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基因组解析宏基因组学:微生物组医学的游戏规则改变者

Genome-resolved metagenomics: a game changer for microbiome medicine

Nature 等信源发布 2024-07-01 08:56

可切换为仅中文


AbstractRecent substantial evidence implicating commensal bacteria in human diseases has given rise to a new domain in biomedical research: microbiome medicine. This emerging field aims to understand and leverage the human microbiota and derivative molecules for disease prevention and treatment. Despite the complex and hierarchical organization of this ecosystem, most research over the years has relied on 16S amplicon sequencing, a legacy of bacterial phylogeny and taxonomy.

摘要最近有大量证据表明共生细菌与人类疾病有关,这引发了生物医学研究的一个新领域:微生物组医学。这一新兴领域旨在了解和利用人类微生物群和衍生分子进行疾病预防和治疗。尽管这个生态系统的组织复杂且层次分明,但多年来大多数研究都依赖于16S扩增子测序,这是细菌系统发育和分类学的遗产。

Although advanced sequencing technologies have enabled cost-effective analysis of entire microbiota, translating the relatively short nucleotide information into the functional and taxonomic organization of the microbiome has posed challenges until recently. In the last decade, genome-resolved metagenomics, which aims to reconstruct microbial genomes directly from whole-metagenome sequencing data, has made significant strides and continues to unveil the mysteries of various human-associated microbial communities.

尽管先进的测序技术已经能够对整个微生物群进行具有成本效益的分析,但将相对较短的核苷酸信息转化为微生物组的功能和分类学组织直到最近才提出挑战。。

There has been a rapid increase in the volume of whole metagenome sequencing data and in the compilation of novel metagenome-assembled genomes and protein sequences in public depositories. This review provides an overview of the capabilities and methods of genome-resolved metagenomics for studying the human microbiome, with a focus on investigating the prokaryotic microbiota of the human gut.

全宏基因组测序数据的数量以及公共保存库中新的宏基因组组装基因组和蛋白质序列的汇编迅速增加。本综述概述了基因组解析宏基因组学研究人类微生物组的能力和方法,重点是研究人类肠道的原核微生物群。

Just as decoding the human genome and its variations marked the beginning of the genomic medicine era, unraveling the genomes of commensal microbes and their sequence variations is ushering us into the era of microbiome medicine. Genome-resolved metagenomics stands as a pivotal tool in this transition and can accelerate our journey toward achieving these scientific and medical milestones..

正如解码人类基因组及其变异标志着基因组医学时代的开始一样,解开共生微生物的基因组及其序列变异将我们带入微生物组医学时代。基因组解析宏基因组学是这一转变的关键工具,可以加速我们实现这些科学和医学里程碑的旅程。。

IntroductionThe human body is home to a multitude of symbiotic microbial cells that outnumber the host’s own cells and exert a significant influence on human physiology. As evidence regarding the role of commensal microbes in human diseases has accumulated, microbiome medicine has emerged as a new field in biomedical research.

引言人体是大量共生微生物细胞的家园,其数量超过宿主自身的细胞,并对人体生理产生重大影响。随着共生微生物在人类疾病中作用的证据积累,微生物组医学已成为生物医学研究的一个新领域。

This field seeks to harness human microbiota and derived molecules for the prevention and treatment of diseases. Achieving this goal requires a comprehensive understanding of the taxonomic and functional organization of the human microbiome.Historically, microbial community research has been a domain within microbial ecology that was initially focused on environmental microbes.

该领域旨在利用人类微生物群和衍生分子来预防和治疗疾病。实现这一目标需要全面了解人类微生物组的分类学和功能组织。从历史上看,微生物群落研究一直是微生物生态学中的一个领域,最初专注于环境微生物。

However, the discovery of vast microbial communities within the human body has expanded the scope of this field. For many years, human microbiome research has adopted methodologies based on bacterial phylogeny and taxonomy, particularly 16S rRNA gene sequence analysis1, which is adequate for revealing differences in taxonomic composition between diseased microbiomes and their healthy counterparts.

然而,人体内大量微生物群落的发现扩大了这一领域的范围。多年来,人类微生物组研究采用了基于细菌系统发育和分类学的方法,特别是16S rRNA基因序列分析1,这足以揭示患病微生物组与其健康对应物之间分类学组成的差异。

However, the limited taxonomic resolution of 16S rRNA sequences2 and their inherent inability to perform functional analysis pose obstacles to further advancements, including identifying the functional elements of the microbiome that directly influence host physiology. This situation is reminiscent of human genetics prior to the availability of the human reference genome.

然而,16S rRNA序列2的有限分类学分辨率及其固有的无法进行功能分析对进一步的进展构成了障碍,包括鉴定直接影响宿主生理学的微生物组的功能元件。这种情况让人想起人类参考基因组可用之前的人类遗传学。

The absence of a comprehensive human genome map meant that the search for disease genes was based on sparse genomic landmarks, leading to the identification of only broad chromosomal regions associated with diseases. This approach often requires years of subsequent studies to precisely locate the genes responsibl.

缺乏全面的人类基因组图谱意味着对疾病基因的搜索是基于稀疏的基因组标志,导致仅鉴定与疾病相关的广泛染色体区域。这种方法通常需要多年的后续研究才能精确定位负责的基因。

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Download referencesAcknowledgementsThis research was supported by the Korea Health Technology R&D Project, Korea Health Industry Development Institute (KHIDI), Ministry of Health & Welfare, Republic of Korea grant HI19C1344 (NY). P.B. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK125382).

下载参考文献致谢本研究得到了韩国卫生技术研发项目,韩国卫生与福利部韩国卫生产业发展研究所(KHIDI)的支持,韩国HI19C1344(NY)。P、 B.得到了国家糖尿病、消化和肾脏疾病研究所(R01 DK125382)的支持。

The funding agencies had no role in the design and preparation of this manuscript.Author informationAuthors and AffiliationsDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of KoreaNayeon Kim, Junyeong Ma, Wonjong Kim, Jungyeon Kim & Insuk LeeDepartment of Molecular Microbiology and Immunology, Brown University, Providence, RI, 02912, USAPeter BelenkyPOSTECH Biotech Center, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of KoreaInsuk LeeAuthorsNayeon KimView author publicationsYou can also search for this author in.

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