临床相关骨质疏松症亚型的多模式分子决定因素。

IF 13 1区 生物学 Q1 CELL BIOLOGY
Chunchun Yuan, Xiang-Tian Yu, Jing Wang, Bing Shu, Xiao-Yun Wang, Chen Huang, Xia Lv, Qian-Qian Peng, Wen-Hao Qi, Jing Zhang, Yan Zheng, Si-Jia Wang, Qian-Qian Liang, Qi Shi, Ting Li, He Huang, Zhen-Dong Mei, Hai-Tao Zhang, Hong-Bin Xu, Jiarui Cui, Hongyu Wang, Hong Zhang, Bin-Hao Shi, Pan Sun, Hui Zhang, Zhao-Long Ma, Yuan Feng, Luonan Chen, Tao Zeng, De-Zhi Tang, Yong-Jun Wang
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引用次数: 0

摘要

由于全球人口迅速老龄化,骨质疏松症及其相关的骨折风险已成为一个普遍的公共卫生问题。然而,骨质疏松症具有很强的异质性,现有的标准诊断方法不足以准确识别所有有骨质疏松性骨折风险的患者并指导治疗。在这里,我们构建了迄今为止最大的骨质疏松症队列(366 名参与者在三个时间点的纵向数据)的首个前瞻性多组学图谱,还实施了一个可解释的数据密集型分析框架(DLSF:深度潜空间融合),用于基于多模态方法的全基因模型,该方法可以捕获多模态分子特征(M3S),将其作为隐藏基因型的明确功能表征。因此,通过 DLSF,我们发现了中国骨质疏松症人群中的两个亚型,并确定了相应的分子表型,即临床干预相关亚型(CISs),在这些亚型中,2 年随访样本中的骨矿物质密度对钙补充剂有益处。与这些分子表型相关的许多 snpGenes 揭示了骨质疏松症潜在的多种候选生物机制,骨质疏松症及其亚型的 xQTL 偏好表明了对不同生物领域的全方位影响。最后,根据 4 年的随访数据发现,这两种亚型与既往骨折的相关性不同,骨折风险也不同。因此,在临床应用中,M3S 可以帮助我们进一步开发出更好的骨质疏松症诊断和治疗策略,并确定一种新的骨折预测综合指数,这在一个独立队列(166 名参与者)中得到了显著验证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

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来源期刊
Cell Discovery
Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍: Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.
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