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Protein lipoylation in cancer: metabolic reprogramming and therapeutic potential
Cell Death Discovery, Published online: 02 September 2025; doi:10.1038/s41420-025-02718-z
Protein lipoylation in cancer: metabolic reprogramming and therapeutic potentialAn organoid co-culture model for probing systemic anti-tumor immunity in lung cancer
Cell Stem Cell. 2025 Jun 6:S1934-5909(25)00191-2. doi: 10.1016/j.stem.2025.05.011. Online ahead of print.
ABSTRACT
Deciphering interactions between tumor micro- and systemic immune macroenvironments is essential for developing more effective cancer diagnosis and therapeutic strategies. Here, we established a gel-liquid interface (GLI) co-culture model of lung cancer organoids (LCOs) and paired peripheral-blood mononuclear cells (PBMCs), featuring enhanced interactions between immune cells and tumor organoids for optimized simulation of in vivo systemic anti-tumor immunity. By constructing a cohort of lung cancer patients, we demonstrated that the responses of GLI models under αPD1 treatment reflected the immunotherapy outcomes of the corresponding patients precisely. Furthermore, we dissected the various tumor immune processes mediated by PBMC-derived T cells within GLI models through functional multi-omics analyses, along with the characterization of circulating tumor-reactive T cells (GNLY+CD44+CD9+) with effector memory-like phenotypes as a potential indicator of immunotherapy efficacy. Our findings indicate that the GLI co-culture model can be used to develop diagnostic strategies for precision immunotherapies, as well as understanding the underlying mechanisms.
PMID:40513558 | DOI:10.1016/j.stem.2025.05.011
A statistical framework for multi-trait rare variant analysis in large-scale whole-genome sequencing studies
Nat Comput Sci. 2025 Feb 7. doi: 10.1038/s43588-024-00764-8. Online ahead of print.
ABSTRACT
Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally scalable analytical pipeline for functionally informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits in 61,838 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered and replicated new associations with lipid traits missed by single-trait analysis.
PMID:39920506 | DOI:10.1038/s43588-024-00764-8
Identification of novel germline mutations in <i>FUT7</i> and <i>EXT1</i> linked with hereditary multiple exostoses
Oncogene, Published online: 17 December 2024; doi:10.1038/s41388-024-03254-3
Identification of novel germline mutations in FUT7 and EXT1 linked with hereditary multiple exostosesSynthesis of portimines reveals the basis of their anti-cancer activity
Nature, Published online: 20 September 2023; doi:10.1038/s41586-023-06535-1
A scalable total synthesis of portimines enables structural reassignment of portimine B and in-depth functional evaluation of portimine A, revealing that portimine A induces translation inhibition selectively in human cancer cells and is efficacious in vivo tumour-clearance models.Scientific discovery in the age of artificial intelligence
Nature, Published online: 02 August 2023; doi:10.1038/s41586-023-06221-2
The advances in artificial intelligence over the past decade are examined, with a discussion on how artificial intelligence systems can aid the scientific process and the central issues that remain despite advances.Author Correction: An engineered influenza virus to deliver antigens for lung cancer vaccination
Nature Biotechnology, Published online: 13 July 2023; doi:10.1038/s41587-023-01884-8
Author Correction: An engineered influenza virus to deliver antigens for lung cancer vaccinationAn engineered influenza virus to deliver antigens for lung cancer vaccination
Nature Biotechnology, Published online: 25 May 2023; doi:10.1038/s41587-023-01796-7
A cancer vaccine is delivered to the lung by an engineered attenuated influenza virus.