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Advanced measurement and data storage technologies have enabled high-dimensional profiling of complex biological systems. For this, modern multiomics studies regularly produce datasets with hundreds of thousands of measurements per sample, enabling a new era of precision medicine. Correlation analysis is an important first step to gain deeper insights into the coordination and underlying processes of such complex systems. However, the construction of large correlation networks in modern high-dimensional datasets remains a major computational challenge owing to rapidly growing runtime and memory requirements. Here we address this challenge by introducing CorALS (Correlation Analysis of Large-scale (biological) Systems), an open-source framework for the construction and analysis of large-scale parametric as well as non-parametric correlation networks for high-dimensional biological data. It features off-the-shelf algorithms suitable for both personal and high-performance computers, enabling workflows and downstream analysis approaches. We illustrate the broad scope and potential of CorALS by exploring perspectives on complex biological processes in large-scale multiomics and single-cell studies.
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http://dx.doi.org/10.1038/s43588-023-00429-y | DOI Listing |
Cell Res
September 2025
Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
The pre-dimerization of endosome-localized RNA sensor Toll-like receptor 3 (TLR3) is required for its innate recognition, yet how TLR3 pre-dimers are formed and precisely primed for innate activation remains unclear. Here, we demonstrate that endosome-localized self RNA Rmrp directly binds to TLR3 and induces TLR3 dimerization in the early endosome but does not interact with endosome-localized TLR7, TLR8, TLR9 or cytoplasmic RNA sensor RIG-I under homeostatic conditions. Cryo-EM structure of Rmrp-TLR3 complex reveals a novel lapped conformation of TLR3 dimer engaged by Rmrp, which is distinct from the activation mechanism by dsRNA and the specific structural feature at the 3'-end of Rmrp is critical for its functional interaction with TLR3.
View Article and Find Full Text PDFFEBS J
September 2025
Neutron Scattering Division, Oak Ridge National Laboratory, USA.
Serine hydroxymethyltransferase (SHMT) is a critical enzyme in the one-carbon (1C) metabolism pathway catalyzing the reversible conversion of L-Ser into Gly and concurrent transfer of 1C unit to tetrahydrofolate (THF) to give 5,10-methylene-THF (5,10-MTHF), which is used in the downstream syntheses of biomolecules critical for cell proliferation. The cellular 1C metabolism is hijacked by many cancer types to support cancer cell proliferation, making SHMT a promising target for the design and development of novel small-molecule antimetabolite chemotherapies. To advance structure-assisted drug design, knowledge of SHMT catalysis is crucial, but can only be fully realized when the atomic details of each reaction step governed by the acid-base catalysis are elucidated by visualizing active site hydrogen atoms.
View Article and Find Full Text PDFFEBS J
September 2025
Department of Molecular Microbiology, John Innes Centre, Norwich, UK.
Understanding the molecular basis of regulated nitrogen (N) fixation is essential for engineering N-fixing bacteria that fulfill the demand of crop plants for fixed nitrogen, reducing our reliance on synthetic nitrogen fertilizers. In Azotobacter vinelandii and many other members of Proteobacteria, the two-component system comprising the anti-activator protein (NifL) and the Nif-specific transcriptional activator (NifA)controls the expression of nif genes, encoding the nitrogen fixation machinery. The NifL-NifA system evolved the ability to integrate several environmental cues, such as oxygen, nitrogen, and carbon availability.
View Article and Find Full Text PDFThe status of co-infection with porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) and type 2 (PRRSV-2) in Japan is poorly understood. A case of such co-infection was identified on a PRRSV-1 non-vaccinated farm in Kagoshima prefecture. Both PRRSV-1 and PRRSV-2 genomes were simultaneously detected in pig samples by RT-PCR, and molecular analysis confirmed PRRSV-1/PRRSV-2 co-infection in individual piglets.
View Article and Find Full Text PDFPestic Biochem Physiol
November 2025
Shanxi Key Laboratory of Nucleic Acid Biopesticides, Institute of Applied Biology, Shanxi University, Taiyuan, Shanxi 030006, China; School of Synthetic Biology, Shanxi University, Taiyuan, Shanxi 030006, China; School of Life Science, Shanxi University, Taiyuan, Shanxi 030006, China.
Glutamine: fructose-6-phosphate aminotransferase (GFAT) is the first rate-limiting enzyme in the hexosamine biosynthetic pathway, which plays a crucial role in various biological processes, including chitin metabolism in insects. Locusta migratoria, a widespread and highly destructive agricultural pest, poses a significant threat due to its rapid reproduction and long-distance migration. In this study, we identified and characterized LmGFAT as a key regulator of locust development.
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