Real-world clinical utility of comprehensive genomic profiling in advanced solid tumors - Nature

AcknowledgementsThe authors thank the Yale Department of Pathology and Yale Pathology Tissue Services for technical and tissue-related support. FundingThe research is supported by Maximizing Investigators Research Award (MIRA) for Early-Stage Investigators 1R35GM150838 (to Y. L.). The research is also supported, in part, by Grant #IRG-21-132-60-IRG from the American Cancer Society. We also acknowledge the support of Leslie H. Warner Postdoctoral Fellowship to D. W. Author informationAuthor notesThese authors contributed equally: Bo Tao, Deguang Song, Mingze Dong, Gaocai Li. Authors and AffiliationsDepartment of Pathology, Yale School of Medicine, New Haven, CT, USABo Tao, Mingze Dong, Gaocai Li, Shenjie Wang, Dejiang Wang, Xiangjun Di, Fu Gao, Liyun Lin, Xiaohui Yu, Junyi Xu, Mo Liu, Mariana Kelley, Anthony Y. Feng, Yu Jin, Yuval Kluger & Yang LiuDepartment of Neurology, Yale School of Medicine, New Haven, CT, USABo Tao, Gaocai Li, Shenjie Wang, Dejiang Wang, Xiangjun Di, Fu Gao, Liyun Lin, Xiaohui Yu, Mariana Kelley & Yang LiuDepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USADeguang Song & Noah W.

AbstractBackgroundMultiple sclerosis (MS) is characterized by immune dysregulation, yet the molecular alterations present at disease onset remain incompletely understood. We sought to characterize immune cell-specific proteomic changes before treatment initiation in early MS and assess their impact on immune cell communication. MethodsWe performed high-resolution proteomic profiling of four major peripheral immune cell populations, CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes, from newly diagnosed, treatment-naïve individuals with MS and matched healthy controls. Differential protein expression, pathway enrichment, genetic overlap, and ligand–receptor analyses were performed. ResultsAll four immune cell populations exhibit distinct proteomic alterations that discriminate individuals with MS from healthy controls. Differentially expressed proteins are enriched in pathways related to coagulation, antigen processing, vesicle trafficking, oxidative phosphorylation, and cellular stress responses. Disease-associated proteins overlap with established MS susceptibility genes, with the strongest enrichments observed in CD14⁺ monocytes and CD19⁺ B cells.

New details are emerging about the parent who fatally shot the 16-year-old shooter who killed three children and a teacher in Oregon last week. In a 2018 Facebook post, Kaylub Giamanco, the 36-year-old carpenter who shot and killed the shooter, said he had gone through “military shooting drills” with veterans who fought in Iraq. In addition to the four people killed, the shooting in Bend left a seven-year old student in hospital, receiving “lifesaving care”, and 54-year-old teacher Becky Drury with serious but non-life-threatening injuries. The shooter, 16-year-old Griffin J John II, first opened fire outside the school with a shotgun, aiming at a driver who tried to confront him. He then shot through locked doors, forcing entry on to the elementary school campus. Giamanco, who has two daughters at the school, was driving back from his lunch break when he heard gunfire coming from the campus. He parked his car near the building, took a legally registered 40-caliber pistol from his vehicle and raced inside, according to Bend police. Before his arrival, a teacher threw a cellphone at the assailant and tackled him, and tried to wrestle the gun from his hands.