Suppr超能文献

时光飞逝:一种用于果蝇头部的单链核糖核酸测序衰老时钟揭示了性别差异衰老现象。

TimeFlies: an snRNA-seq aging clock for the fruit fly head sheds light on sex-biased aging.

作者信息

Tennant Nikolai, Pavuluri Ananya, O'Connor-Giles Kate, Singh Gunjan, Larschan Erica, Singh Ritambhara

机构信息

Data Science Institute, Brown University, Providence, RI, USA.

Center for Computational Molecular Biology, Brown University, Providence, RI, USA.

出版信息

bioRxiv. 2025 Jan 25:2024.11.25.625273. doi: 10.1101/2024.11.25.625273.

Abstract

Although multiple high-performing epigenetic aging clocks exist, few are based directly on gene expression. Such transcriptomic aging clocks allow us to extract age-associated genes directly. However, most existing transcriptomic clocks model a subset of genes and are limited in their ability to predict novel biomarkers. With the growing popularity of single-cell sequencing, there is a need for robust single-cell transcriptomic aging clocks. Moreover, clocks have yet to be applied to investigate the elusive phenomenon of sex differences in aging. We introduce TimeFlies, a pan-cell-type scRNA-seq aging clock for the head. TimeFlies uses deep learning to classify the donor age of cells based on genome-wide gene expression profiles. Using explainability methods, we identified key marker genes contributing to the classification, with lncRNAs showing up as highly enriched among predicted biomarkers. The top biomarker gene across cell types is lncRNA:, a regulator of X chromosome dosage compensation, a pathway previously identified as a top biomarker of aging in the mouse brain. We validated this finding experimentally, showing a decrease in survival probability in the absence of roX1 . Furthermore, we trained sex-specific TimeFlies clocks and noted significant differences in model predictions and explanations between male and female clocks, suggesting that different pathways drive aging in males and females.

摘要

尽管存在多个高性能的表观遗传衰老时钟,但基于基因表达直接构建的却很少。这种转录组衰老时钟使我们能够直接提取与年龄相关的基因。然而,大多数现有的转录组时钟仅对一部分基因进行建模,在预测新生物标志物方面能力有限。随着单细胞测序越来越受欢迎,需要强大的单细胞转录组衰老时钟。此外,时钟尚未被用于研究衰老中难以捉摸的性别差异现象。我们推出了TimeFlies,一种用于头部的全细胞类型scRNA-seq衰老时钟。TimeFlies利用深度学习根据全基因组基因表达谱对细胞的供体年龄进行分类。通过可解释性方法,我们确定了有助于分类的关键标记基因,lncRNA在预测的生物标志物中高度富集。跨细胞类型的顶级生物标志物基因是lncRNA:,它是X染色体剂量补偿的调节因子,该途径先前被确定为小鼠大脑衰老的顶级生物标志物。我们通过实验验证了这一发现,表明在没有roX1的情况下存活概率降低。此外,我们训练了性别特异性的TimeFlies时钟,并注意到雄性和雌性时钟在模型预测和解释上存在显著差异,这表明不同的途径驱动着雄性和雌性的衰老。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3db/11785003/dde345a2fbae/nihpp-2024.11.25.625273v3-f0002.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验