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Sepsis biomarkers: an omics perspective

null

《医学前沿（英文）》 2014年第8卷第1期页码 58-67 doi: 10.1007/s11684-014-0318-2

摘要：

Sepsis is a common cause of death in hospitalized patients worldwide. The early detection of sepsis remains a great challenge for clinicians, and delayed diagnosis frequently undermines treatment efforts, thereby contributing to high mortality. Omics technologies allow high-throughput screening of sepsis biomarkers. This review describes currently available and novel sepsis biomarkers in the context of genomics, transcriptomics, proteomics, and metabolomics. The combination of these technologies can help refine the diagnosis of sepsis. This review paper serves as a reference for future studies that employ an integrated, multi-omics approach to disease identification.

关键词： sepsis biomarker genomics transcriptomics proteomics metabolomics

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Deciphering the pharmacological mechanism of Guan-Jie-Kang in treating rat adjuvant-induced arthritis using omics

Hudan Pan, Yanfang Zheng, Zhongqiu Liu, Zhongwen Yuan, Rutong Ren, Hua Zhou, Ying Xie, Liang Liu

《医学前沿（英文）》 2019年第13卷第5期页码 564-574 doi: 10.1007/s11684-018-0676-2

摘要： Traditional Chinese medicine (TCM) formulas have attracted increasing attention worldwide in the past few years for treating complex disease including rheumatoid arthritis. However, their mechanisms are complex and remain unclear. Guan-Jie-Kang (GJK), a prescription modified from “Wu Tou Decoction,” was found to significantly relieve arthritis symptoms in rats with adjuvant-induced arthritis after 30-day treatment, especially in the 24 g/kg/day group. By analyzing 1749 targets related to 358 compounds in the five herbs of GJK, we identified the possible anti-arthritis pathways of GJK, including the calcium signaling and metabolic pathways. Bone damage levels were assessed by micro-computed tomography, and greater bone protective effect was observed with GJK treatment than with methotrexate. Receptor activator of nuclear factor κB ligand (RANKL)–RANK signaling, which is related to calcium signaling, was significantly regulated by GJK. Moreover, a target metabolomics assay of serum was conducted; 17 metabolic biomarkers showed significant correlations with treatment. An integrated pathway analysis revealed that pyruvate metabolism, purine metabolism, and glycolysis metabolism were significantly associated with the effects of GJK in arthritis treatment. Thus, this study establishes a new omics analytical method integrated with bioinformatics analysis for elucidating the multi-pathway mechanisms of TCM.

关键词： rheumatoid arthritis traditional Chinese medicine pharmacological mechanism metabolism adjuvant-induced arthritis omics analysis

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Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

《医学前沿（英文）》页码 596-609 doi: 10.1007/s11684-021-0868-z

摘要： Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.

关键词： innate immune checkpoint Siglec10 kidney renal clear cell carcinoma

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Systems understanding of plant–pathogen interactions through genome-wide protein–protein interaction networks

Hong LI,Ziding ZHANG

《农业科学与工程前沿（英文）》 2016年第3卷第2期页码 102-112 doi: 10.15302/J-FASE-2016100

摘要： Plants are frequently affected by pathogen infections. To effectively defend against such infections, two major modes of innate immunity have evolved in plants; pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity. Although the molecular components as well as the corresponding pathways involved in these two processes have been identified, many aspects of the molecular mechanisms of the plant immune system remain elusive. Recently, the rapid development of omics techniques (e.g., genomics, proteomics and transcriptomics) has provided a great opportunity to explore plant–pathogen interactions from a systems perspective and studies on protein–protein interactions (PPIs) between plants and pathogens have been carried out and characterized at the network level. In this review, we introduce experimental and computational identification methods of PPIs, popular PPI network analysis approaches, and existing bioinformatics resources/tools related to PPIs. Then, we focus on reviewing the progress in genome-wide PPI networks related to plant–pathogen interactions, including pathogen-centric PPI networks, plant-centric PPI networks and interspecies PPI networks between plants and pathogens. We anticipate genome-wide PPI network analysis will provide a clearer understanding of plant–pathogen interactions and will offer some new opportunities for crop protection and improvement.

关键词： plant–pathogen interactions systems biology omics plant immunity protein–protein interaction network

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扩大多元回归方法在跨组学研究中的范围 Article

Xiaoxi Hu, Yue Ma, Yakun Xu, Peiyao Zhao, Jun Wang

《工程（英文）》 2021年第7卷第12期页码 1725-1731 doi: 10.1016/j.eng.2020.05.028

摘要：

近年来科技的进步和发展使得高维数据急剧增加，研究人员对合适且有效的多元回归方法的需求也随之增长。许多传统的多元分析方法如主成分分析等已广泛应用于投资分析、图像识别和群体遗传结构分析等研究领域。然而，这些常见的方法存在其局限性，即忽略了响应之间的相关性和变量选择效率低的问题。因此，本文引入了降秩回归方法及其扩展形式——稀疏降秩回归和行稀疏的子空间辅助回归，这些方法有望满足上述需求，从而提高回归模型的可解释性。我们通过开展仿真研究来评估它们的效果，并将它们与其他几种变量选择方法进行比较。对于不同的应用场景，我们也提供了基于预测能力和变量选择精度的选择建议。最后，为了证明这些方法在微生物组研究领域的实用价值，我们将所选择的方法应用于实际种群水平的微生物组数据，结果验证了我们方法的有效性。该方法的扩展形式为未来的组学研究特别是多元回归研究提供了有价值的指导，并为微生物组学及其相关研究领域的新发现奠定了基础。

关键词：多元回归方法降秩回归稀疏性降维变量选择

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促进肝癌致癌活性和细胞代谢的新型介质——miR-516a-3p

芮韬, 张学优, 冯时, 黄海涛, 詹少伟, 谢海洋, 周琳, 郑树森, 凌琪

《工程（英文）》 2022年第16卷第9期页码 162-175 doi: 10.1016/j.eng.2021.07.020

摘要：

肝细胞肝癌是目前最致命的恶性肿瘤之一。根据先前的研究，19号染色体miRNA簇（C19MC）与肝癌患者的肿瘤高负荷和不良预后相关。目前的研究旨在探讨miR-516a-3p在HCC中的作用。miR-516a-3p是一种由C19MC 4个致癌前体miRNA（即miR-516a-1、miR-516a-2、miR-516b-1和miR-516b-2）所共同剪接而成的相同的成熟体miRNA。在肝癌队列中，与瘤旁组织相比，miR-516a-3p在肝癌组织中显著高表达。肿瘤miR-516a-3p的高表达与肝癌高肿瘤负荷相关，可以区分高HCC复发率和死亡率，并独立预测肝癌的不良预后。进一步通过体外实验发现miR-516a-3p增强了肝癌细胞的增殖、迁移和侵袭性，并通过体内实验验证miR-516a-3p促进了肿瘤的增殖和远处转移能力。在肝癌细胞中，miR-516a-3p可以通过外泌体进行递送，并增加受体肝癌细胞的致癌活性。此外，为探索miR-516a-3p致癌的潜在机制，本研究进行了全面的转录组学、蛋白质组学和代谢组学分析。多组学DIABLO分析显示，蛋白质组学和代谢组学数据之间具有密切的相关性和较强的聚类一致性。进一步证实了6种基因的mRNA（即LMBR1、CHST9、RBM3、SLC7A6、PTGFRN和NOL12）是miR-516a-3p的直接靶点，并在miR-516a-3p介导的代谢调节中发挥核心作用。综合多组学和共富集途径分析表明，miR-516a-3p可以调节肝癌细胞的代谢途径，特别是嘌呤代谢和嘧啶代谢。总之，本研究发现，miR-516a-3p可以通过调节细胞代谢和外泌体递送系统影响相邻细胞，促进肝癌细胞的肿瘤恶性进展。因此，miR-516a-3p可能作为肝癌治疗的新分子靶点。

关键词：肝细胞肝癌 miRNA簇外泌体多组学

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Long-term cultivation and meta-omics reveal methylotrophic methanogenesis in hydrocarbon-impacted habitats

Yi-Fan Liu,Jing Chen,Zhong-Lin Liu,Zhao-Wei Hou,Bo Liang,Li-Ying Wang,Lei Zhou,Li-Bin Shou,Dan-Dan Lin,Shi-Zhong Yang,Jin-Feng Liu,Xiao-Lin Wu,Ji-Dong Gu,Bo-Zhong Mu,

《工程（英文）》 doi: 10.1016/j.eng.2021.08.027

摘要： The microbial conversion of alkanes to methane in hydrocarbon-contaminated environments is an intrinsic bioremediation strategy under anoxic conditions. However, the mechanism of microbial methanogenic alkane degradation is currently unclear. Under ten-years of continuous efforts, we obtained a methanogenic n-alkane-degrading (C15–C20) enrichment culture that exhibited sustained improvements in the kinetic properties of methane production. The integrated metagenomic and metatranscriptomic analyses revealed that n-alkanes were mainly attacked by members of Desulfosarcinaceae, Firmicutes, and Synergistetes using the fumarate addition strategy, and were then further degraded in a common effort by Tepidiphilus members. Meanwhile, the abundant members of Anaerolineaceae were mainly responsible for cell debris recycling. However, according to the metatranscriptomic analyses, methane was predicted to be produced mainly via H2-dependent methylotrophic methanogenesis, primarily from necromass-derived trimethylamine mediated by Methanomethyliaceae within the candidate phylum Verstraetearchaeota. These findings reveal that H2-dependent methylotrophic methanogens, as well as methylotrophic methanogens, may play important ecological roles in the carbon cycle of hydrocarbon enriched subsurface ecosystems.Graphical abstractDownload : Download high-res image (42KB)Download : Download full-size image

关键词： Methanogenic hydrocarbon degradation Oily sludge Bioremediation Alkanes

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多组学导向的链霉菌1647产生的奥米克欣的发现——一组抗甲型流感病毒和冠状病毒HCoV-229E的活性类四肽化合物 Article

孙红敏, 李星星, 陈明华, 钟鸣, 李怡华, 王琨, 杜郁, 甄心, 高荣梅, 巫晔翔, 侍媛媛, 余利岩, 车永胜, 李玉环, 蒋建东, 洪斌, 司书毅

《工程（英文）》 2022年第16卷第9期页码 176-186 doi: 10.1016/j.eng.2021.05.010

摘要：

微生物具有产生抗病毒抗生素以保护细胞存活的机制。链霉菌1647是上世纪70年代从中国南方土壤中分离的一株链霉菌，其发酵液显示出优良的抗甲型流感病毒活性，但其抗病毒活性成分始终没有得到有效的分离和结构鉴定。本文综合利用多组学研究策略，从这株链霉菌中成功分离得到抗病毒活性成分。利用antiSMASH（抗生素及次级代谢产物分析软件）分析该菌株的基因组序列信息，发现其中可能含有38个次级代谢产物生物合成基因簇，经过生物活性导向的比较转录组学分析初步锁定三个可能的目标抗病毒活性化合物的生物合成基因簇。通过生物信息学分析及对基因簇36中调节基因和生物合成基因的遗传操作，确定了其为抗病毒活性化合物的生物合成基因簇。对野生株和不同重组菌株发酵产物进行基于生物活性导向的质谱数据分子网络分析，初步确定了抗病毒成分是一组化学结构类似物。最后通过高分辨质谱和二维核磁共振波谱分析，确定了抗病毒活性成分为包括18个含有脲基的类四肽结构，取名为奥米克欣（omicsynin）A1~A6、B1~B6和C1~C6，其中11个（A1、A2、A6、B1~B3、B5、B6、C1、C2和C6）是新结构化合物。奥米克欣B1-B4显示出优良的抗甲型流感病毒活性，其IC50在1 µM左右，选择指数（SI）为100~300。奥米克欣B1~B4同时显示出对人冠状病毒HCoV-229E的显著抑制活性。综上，通过综合利用多组学技术与数据分析，从链霉菌1647发酵产物中发现了一组新型具有抗病毒活性的类四肽化合物，显示微生物次级代谢产物是新型抗病毒抗生素的宝贵资源。

关键词：多组学抗甲型流感病毒抗冠状病毒链霉菌1647 类四肽化合物

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潘胡丹：基于组学技术发现中药复方抗关节炎作用机理（2021年7月23日）

2021年10月23日

关键词：医学

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

摘要：

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。我们的数据包含了原代肝细胞体外培养去分化过程中详细的多组学分析结果，包括2196个蛋白质、2056个泛素化修饰位点和4932个磷酸化修饰位点。这项研究表明，PHC去分化过程中基因转录水平和蛋白质表达量之间的相关性较低。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。其中，有404种蛋白质同时具有泛素化修饰位点和磷酸化修饰位点，被鉴定为与去分化事件有关的关键蛋白。最终，Ptbp1、Hnrpd、Hnrnpu和Srrm2被鉴定为PHC去分化过程中的hub分子。综上所述，我们的数据为抑制原代肝细胞体外培养去分化提供了潜在靶点分子及新的见解。

关键词：去分化原代肝细胞翻译后修饰泛素化蛋白质组学磷酸化蛋白质组学转录组学

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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

摘要：

由于过敏性疾病在世界范围内流行且尚无治愈方法，因此有必要探讨其病理生理机制。由于过敏性疾病与肠道菌群失调相关，本研究从宿主与微生物的分子层面，结合代谢组学和微生物组学，寻找可能的机制。本研究对SD大鼠注射青蒿花粉提取物以诱导其对花粉的过敏反应，这种过敏反应降低了血液中的缬氨酸、异亮氨酸、天门冬氨酸、谷氨酸、谷氨酰胺、吲哚丙酸和肌醇浓度，并减少了粪便中的短链脂肪酸（SCFA）。来自于瘤胃球菌科（Ruminococcaceae）、毛螺菌科（Lachnospiraceae）和梭状芽孢杆菌（Clostridiales）的几个有益菌属在模型组中表达减少，而幽门螺杆菌Helicobacter 和阿克曼氏菌Akkermansia 仅在模型组中表达。此外，模型组肠道claudin-3 和肝脏脂肪酸结合蛋白表达下调，与代谢变化和细菌有关。本文的研究结果表明，氨基酸及其衍生物（尤其是缬氨酸和色氨酸的还原产物吲哚丙酸）、短链脂肪酸和肠道微生物（特别是幽门螺杆菌Helicobacter 和阿克曼氏菌Akkermansia）的改变可能通过抑制claudin蛋白表达和影响黏液层而破坏肠道屏障功能，进而导致花粉过敏。

关键词：代谢组学肠道菌群花粉过敏过敏性疾病肠道屏障功能紊乱

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标题作者时间类型操作

Sepsis biomarkers: an omics perspective

null

期刊论文

Deciphering the pharmacological mechanism of Guan-Jie-Kang in treating rat adjuvant-induced arthritis using omics

Hudan Pan, Yanfang Zheng, Zhongqiu Liu, Zhongwen Yuan, Rutong Ren, Hua Zhou, Ying Xie, Liang Liu

期刊论文

Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

期刊论文

Systems understanding of plant–pathogen interactions through genome-wide protein–protein interaction networks

Hong LI,Ziding ZHANG

期刊论文

扩大多元回归方法在跨组学研究中的范围

Xiaoxi Hu, Yue Ma, Yakun Xu, Peiyao Zhao, Jun Wang

期刊论文

促进肝癌致癌活性和细胞代谢的新型介质——miR-516a-3p

芮韬, 张学优, 冯时, 黄海涛, 詹少伟, 谢海洋, 周琳, 郑树森, 凌琪

期刊论文

Long-term cultivation and meta-omics reveal methylotrophic methanogenesis in hydrocarbon-impacted habitats

Yi-Fan Liu,Jing Chen,Zhong-Lin Liu,Zhao-Wei Hou,Bo Liang,Li-Ying Wang,Lei Zhou,Li-Bin Shou,Dan-Dan Lin,Shi-Zhong Yang,Jin-Feng Liu,Xiao-Lin Wu,Ji-Dong Gu,Bo-Zhong Mu,

期刊论文

多组学导向的链霉菌1647产生的奥米克欣的发现——一组抗甲型流感病毒和冠状病毒HCoV-229E的活性类四肽化合物

孙红敏, 李星星, 陈明华, 钟鸣, 李怡华, 王琨, 杜郁, 甄心, 高荣梅, 巫晔翔, 侍媛媛, 余利岩, 车永胜, 李玉环, 蒋建东, 洪斌, 司书毅

期刊论文

潘胡丹：基于组学技术发现中药复方抗关节炎作用机理（2021年7月23日）

2021年10月23日

会议视频

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

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

期刊论文

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