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| http://dx.doi.org/10.3350/cmh.2024.0558 | DOI Listing |
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Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma.
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Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY, USA.
Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer characterized by a fusion oncokinase of the genes DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). A few FLC-like tumors have been reported showing other alterations involving PKA. To better understand FLC pathogenesis and the relationships among FLC, FLC-like, and other liver tumors, we performed a massive multi-omics analysis.
View Article and Find Full Text PDFComputational design of potent dimeric phenylthiazole NS5A inhibitors for hepatitis C virus.
Sci Rep
December 2024
Bioinformatics Laboratory, College of Computing, University Mohammed VI Polytechnic, Ben Guerir, Morocco.
Hepatitis C virus (HCV) presents a significant global health issue due to its widespread prevalence and the absence of a reliable vaccine for prevention. While significant progress has been achieved in therapeutic interventions since the disease was first identified, its resurgence underscores the need for innovative strategies to combat it. The nonstructural protein NS5A is crucial in the life cycle of the HCV, serving as a significant factor in both viral replication and assembly processes.
View Article and Find Full Text PDFAlleviating batch effects in cell type deconvolution with SCCAF-D.
Nat Commun
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GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Laboratory, Guangzhou Medical University, Guangzhou, China.
Cell type deconvolution methods can impute cell proportions from bulk transcriptomics data, revealing changes in disease progression or organ development. But benchmarking studies often use simulated bulk data from the same source as the reference, which limits its application scenarios. This study examines batch effects in deconvolution and introduces SCCAF-D, a computational workflow that ensures a Pearson Correlation Coefficient above 0.
View Article and Find Full Text PDFIntegrated multi-omics profiling reveals neutrophil extracellular traps potentiate Aortic dissection progression.
Nat Commun
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Department of Vascular Surgery, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
Adverse aortic remodeling increases the risk of aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) and affects the overall prognosis of aortic dissection (AD). It is imperative to delve into the exploration of prognostic indicators to streamline the identification of individuals at elevated risk for postoperative AAEs, and therapeutic targets to optimize the efficacy of TEVAR for patients with AD. Here, we perform proteomic and single-cell transcriptomic analyses of peripheral blood and aortic lesions, respectively, from patients with AD and healthy subjects.
View Article and Find Full Text PDFEnhancing gene transfer to renal tubules and podocytes by context-dependent selection of AAV capsids.
Nat Commun
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Department of Molecular and Medical Genetics, Oregon Health & Science University School of Medicine, Portland, OR, USA.
AAV vectors show promise for gene therapy; however, kidney gene transfer remains challenging. Here we conduct a barcode-seq-based comparison of 47 AAV capsids administered through different routes in mice, followed by individual validation. We find that local delivery of AAV-KP1, but not AAV9, via the renal vein or pelvis effectively transduces proximal tubules with minimal off-target liver transduction, while systemic AAV9, but not AAV-KP1, enhances proximal tubule and podocyte transduction in chronic kidney disease.
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