy and the development of customizable management workflows.
Article
Biochemical Research Methods
Tatiana Y. Samgina, Maria D. Tolpina, Alexey K. Surin, Sergey V. Kovalev, Roberto Alonso Bosch, Isel Pascual Alonso, Fabiola Almeida Garcia, Luis Javier Gonzalez Lopez, Albert T. Lebedev
Summary: The skin glands of amphibians contain host defense peptides that form the basis of their adaptive and immune system. In this study, the peptidome of the Cuban frog Osteopilus septentrionalis was established using tandem mass spectrometry. Surprisingly, only anionic peptides were identified in the frog skin secretion, leading to the discovery of 16 representatives of new peptide families, including septenins 1 and septenins 2. Mirror-symmetrical peptides were sequenced using N-terminal acetylation, and the physicochemical and structural properties of the discovered anionic peptides allowed the mechanism of their interaction with microbe cells to be postulated.
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
(2021)
Article
Biochemistry & Molecular Biology
Tatiana Yu. Samgina, Irina D. Vasileva, Polonca Trebse, Gregor Torkar, Alexey K. Surin, Zhaowei Meng, Roman A. Zubarev, Albert T. Lebedev
Summary: Peptides released on frogs' skin in a stress situation are their only weapon against micro-organisms and predators. Each frog population has its own unique peptidome suitable for their habitat. This study analyzed the peptidome composition of the Central Slovenian agile frog population, and discovered multiple peptide families.
Article
Microbiology
Katie Vigil, Tiong Gim Aw
Summary: This study utilized long-read nanopore sequencing to perform viral metagenomics on stool and serum samples from California sea lions and bottlenose dolphins. Two popular long-read de novo assemblers, Canu and Metaflye, were compared for assembling viral metagenomic sequencing reads from marine mammals. The results showed that both Canu and Metaflye could assemble similar viral contigs of vertebrates, but Canu outperformed Metaflye by assembling viral contigs that aligned with more viral families. Canu also assembled viral contigs from dolphin and sea lion fecal samples that matched both protein and nucleotide RefSeq viral databases, suggesting the importance of marine mammals in surveillance of marine viruses.
FRONTIERS IN MICROBIOLOGY
(2023)
Review
Medicine, Research & Experimental
Sebastiaan C. de Graaf, Max Hoek, Sem Tamara, Albert J. R. Heck
Summary: Identifying the amino acid sequence is a crucial step in analyzing therapeutic and endogenous humoral antibodies. Mass spectrometry has emerged as a viable alternative to nucleotide sequencing for obtaining sequence information at the protein level. However, sequencing recombinant and endogenous antibodies using mass spectrometry presents specific challenges that go beyond conventional proteomics workflows.
Article
Chemistry, Analytical
Zhi-Biao Mai, Zhong-Hua Zhou, Qing-Yu He, Gong Zhang
Summary: This article introduces a contig-scaffolding strategy for high robustness and accuracy in protein sequence assembly. The strategy minimizes bias in the hydrolysis process by integrating multiple unspecific hydrolysis methods and uses a multistep assembly algorithm with error correction. Experimental results demonstrate the effectiveness of this strategy in assembling protein sequences with high coverage and accuracy, even for membrane proteins.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Joon-Yong Lee, Hugh D. Mitchell, Meagan C. Burnet, Ruonan Wu, Sarah C. Jenson, Eric D. Merkley, Ernesto S. Nakayasu, Carrie D. Nicora, Janet K. Jansson, Kristin E. Burnum-Johnson, Samuel H. Payne
Summary: Metaproteomics is increasingly used for high-throughput characterization of proteins in complex environments, and the creation of a sample-specific protein sequence database is crucial for accurate analysis. This study presents a de novo peptide sequencing approach to identify sample composition directly from metaproteomic data, using a deep learning model trained on diverse bacteria. The results demonstrate the potential of this method as an alternative and complementary approach to construct sample-specific protein databases, particularly in the absence of matched metagenomes.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Biochemical Research Methods
Xingyu Liao, Min Li, Junwei Luo, You Zou, Fang-Xiang Wu, Yi-Pan, Feng Luo, Jianxin Wang
Summary: This study introduces a new framework, EPGA-SC, for de novo assembly of single-cell sequencing data, overcoming challenges such as sequencing errors, biases, and repetitive regions. By classifying reads, using high precision paired-end reads from other assemblers, and developing novel algorithms for error removal and contig extension, EPGA-SC outperforms most current tools in terms of MAX contig, N50, NG50, NA50, and NGA50.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Entomology
Li Hu, Yae Zhao, Wanyu Zhang
Summary: This study successfully sequenced the transcriptome of D. canis for the first time, performed functional annotation, and verified the presence of important functional genes. This provides valuable data for further research on the functional genes and molecular pathogenic mechanism of D. canis.
EXPERIMENTAL AND APPLIED ACAROLOGY
(2022)
Article
Microbiology
R. Jason Lamontagne, Samantha S. Soldan, Chenhe Su, Andreas Wiedmer, Kyoung Jae Won, Fang Lu, Aaron R. Goldman, Jayamanna Wickramasinghe, Hsin-Yao Tang, David W. Speicher, Louise Showe, Andrew V. Kossenkov, Paul M. Lieberman
Summary: EBV immortalizes resting B-lymphocytes through orchestrated reprogramming of chromatin structure, transcription, and metabolism. The virus alters accessible chromatin, leading to complex transcriptional responses and changes in nucleotide metabolism. Purine metabolism, particularly the role of adenosine deaminase, emerges as a major therapeutic target in EBV-driven lymphoid cancers. This study highlights the importance of purine metabolism and ADA in EBV-induced immortalization process.
Article
Microbiology
Leila B. Giron, Emmanouil Papasavvas, Xiangfan Yin, Aaron R. Goldman, Hsin-Yao Tang, Clovis S. Palmer, Alan L. Landay, Jonathan Z. Li, John R. Koethe, Karam Mounzer, Jay R. Kostman, Qin Liu, Luis J. Montaner, Mohamed Abdel-Mohsen
Summary: The study revealed a potential link between high levels of lysophosphatidylcholine and its derivatives with faster viral rebound and higher viral load post-ART in HIV-infected individuals. Additionally, the lysophosphatidylcholine precursor showed strong correlation with pre-ART HIV DNA levels, suggesting a role of lipid metabolism in shaping host immune and inflammatory responses during and after ART.
Article
Medicine, Research & Experimental
Iart Luca Shytaj, Francesco Andrea Procopio, Mohammad Tarek, Irene Carlon-Andres, Hsin-Yao Tang, Aaron R. Goldman, MohamedHusen Munshi, Virender Kumar Pal, Mattia Forcato, Sheetal Sreeram, Konstantin Leskov, Fengchun Ye, Bojana Lucic, Nicolly Cruz, Lishomwa C. Ndhlovu, Silvio Bicciato, Sergi Padilla-Parra, Ricardo Sobhie Diaz, Amit Singh, Marina Lusic, Jonathan Karn, David Alvarez-Carbonell, Andrea Savarino
Summary: The study reveals that latent HIV-1 infection downregulates glycolysis and relies on the pentose phosphate pathway for maintaining latency. Reactivation of the virus can revert this effect and decrease proviral DNA in infected cells.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Daniela Di Marcantonio, Esteban Martinez, Joice S. Kanefsky, Jacklyn M. Huhn, Rashid Gabbasov, Anushk Gupta, John J. Krais, Suraj Peri, YinFei Tan, Tomasz Skorski, Adrienne Dorrance, Ramiro Garzon, Aaron R. Goldman, Hsin-Yao Tang, Neil Johnson, Stephen M. Sykes
Summary: The study reveals that AML relies on ATF3-regulated serine and nucleotide metabolism, with ATF3 inhibition leading to reduced serine synthesis, impediments in carbon incorporation into new purines, and disruption of pyrimidine metabolism.
Article
Multidisciplinary Sciences
Leila B. Giron, Clovis S. Palmer, Qin Liu, Xiangfan Yin, Emmanouil Papasavvas, Radwa Sharaf, Behzad Etemad, Mohammad Damra, Aaron R. Goldman, Hsin-Yao Tang, Rowena Johnston, Karam Mounzer, Jay R. Kostman, Pablo Tebas, Alan Landay, Luis J. Montaner, Jeffrey M. Jacobson, Jonathan Z. Li, Mohamed Abdel-Mohsen
Summary: The study identified non-invasive plasma biomarkers that predict both the duration and probability of HIV remission after treatment interruption. These biomarkers were validated in two independent cohorts and were found to be associated with HIV latency reactivation and inflammatory pathways.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Chenhe Su, Fang Lu, Samantha S. Soldan, R. Jason Lamontagne, Hsin-Yao Tang, Giorgia Napoletani, Paul J. Farrell, Italo Tempera, Andrew V. Kossenkov, Paul M. Lieberman
Summary: The study reveals a new transcriptional mechanism by which EBV encoded EBNA2 down-regulates HLA class II gene expression, impacting T-cell recognition of infected cells. EBNA2 competes with CIITA binding, leading to CIITA transcriptional down-regulation and subsequent HLA-II gene expression attenuation. This indirect regulation is proposed to be due to enhancer competition at neighboring chromosome domains.
Article
Multidisciplinary Sciences
Ekta Agarwal, Aaron R. Goldman, Hsin-Yao Tang, Andrew V. Kossenkov, Jagadish C. Ghosh, Lucia R. Languino, Valentina Vaira, David W. Speicher, Dario C. Altieri
Summary: Parkin, an E3 ubiquitin ligase altered in Parkinson's disease, is shown to suppress tumor growth by shutting off mitochondrial dynamics and inhibiting the non-oxidative phase of the pentose phosphate pathway. This tumor suppression function of Parkin requires its E3 ligase activity and can be reversed by antioxidants, independently of mitophagy. Cancer metabolic networks are identified as potential oncogenes directly targeted by endogenous tumor suppression mechanisms.
Article
Multidisciplinary Sciences
Jagadish C. Ghosh, Michela Perego, Ekta Agarwal, Irene Bertolini, Yuan Wang, Aaron R. Goldman, Hsin-Yao Tang, Andrew Kossenkov, Catherine J. Libby, Lucia R. Languino, Edward F. Plow, Annamaria Morotti, Luisa Ottobrini, Marco Locatelli, David W. Speicher, M. Cecilia Caino, Joel Cassel, Joseph M. Salvino, Marie E. Robert, Valentina Vaira, Dario C. Altieri
Summary: The study reveals that many human tumors have reduced levels of Mic60, an essential scaffold of mitochondrial structure, which leads to the disruption of mitochondrial integrity. Surprisingly, these tumors show decreased cell proliferation, resistance to cell death, and activation of a gene expression program related to innate immunity and cytokine/chemokine signaling. This process induces epithelial-mesenchymal transition, tumor cell movement, and promotes metastatic dissemination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Evgenii N. Tcyganov, Emilio Sanseviero, Douglas Marvel, Thomas Beer, Hsin-Yao Tang, Peter Hembach, David W. Speicher, Qianfei Zhang, Laxminarasimha R. Donthireddy, Ali Mostafa, Sabina Tsyganova, Vladimir Pisarev, Terri Laufer, Dmitriy Ignatov, Soldano Ferrone, Christiane Meyer, Helene Maby-El Hajjami, Daniel E. Speiser, Sooner Altiok, Scott Antonia, Xiaowei Xu, Wei Xu, Cathy Zheng, Lynn M. Schuchter, Ravi K. Amaravadi, Tara C. Mitchell, Giorgos C. Karakousis, Zhe Yuan, Luis J. Montaner, Esteban Celis, Dmitry Gabrilovich
Summary: This study found that the oxidant peroxynitrite (PNT) can alter the profile of MHC-I bound peptides presented on tumor cells. Only cytotoxic cells targeting PNT-resistant peptides have an anti-tumor effect, while those targeting PNT-sensitive peptides are ineffective. Targeting PNT in mice reduces tumor cell resistance to cytotoxic cells. Melanoma patients with low PNT activity in their tumors respond better to immunotherapy.
Article
Immunology
Gauri Mirji, Alison Worth, Sajad Ahmad Bhat, Mohamed El Sayed, Toshitha Kannan, Aaron R. Goldman, Hsin-Yao Tang, Qin Liu, Noam Auslander, Chi Dang, Mohamed Abdel-Mohsen, Andrew Kossenkov, Ben Z. Stanger, Rahul S. Shinde
Summary: The gut microbe-derived metabolite TMAO enhances antitumor immunity in pancreatic ductal adenocarcinoma (PDAC) by promoting an immunostimulatory tumor-associated macrophage (TAM) phenotype and activating effector T cell response. TMAO exerts antitumor effects through potentiating the type I interferon pathway.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Minjeong Yeon, Irene Bertolini, Ekta Agarwal, Jagadish C. Ghosh, Hsin-Yao Tang, David W. Speicher, Frederick Keeney, Khalid Sossey-Alaoui, Elzbieta Pluskota, Katarzyna Bialkowska, Edward F. Plow, Lucia R. Languino, Emmanuel Skordalakes, M. Cecilia Caino, Dario C. Altieri
Summary: In this study, it is found that the altered ubiquitination ligase Parkin in Parkinson's disease forms a complex with the regulator of cell motility Kindlin-2 at mitochondria of tumor cells. Parkin ubiquitinates Kindlin-2 leading to its proteasomal degradation, which inhibits tumor cell interactions with the extracellular matrix, migration, and invasion. However, Parkin does not affect tumor cell proliferation, cell cycle transitions, or apoptosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Brittany MacTaggart, Marie Shimogawa, Marshall Lougee, Hsin-Yao Tang, E. J. Petersson, Anna Kashina
Summary: This study reports the first global screen for side-chain arginylation and generates and validates panarginylation antibodies for detecting side-chain arginylation in any amino acid sequence context. The study identifies a limited set of proteins that likely undergo ATE1-dependent side-chain arginylation and are enriched in specific cellular roles.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Oncology
Simona Lombardi, Aaron R. Goldman, Hsin-Yao Tang, Andrew Kossenkov, Heng Liu, Wei Zhou, Meenhard Herlyn, Jianhuang Lin, Rugang Zhang
Summary: The arginine methyltransferase CARM1 is highly expressed in various human cancers, including ovarian cancer, but therapeutic approaches for tumors overexpressing CARM1 have not been studied. This study found that CARM1 promotes monounsaturated fatty acid synthesis and targeting the fatty acid reprogramming pathway can be a potential therapeutic strategy for CARM1-expressing ovarian cancers.
CANCER RESEARCH COMMUNICATIONS
(2023)
Article
Immunology
Leila B. Giron, Harsh Dweep, Xiangfan Yin, Han Wang, Mohammad Damra, Aaron R. Goldman, Nicole Gorman, Clovis S. Palmer, Hsin-Yao Tang, Maliha W. Shaikh, Christopher B. Forsyth, Robert A. Balk, Netanel F. Zilberstein, Qin Liu, Andrew Kossenkov, Ali Keshavarzian, Alan Landay, Mohamed Abdel-Mohsen
Summary: The disruption of crosstalk between the gut and lung is implicated as a driver of severity in respiratory-related diseases. Severe COVID-19 is associated with high levels of markers indicating disrupted gut permeability, microbial translocation, and systemic inflammation, which correlate strongly with other disruptions in the body and higher mortality rates. It highlights the importance of gut functions in contributing to the severity of COVID-19.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Xuanmao Jiao, Min Wang, Zhao Zhang, Zhiping Li, Dong Ni, Anthony W. Ashton, Hsin-Yao Tang, David W. Speicher, Richard G. Pestell
Summary: Leronlimab has shown potential in binding to CCR5 in multiple breast cancer cell lines, reducing invasion and migration of TNBC, and enhancing the effect of chemotherapy reagent doxorubicin on breast cancer cells. In mouse xenografts, leronlimab significantly reduced lung metastasis of TNBC cell line MB-MDA-231 and decreased the metastatic tumor burden of established TNBC lung metastasis. These promising results suggest further studies on the clinical efficacy of leronlimab in breast cancer may be warranted.
BREAST CANCER RESEARCH
(2021)