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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
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.
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.
陈松林,徐文腾,陈张帆
《中国工程科学》 2019年 第21卷 第6期 页码 39-47 doi: 10.15302/J-SSCAE-2019.06.007
本文主要从基因组和转录组层面分析了极地动物基因资源的研究现状,梳理了本领域研究中存在的问题,并提出了未来发展战略。极地动物基因组测序起步较晚,迄今只完成了 13种极地动物的全基因组测序。在转录组研究方面,人们对极地的 31个物种进行了转录组测序,并在以下四个方向重点开展了研究:环境适应性研究;污染物应激反应的分子机制研究;不同发育阶段或不同组织中的转录组分析;功能基因挖掘。
关键词: 极地动物 基因组,转录组,基因资源
基于转录组学及多尺度生物测定多模态鉴定宣肺败毒方抑制巨噬细胞免疫反应的活性成分 Article
赵璐, 刘豪, 王迎超, 王书芳, 荀得金, 王毅, 程翼宇, 张伯礼
《工程(英文)》 2023年 第20卷 第1期 页码 63-76 doi: 10.1016/j.eng.2021.09.007
大鼠脊髓发育过程中时序转录组的发育时间模式和分子网络特征 Article
杨建, 赵莉莉, 易晟, 丁斐, 杨宇民, 刘炎, 王勇军, 刘梅, 薛成斌, 许莲, 龚蕾蕾, 王星辉, 张愉, 于彬, 明国丽, 顾晓松
《工程(英文)》 2021年 第7卷 第11期 页码 1592-1602 doi: 10.1016/j.eng.2021.10.001
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。两种微生物组在泻药暴露后都受到干扰;随着时间的推移,它们表现出与治疗前状态的差异减少,从而证明了作为肠道微生物组的先天特性——恢复力,尽管它们在我们的观察时间窗口内没有完全恢复。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。
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。
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
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
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
标题 作者 时间 类型 操作
大鼠脊髓发育过程中时序转录组的发育时间模式和分子网络特征
杨建, 赵莉莉, 易晟, 丁斐, 杨宇民, 刘炎, 王勇军, 刘梅, 薛成斌, 许莲, 龚蕾蕾, 王星辉, 张愉, 于彬, 明国丽, 顾晓松
期刊论文
通过原位观察揭示人体肠道微生物组的重建和动态变化
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
期刊论文