Novel biological insights by utilizing mitochondrial genome information from HuBMAP resources

项目总结 尽管典型的scRNA-seq或scatac-seq数据包含映射到线粒体DNA的5-25%的读数 (MtDNA)基因组，这种mtDNA定位的读数在下游分析过程中经常被过滤或忽略。这个 线粒体产生了超过90%的细胞能量，是健康和疾病的核心。线粒体DNA突变 直接导致线粒体疾病。此外，随机的体细胞mtDNA突变随着年龄和年龄的增加而积累 与一系列与衰老有关的疾病有关，如免疫紊乱、心血管疾病 和神经退化。然而，关于特定mtdna变种的积累是否 在不同的细胞类型、器官、年龄、性别和种族之间，衰老发生的速度是相同的。这样的洞察力 将大大提高我们对线粒体DNA突变如何导致各种人类疾病的理解。 因此，单细胞生物学领域的重大知识空白包括缺乏强大的mtdna。 分析工具以及如何利用在不断增长的数据集中经常被忽视的丰富的mtDNA信息来 获得新的生物学见解。我们建议通过以下方式解决这些知识差距：(1)开发健壮的mtdna 与HuBMAP门户集成的分析工作流程和工具；(2)系统分析来自单个数据库的mtDNA 由HuBMAP和其他资源生成的细胞数据集；(3)确定人类是否以及如何流行 线粒体DNA变异会影响线粒体和细胞功能。

PROJECT SUMMARY Although typical scRNA-seq or scATAC-seq data contain 5-25% of reads that map to the mitochondrial DNA (mtDNA) genome, such mtDNA mapped reads are often filtered out or ignored during downstream analysis. The mitochondria generate over 90% of the cellular energy and are central to health and disease. mtDNA mutations directly cause mitochondrial disease. In addition, random somatic mtDNA mutations accumulate with age and are associated with a broad range of aging-related diseases such as immune disorders, cardiovascular disease and neurodegeneration. However, little is understood about whether accumulation of specific mtDNA variants during aging occurs at the same rate across different cell types, organs, age, gender and race. Such insights would substantially improve our understanding of how mtDNA mutations contribute to various human diseases. Accordingly, significant gaps of knowledge in the single-cell biology field include the lack of robust mtDNA analysis tools and how to utilize the rich mtDNA information often neglected in the ever-increasing datasets to obtain new biological insights. We propose to address these knowledge gaps by: (1) develop robust mtDNA analysis workflows and tools integrated with the HuBMAP Portal; (2) systemically analyze mtDNA from single- cell datasets generated by HuBMAP and other resources; (3) determine whether and how prevalent human mtDNA variants impact mitochondrial and cellular function.