Article
Chemistry, Medicinal
Timothy R. Stachowski, Marcus Fischer
Summary: Protein flexibility is crucial in drug design, especially for targeting dynamic proteins like Hsp90. The analysis of Hsp90 alpha crystal structures revealed different conformations of the lid domain that accommodate chemically distinct ligands. This study highlights the importance of considering protein ensembles and warns against overinterpreting individual crystal structures in drug design.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Austin S. Draycott, Cassandra Schaening-Burgos, Maria F. Rojas-Duran, Loren Wilson, Leonard Scharfen, Karla M. Neugebauer, Sigrid Nachtergaele, Wendy Gilbert
Summary: The study introduces a new sequencing technique called D-seq to map dihydrouridine (D) with single-nucleotide resolution in the transcriptome. Novel classes of D-containing RNA, including mRNA and snoRNA, are discovered in yeast. The D sites are concentrated in conserved stem-loop regions and are involved in splicing of pre-mRNA and translation of mRNA.
Article
Cell Biology
Tulsi Patel, Troy P. Carnwath, Xue Wang, Mariet Allen, Sarah J. Lincoln, Laura J. Lewis-Tuffin, Zachary S. Quicksall, Shu Lin, Frederick Q. Tutor-New, Charlotte C. G. Ho, Yuhao Min, Kimberly G. Malphrus, Thuy T. Nguyen, Elizabeth Martin, Cesar A. Garcia, Rawan M. Alkharboosh, Sanjeet Grewal, Kaisorn Chaichana, Robert Wharen, Hugo Guerrero-Cazares, Alfredo Quinones-Hinojosa, Nilufer Ertekin-Taner
Summary: This study comprehensively characterizes the transcriptomes of human microglia and explores the effects of age, sex, and APOE. The study identifies microglial co-expression network modules associated with age, sex, and APOE-epsilon 4 that are enriched for lipid and carbohydrate metabolism genes. These modules and disease-associated microglial clusters contain known neurodegenerative disease genes.
Article
Multidisciplinary Sciences
Dilara Uzuner, Yunus Akkoc, Nesibe Peker, Pinar Pir, Devrim Gozuacik, Tunahan Cakir
Summary: The study investigated 10 transcriptomic datasets, identifying 139 genes and 1974 interactions, constructing a dormancy interaction network contributing to the elucidation of cellular mechanisms orchestrating cancer dormancy, paving the way for improvements in the diagnosis and treatment of metastatic cancer.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Ivan Litvinov, Pingxing Xie, Scott Gunn, Denis Sasseville, Philippe Lefrancois
Summary: Basal cell carcinoma is the most common skin cancer, but still poses challenges in treatment. By analyzing RNA sequencing data, new therapeutic avenues and potential targets have been identified, providing new insights for treating BCC.
LIFE SCIENCE ALLIANCE
(2021)
Article
Genetics & Heredity
Junling Pang, Ya Luo, Dong Wei, Zhujie Cao, Xianmei Qi, Meiyue Song, Ying Liu, Zhaoguo Li, Jin Zhang, Baicun Li, Jingyu Chen, Jing Wang, Chen Wang
Summary: This study conducted RNA sequencing on lung tissues of silicosis patients and non-diseased donors, identifying 2605 differentially expressed genes and critical pathway changes. Comparative analysis with idiopathic pulmonary fibrosis and chronic obstructive pulmonary diseases revealed common and specific regulations in silicosis, as well as potential drug targets. Through transcriptome analyses, valuable cues for silicosis treatment were provided.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Charlotte Rypens, Francois Bertucci, Pascal Finetti, Fredika Robertson, Sandra Fernandez, Naoto Ueno, Wendy A. Woodward, Kenneth Van Golen, Peter Vermeulen, Luc Dirix, Patrice Viens, Daniel Birnbaum, Gayathri R. Devi, Massimo Cristofanilli, Steven Van Laere
Summary: In this study, the transcriptome of a series of inflammatory breast cancer (IBC) preclinical models was evaluated and compared to patient samples. It was found that the IBC preclinical models are predominantly estrogen receptor-negative and of the basal-like subtype, which is similar to the molecular characteristics observed in patients. The study also revealed important roles for cell proliferation, MYC transcriptional activity, and TNF alpha/NF kappa B in IBC biology.
Review
Transplantation
Manikkam Suthanthiran
Summary: Due to the contribution of all functioning nephrons to urine formation, urine is considered a suitable substitute for kidney allograft biopsy in determining the status of human kidney allografts. By performing RNA sequencing of urinary cells and kidney allograft biopsies, the transcriptional landscape of allograft rejection can be defined. Recent findings have identified unique and shared gene signatures of acute T cell mediated rejection and antibody mediated rejection through whole genome transcriptome profiling. The enrichment of rejection signatures in urinary cells suggests that urinary cell mRNA profiles can serve as diagnostic and prognostic indicators of acute rejection.
CURRENT OPINION IN ORGAN TRANSPLANTATION
(2023)
Article
Cell Biology
Piero Dalle Pezze, Eleftherios Karanasios, Varvara Kandia, Maria Manifava, Simon A. Walker, Nicolas Gambardella Le Novere, Nicholas T. Ktistakis
Summary: The study found that the translocation of ATG13 during autophagy is influenced by different stimuli and drugs, with multiple translocations observed during mitophagy. The mathematical model supports the hypothesis that the number of ATG13 translocations is directly proportional to the diameter of the targeted mitochondrial fragments, providing new insights into the early dynamics of selective and nonselective autophagy.
Review
Biochemical Research Methods
Tallulah S. Andrews, Vladimir Yu Kiselev, Davis McCarthy, Martin Hemberg
Summary: Single-cell RNA sequencing (scRNA-seq) is a popular and powerful technology for profiling the whole transcriptome of individual cells, but analyzing the large volumes of data requires specialized statistical and computational methods. This article provides an overview of the computational workflow, common tasks and tools for addressing biological questions, as well as guidelines for best practices in computational analyses. It serves as a hands-on guide for experimentalists and an overview for bioinformaticians developing new computational methods.
Article
Biochemical Research Methods
Jimmy Tsz Hang Lee, Nikolaos Patikas, Vladimir Yu Kiselev, Martin Hemberg
Summary: scfind is a single-cell analysis tool that enables fast search of marker genes in cell atlases, in silico gating, and identification of cell-type-specific and housekeeping genes. It utilizes various technologies to ensure meaningful results for long and complex queries.
Article
Immunology
Daisy H. Luff, Katarzyna Wojdyla, David Oxley, Tamara Chessa, Kevin Hudson, Phillip T. Hawkins, Len R. Stephens, Simon T. Barry, Klaus Okkenhaug
Summary: In T cells, PI3K delta rapidly interacts with multiple adaptor proteins, including GAB family proteins, ICOS, and TRIM, and pre-forms complexes to facilitate its activation at the plasma membrane. There is a large protein network in CD4(+) T cells that regulates the recruitment and activation of PI3K delta. The PI3K delta interactome undergoes remodeling at different stages of T cell differentiation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Emily Stephenson, Gary Reynolds, Rachel A. Botting, Fernando J. Calero-Nieto, Michael D. Morgan, Zewen Kelvin Tuong, Karsten Bach, Waradon Sungnak, Kaylee B. Worlock, Masahiro Yoshida, Natsuhiko Kumasaka, Katarzyna Kania, Justin Engelbert, Bayan Olabi, Jarmila Stremenova Spegarova, Nicola K. Wilson, Nicole Mende, Laura Jardine, Louis C. S. Gardner, Issac Goh, Dave Horsfall, Jim McGrath, Simone Webb, Michael W. Mather, Rik G. H. Lindeboom, Emma Dann, Ni Huang, Krzysztof Polanski, Elena Prigmore, Florian Gothe, Jonathan Scott, Rebecca P. Payne, Kenneth F. Baker, Aidan T. Hanrath, Ina C. D. Schim van der Loeff, Andrew S. Barr, Amada Sanchez-Gonzalez, Laura Bergamaschi, Federica Mescia, Josephine L. Barnes, Eliz Kilich, Angus de Wilton, Anita Saigal, Aarash Saleh, Sam M. Janes, Claire M. Smith, Nusayhah Gopee, Caroline Wilson, Paul Coupland, Jonathan M. Coxhead, Vladimir Yu Kiselev, Stijn van Dongen, Jaume Bacardit, Hamish W. King, Anthony J. Rostron, A. John Simpson, Sophie Hambleton, Elisa Laurenti, Paul A. Lyons, Kerstin B. Meyer, Marko Z. Nikolic, Christopher J. A. Duncan, Kenneth G. C. Smith, Sarah A. Teichmann, Menna R. Clatworthy, John C. Marioni, Berthold Gottgens, Muzlifah Haniffa
Summary: Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.
Article
Mathematical & Computational Biology
Hasan Baig, Pedro Fontanarossa, Vishwesh Kulkarni, James McLaughlin, Prashant Vaidyanathan, Bryan Bartley, Shyam Bhakta, Swapnil Bhatia, Mike Bissell, Kevin Clancy, Robert Sidney Cox, Angel Goni Moreno, Thomas Gorochowski, Raik Grunberg, Jihwan Lee, Augustin Luna, Curtis Madsen, Goksel Misirli, Tramy Nguyen, Nicolas Le Novere, Zachary Palchick, Matthew Pocock, Nicholas Roehner, Herbert Sauro, James Scott-Brown, John T. Sexton, Guy-Bart Stan, Jeffrey J. Tabor, Logan Terry, Marta Vazquez Vilar, Christopher A. Voigt, Anil Wipat, David Zong, Zach Zundel, Jacob Beal, Chris Myers
Summary: SBOL Visual is a standard for organizing diagrams in biological engineering, and the latest version 2.3 includes higher-level interactions and more visual options for genetic designs.
JOURNAL OF INTEGRATIVE BIOINFORMATICS
(2021)
Article
Genetics & Heredity
Luz Garcia-Alonso, Louis-Francois Handfield, Kenny Roberts, Konstantina Nikolakopoulou, Ridma C. Fernando, Lucy Gardner, Benjamin Woodhams, Anna Arutyunyan, Krzysztof Polanski, Regina Hoo, Carmen Sancho-Serra, Tong Li, Kwasi Kwakwa, Elizabeth Tuck, Valentina Lorenzi, Hassan Massalha, Martin Prete, Vitalii Kleshchevnikov, Aleksandra Tarkowska, Tarryn Porter, Cecilia Icoresi Mazzeo, Stijn van Dongen, Monika Dabrowska, Vasyl Vaskivskyi, Krishnaa T. Mahbubani, Jong-Eun Park, Mercedes Jimenez-Linan, Lia Campos, Vladimir Yu. Kiselev, Cecilia Lindskog, Paul Ayuk, Elena Prigmore, Michael R. Stratton, Kourosh Saeb-Parsy, Ashley Moffett, Luiza Moore, Omer A. Bayraktar, Sarah A. Teichmann, Margherita Y. Turco, Roser Vento-Tormo
Summary: Researchers have analyzed the dynamic changes of the human endometrium using single-cell and spatial transcriptomic profiling, revealing the regulatory role of WNT and NOTCH signaling pathways in differentiation into secretory and ciliated epithelial lineages.
Article
Multidisciplinary Sciences
Javier Rodriguez-Ubreva, Anna Arutyunyan, Marc Jan Bonder, Lucia Del Pino-Molina, Stephen J. Clark, Carlos de la Calle-Fabregat, Luz Garcia-Alonso, Louis-Francois Handfield, Laura Ciudad, Eduardo Andres-Leon, Felix Krueger, Francesc Catala-Moll, Virginia C. Rodriguez-Cortez, Krzysztof Polanski, Lira Mamanova, Stijn van Dongen, Vladimir Yu Kiselev, Maria T. Martinez-Saavedra, Holger Heyn, Javier Martin, Klaus Warnatz, Eduardo Lopez-Granados, Carlos Rodriguez-Gallego, Oliver Stegle, Gavin Kelsey, Roser Vento-Tormo, Esteban Ballestar
Summary: In this study, single-cell omics analyses were performed in CVID-discordant monozygotic twins, revealing epigenetic and transcriptional alterations associated with activation in memory B cells. These findings provide valuable insights into the diagnosis and treatment of CVID patients.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Biochemistry & Molecular Biology
David Barneda, Len Stephens, Phillip Hawkins
Summary: Li et al. conducted a proximity-interaction screen in mammalian cells to study the effector proteins of 25 members of the Arf family of small GTPases. The study has provided an important resource for researchers in various areas of cell biology and revealed new cellular roles for some of the less studied members of this family, such as the regulation of PLD1 by ARL11/14 in phagocytosis and the regulation of PI4KB by ARL5A/5B in the Golgi.
Article
Biochemistry & Molecular Biology
David Barneda, Vishnu Janardan, Izabella Niewczas, Daniel M. Collins, Sabina Cosulich, Jonathan Clark, Len R. Stephens, Phillip T. Hawkins
Summary: Phosphoinositides (PIPn) with specific acyl chain composition can function as a molecular code for metabolic channelling from PIP2 to PI via pools of intermediates.
Article
Multidisciplinary Sciences
Luz Garcia-Alonso, Valentina Lorenzi, Cecilia Icoresi Mazzeo, Joao Pedro Alves-Lopes, Kenny Roberts, Carmen Sancho-Serra, Justin Engelbert, Magda Mareckova, Wolfram H. Gruhn, Rachel A. Botting, Tong Li, Berta Crespo, Stijn van Dongen, Vladimir Yu Kiselev, Elena Prigmore, Mary Herbert, Ashley Moffett, Alain Chedotal, Omer Ali Bayraktar, Azim Surani, Muzlifah Haniffa, Roser Vento-Tormo
Summary: The study generated a comprehensive map of human and mouse gonadal differentiation using single-cell and spatial transcriptomics, chromatin accessibility assays, and fluorescent microscopy. It identified human-specific regulatory programs and resolved the cellular and molecular events in gonadal development, providing guidance for in vitro gonadogenesis.
Correction
Genetics & Heredity
Luz Garcia-Alonso, Louis-Francois Handfield, Kenny Roberts, Konstantina Nikolakopoulou, Ridma C. Fernando, Lucy Gardner, Benjamin Woodhams, Anna Arutyunyan, Krzysztof Polanski, Regina Hoo, Carmen Sancho-Serra, Tong Li, Kwasi Kwakwa, Elizabeth Tuck, Valentina Lorenzi, Hassan Massalha, Martin Prete, Vitalii Kleshchevnikov, Aleksandra Tarkowska, Tarryn Porter, Cecilia Icoresi Mazzeo, Stijn van Dongen, Monika Dabrowska, Vasyl Vaskivskyi, Krishnaa T. Mahbubani, Jong-eun Park, Mercedes Jimenez-Linan, Lia Campos, Vladimir Yu. Kiselev, Cecilia Lindskog, Paul Ayuk, Elena Prigmore, Michael R. Stratton, Kourosh Saeb-Parsy, Ashley Moffett, Luiza Moore, Omer A. Bayraktar, Sarah A. Teichmann, Margherita Y. Turco, Roser Vento-Tormo
Article
Cell Biology
Aleksandra Somogyi, Emily D. Kirkham, Emyr Lloyd-Evans, Jincy Winston, Nicholas D. Allen, John J. Mackrill, Karen E. Anderson, Phillip T. Hawkins, Sian E. Gardiner, Helen Waller-Evans, Rebecca Sims, Barry Boland, Cora O'Neill
Summary: Abnormalities in the EAL system are early events in AD pathogenesis, but the mechanisms are unclear. TRPML1 dysregulation is found in LOAD neurons, leading to increased clustering and vacuolation of endolysosomes. Diminished TRPML1-induced endolysosomal Ca2+ release and EAL neuropathology in LOAD can be recreated by blocking TRPML1 function and rescued by TRPML1 reactivation.
JOURNAL OF CELL SCIENCE
(2023)
Article
Genetics & Heredity
Batuhan Cakir, Martin Prete, Ni Huang, Stijn van Dongen, Pinar Pir, Vladimir Yu Kiselev
NAR GENOMICS AND BIOINFORMATICS
(2020)
Article
Mathematical & Computational Biology
Hasan Baig, Pedro Fontanarrosa, Vishwesh Kulkarni, James McLaughlin, Prashant Vaidyanathan, Bryan Bartley, Swapnil Bhatia, Shyam Bhakta, Michael Bissell, Kevin Clancy, Robert Sidney Cox, Angel Goni Moreno, Thomas Gorochowski, Raik Grunberg, Augustin Luna, Curtis Madsen, Goksel Misirli, Tramy Nguyen, Nicolas Le Novere, Zachary Palchick, Matthew Pocock, Nicholas Roehner, Herbert Sauro, James Scott-Brown, John T. Sexton, Guy-Bart Stan, Jeffrey J. Tabor, Marta Vazquez Vilar, Christopher A. Voigt, Anil Wipat, David Zong, Zach Zundel, Jacob Beal, Chris Myers
JOURNAL OF INTEGRATIVE BIOINFORMATICS
(2020)