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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.
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.
基于正交质谱的N-糖组谱揭示哈夫病潜在病原学 Article
刘思, 刘圆圆, 林佳静, 刘笔锋, 何振宇, 吴晓旻, 刘欣
《工程（英文）》 2023年 第26卷 第7期 页码 63-73 doi: 10.1016/j.eng.2022.09.012
结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性 Article
Di Wang, Katarina Madunić , Tao Zhang, Guinevere S.M. Lageveen-Kammeijer, Manfred Wuhrer
《工程（英文）》 2023年 第26卷 第7期 页码 32-43 doi: 10.1016/j.eng.2022.08.016
Aberrant glycosylation is considered to be a hallmark of colorectal cancer (CRC), as demonstrated by various studies. While the N-glycosylation of cell lines and serum has been widely examined, the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures. To overcome these obstacles, we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous, stromal, and healthy mucosa cells. N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatography-electrospray ionization tandem mass spectrometry, enabling the differentiation and structural characterization of isomeric species. In total, 116 N-glycans were identified that showed profound differences in expression among cancer, stroma, and normal mucosa. In comparison with healthy mucosa, the cancer cells showed an increase in α2-6 sialylation and monoantennary N-glycans, as well as a decrease in bisected N-glycans. Moreover, specific sialylated and (sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers. In comparison with cancer, the stroma showed lower levels of oligomannosidic and monoantennary N-glycans, LewisA/X epitopes, and sulfation, as well as increased expression of (core-)fucosylation and α2-3 sialylation. Our study reveals the distinct N-glycomic profiles of different cell types in CRC tumor and control tissues, proving the necessity of their separate analysis for the discovery of cancer-associated glycans.
关键词： 结直肠癌 肿瘤 多孔石墨化碳液相色谱-质谱 N-糖组 抗体反应
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
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
随着高通量测序技术的发展与完善，单组学研究日趋成熟，而整合多组学数据研究植物生长发育的工作方兴未艾。多组学研究在作物重要基因挖掘、全基因组关联分析、基因表达调控网络构建、作物全基因组选择、系统生物学研究等方面发挥着日益重要的作用。
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
结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性
Di Wang, Katarina Madunić , Tao Zhang, Guinevere S.M. Lageveen-Kammeijer, Manfred Wuhrer
期刊论文
分子标记的开发和系统发育基因组学实操班
2019年06月27日
会议信息
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
第五届国际农业基因组学大会
2019年11月21日
会议信息
第七届国际昆虫生理生化与分子生物学论坛及第四届国际昆虫基因组学大会
2019年07月02日
会议信息
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