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代谢组扩展生物学的“旁中心法则”——对理解基因组学-糖组学-代谢组学-表观基因组学互作的意义
Albert Stuart Reece
《工程(英文)》 2023年 第26卷 第7期 页码 16-16 doi: 10.1016/j.eng.2022.07.011
The central dogma of biology holds that the transcription of DNA into RNA and the translation of RNA into proteins forms the primary axis of biological activity [1]. Following major advances in the description of the complex glycan and lipid chains that are added onto these basic building blocks, the glycome and lipidome have recently been added to this doctrine as an exciting new extension named the ‘‘paracentral dogma” [2]. However, it has been pointed out that biological systems can include many layers, which are described in modern omics technology platforms relating to both cell-intrinsic and cell-extrinsic layers of control, including metabolomic, microbiomic, immunological, epigenomic, epitranscriptomic, proteomic and phosphoproteomic layers [3].
It is well known that stem and progenitor cells have a metabolism that is based on glycolysis and glutaminolysis [4]. Although this provides less energy to the cell than oxidative phosphorylation, it suffices for these cells’ needs, since such cells are generally relatively quiescent and normally suppress energy-intensive processes such as genome duplication and transcription. Moreover, it has been shown that the high intracellular lactate levels involved in such states not only inhibits the key gatekeeper enzymes of oxidative phosphorylation (i.e., pyruvate dehydrogenase and carnitine palmitoyl acyltransferase) but also actually covalently modifies them by lactylation in order to maintain this inhibited metabolic–epigenomic state [5]. In addition, intermediate metabolism and nutrients are the source of the very extensive library of post-translational modifications to DNA, RNA, and proteins, as well as supplying cellular energy for many of the required reactions. Hence, the metabolic state locks in and reinforces the epigenomic state, and the metabolome and epigenome thereby play mutually reinforcing roles. This self-reinforcing coordination explains why it is so difficult to generate induced pluripotent cells and is a contributory explanation for why the described protocols typically have such low cellular yields.
These concepts become even more important when it is considered that cancer cells are de-differentiated, similarly rely on glycolysis and glutaminolysis, and are similarly metabolically–epigenomically–genomically synchronized. The disruption of this metabolic system is a key focus of mechanistic cancer research.
These important considerations imply that the descriptive and predictive power of the newly described ‘‘paracentral dogma” of biology may be usefully and meaningfully extended by including the metabolome, along with the genome, transcriptome, proteome, glycome, and lipidome, to describe cell-intrinsic regulation—not only in terms of another omics analytical layer but also as a fully predictive and interactive partner in the symphonic-like multilayer coordination that evidently comprises cellular regulatory layering.
功能代谢组学揭示黄芪多糖通过2-羟基丁酸改善肥胖小鼠的脂质代谢 Article
李冰冰, 洪颖, 顾彧, 叶圣洁, 胡凯莉, 姚建, 丁侃, 赵爱华, 贾伟, 李后开
《工程(英文)》 2022年 第9卷 第2期 页码 111-122 doi: 10.1016/j.eng.2020.05.023
中医方证代谢组学——中药效应评价的有效途径 Review
张爱华, 孙晖, 闫广利, 韩莹, 赵琦琦, 王喜军
《工程(英文)》 2019年 第5卷 第1期 页码 60-68 doi: 10.1016/j.eng.2018.11.008
有效性评价是发现中药药效物质基础、先导化合物和质量标志物的重要前提,因此急需建立一种生物学语言,将中药有效性科学地表达出来,进一步凸显中医药的实用价值。我们以证候和方剂为研究对象,建立了科学评价中药有效性的创新方法学体系——中医方证代谢组学。它将中药血清药物化学理论与代谢组学技术有机整合,在解决证候生物标记物的基础上,建立方剂药效生物评价体系,发现并确认中药药效物质基础。该策略为提高中医理论和临床实践的科学价值提供了有力支持。本文概述了中医方证代谢组学的研究策略,利用该方法揭示临床常见中医证候生物标记物及开展相关方剂的有效性评价研究,着重阐述了中药药效物质基础及质量标记物的发现。
深古菌门的核心代谢功能和热环境起源 Article
冯晓远, 王寅炤, Rahul Zubi, 王风平
《工程(英文)》 2019年 第5卷 第3期 页码 498-504 doi: 10.1016/j.eng.2019.01.011
肝脏移植术后糖尿病患者肠道微生物组的变化 Article
凌琪, 韩玉秋, 马越, 王晓森, 朱铮, 王靖宇, 曹佳莹, 林笑含, 王军, 王保红
《工程(英文)》 2023年 第31卷 第12期 页码 98-111 doi: 10.1016/j.eng.2023.09.006
多组学联用揭示花粉过敏基于肠道菌的新机制 Article
韩珮, 李丽莎, 王子熹, 锡琳, 于航, 丛林, 张正威, 符洁, 彭冉, 潘利斌, 马殊荣, 王学艳, 王洪田, 王向东, 王琰, 孙劲旅, 蒋建东
《工程(英文)》 2022年 第15卷 第8期 页码 115-125 doi: 10.1016/j.eng.2021.03.013
人类蛋白质N-糖基化的十二年全基因组关联研究 Review
Anna Timoshchuk, Sodbo Sharapov, Yurii S. Aulchenko
《工程(英文)》 2023年 第26卷 第7期 页码 17-31 doi: 10.1016/j.eng.2023.03.013
Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains, or glycans. Glycosylation influences the physical and chemical properties of proteins, as well as their biological functions. Unsurprisingly, alterations in protein glycosylation have been implicated in a growing number of human diseases, and glycans are increasingly being considered as potential therapeutic targets, an essential part of therapeutics, and biomarkers. Although glycosylation pathways are biochemically well-studied, little is known about the networks of genes that guide the cell- and tissue-specific regulation of these biochemical reactions in humans in vivo. The lack of a detailed understanding of the mechanisms regulating glycome variation and linking the glycome to human health and disease is slowing progress in clinical applications of human glycobiology. Two of the tools that can provide much sought-after knowledge of human in vivo glycobiology are human genetics and genomics, which offer a powerful data-driven agnostic approach for dissecting the biology of complex traits. This review summarizes the current state of human populational glycogenomics. In Section 1, we provide a brief overview of the N-glycan's structural organization, and in Section 2, we give a description of the major blood plasma glycoproteins. Next, in Section 3, we summarize, systemize, and generalize the results from current N-glycosylation genome-wide association studies (GWASs) that provide novel knowledge of the genetic regulation of the populational variation of glycosylation. Until now, such studies have been limited to an analysis of the human blood plasma N-glycome and the N-glycosylation of immunoglobulin G and transferrin. While these three glycomes make up a rather limited set compared with the enormous multitude of glycomes of different tissues and glycoproteins, the study of these three does allow for powerful analysis and generalization. Finally, in Section 4, we turn to genes in the established loci, paying particular attention to genes with strong support in Section 5. At the end of the review, in Sections 6 and 7, we describe special cases of interest in light of new discoveries, focusing on possible mechanisms of action and biological targets of genetic variation that have been implicated in human protein N-glycosylation.
血浆代谢组学结合超微弱发光表征早期2型糖尿病的中医证型 Article
何敏, 孙濛濛, Slavik Koval, Roeland Van Wijk, Thomas Hankemeier, Jan Van der Greef, Eduard P.A. Van Wijk, 王梅
《工程(英文)》 2019年 第5卷 第5期 页码 916-923 doi: 10.1016/j.eng.2019.03.011
徐健, 马波, 苏晓泉, 黄适, 徐欣, 周学东, 黄巍, Rob Knight
《工程(英文)》 2017年 第3卷 第1期 页码 66-70 doi: 10.1016/J.ENG.2017.01.020
方法学创新一直是微生物组学研究的核心驱动力。我们认为在未来五到十年,微生物组的方法学体系在研究理念与技术平台方面将发生三大变革:①从监测菌群“结构”变化向监测菌群“功能/状态”变化的变革;②从细胞&我们相信中国微生物组计划应把握住当前这一重要机遇,通过在微生物组分析方法学前沿开展富有雄心、远见、创意与竞争力的交叉合作研究,为国际微生物组计划贡献一系列“中国制造”的新方法、新工具和新仪器
时间序列多组学整合分析揭示原代肝细胞体外培养去分化过程伴随非降解性泛素化修饰的增加 Article
姜正一, 孙泽宇, 欧阳晓希, 赵亚磊, 周梦豪, 王保红, 李启睿, 范林骁, 张赛男, 李兰娟
《工程(英文)》 2020年 第6卷 第11期 页码 1302-1314 doi: 10.1016/j.eng.2020.02.011
目前,原代肝细胞(PHC)在各个研究领域被广泛使用,但是由于在体外培养过程中肝细胞特异性功能的迅速退化(即去分化),严重限制了它的应用范围尽管学者已经对PHC的转录调控和全细胞蛋白质组(WCP)进行了广泛研究,但只有为数不多的研究考虑了蛋白质翻译后修饰(PTM)在这一过程中的作用。为了揭示引起PHC去分化的潜在机制,我们收集了在体外培养0 h、6 h、12 h、24 h和48 h的大鼠原代肝细胞样本,对各个时间点细胞样本的转录组、WCP、泛素化蛋白质组和磷酸化蛋白质组进行了定量分析泛素化修饰组和对应的WCP联合分析表明,PHC去分化伴随着非降解性K27泛素化修饰位点的增加。对差异表达的磷酸化修饰蛋白进行功能富集分析,表明该过程中有铁死亡参与。
温维亮,郭新宇 ,张颖,顾生浩,赵春江
《中国工程科学》 2023年 第25卷 第4期 页码 227-238 doi: 10.15302/J-SSCAE-2023.04.015
利用集成自动化平台装备和信息化技术手段,获取多尺度、多生境、多源异构的作物表型组大数据,将极大地促进作物功能基因组学、数字育种、智慧栽培的研究进程综合利用遗传学、基因组学、分子生物学等技术手段,挖掘株型、穗型、种子大小等产量性状,蛋白质、油分、硬度等品质性状,养分吸收、转运、代谢等养分高效利用性状的关键调控基因,阐明高产、优质、高效协同改良的分子调控网络2020年,华中农业大学成功整合了来自同一玉米群体的基因组、转录组、表型组、代谢组、表观基因组、遗传变异、遗传定位结果等多组学数据,构建了玉米定制化多组学数据库(ZEAMAP)[学数据,差异表达基因识别、复杂表型的转录因子识别或代谢物富集等遗传调控研究进展迅速,代表性工作有:利用显微电子计算机断层扫描(CT)表型技术结合全基因组关联分析(GWAS),鉴定到调控维管束数目作物表型解析的研究重点是增加可观测、可定量化、具有明确生物学含义的作物表型性状数量,提高可定量化作物表型解析的精度和效率;针对不同作物的形态结构和生理生态功能,研发相关算法开展定制化的表型解析。
新孢子虫病——分子流行病学及发病机制综述 Review
Asis Khan, Jahangheer S. Shaik, Patricia Sikorski, Jitender P. Dubey, Michael E. Grigg
《工程(英文)》 2020年 第6卷 第1期 页码 10-19 doi: 10.1016/j.eng.2019.02.010
通过原位观察揭示人体肠道微生物组的重建和动态变化 Article
刘小林, 戴敏, Yue Ma, 赵娜, Ziyu Wang, Ying Yu, Yakun Xu, Huijie Zhang, Liyuan Xiang, He Tian, 税光厚, 张发明, 王军
《工程(英文)》 2022年 第15卷 第8期 页码 89-101 doi: 10.1016/j.eng.2021.03.015
人体肠道微生物组主要通过使用粪便样本进行研究,这种做法已经得到了关于胃肠道微生物群落的组成和功能的重要知识。在我们的研究中,我们利用结肠途径经内镜肠内导管(一种最初为粪便微生物群移植开发的技术)每天两次对回盲部微生物组进行采样;然后对这些样品进行宏基因组和宏转录组学分析。在5 名志愿者中分析的回盲部和粪便微生物组被发现在宏基因组分析中相似,但它们的活性基因(宏转录组)被发现高度不同。白天和夜间对回盲部微生物组的采样显示,在一系列细菌种类和功能途径中存在昼夜节律,特别是与短链脂肪酸产生相关的细菌,如痤疮丙酸杆菌和辅酶A生物合成II。粪便和尿液样本中的代谢组学分析反映出了肠道微生物组的扰动和恢复,表明肠道微生物组对参与宿主健康的诸多关键代谢物的重要贡献。
标题 作者 时间 类型 操作
多组学联用揭示花粉过敏基于肠道菌的新机制
韩珮, 李丽莎, 王子熹, 锡琳, 于航, 丛林, 张正威, 符洁, 彭冉, 潘利斌, 马殊荣, 王学艳, 王洪田, 王向东, 王琰, 孙劲旅, 蒋建东
期刊论文
血浆代谢组学结合超微弱发光表征早期2型糖尿病的中医证型
何敏, 孙濛濛, Slavik Koval, Roeland Van Wijk, Thomas Hankemeier, Jan Van der Greef, Eduard P.A. Van Wijk, 王梅
期刊论文
新孢子虫病——分子流行病学及发病机制综述
Asis Khan, Jahangheer S. Shaik, Patricia Sikorski, Jitender P. Dubey, Michael E. Grigg
期刊论文