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Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma

《医学前沿(英文)》 2024年 第18卷 第2期   页码 375-393 doi: 10.1007/s11684-023-1020-z

摘要: Retroperitoneal liposarcoma (RLPS) is the main subtype of retroperitoneal soft sarcoma (RSTS) and has a poor prognosis and few treatment options, except for surgery. The proteomic and metabolic profiles of RLPS have remained unclear. The aim of our study was to reveal the metabolic profile of RLPS. Here, we performed proteomic analysis (n = 10), metabolomic analysis (n = 51), and lipidomic analysis (n = 50) of retroperitoneal dedifferentiated liposarcoma (RDDLPS) and retroperitoneal well-differentiated liposarcoma (RWDLPS) tissue and paired adjacent adipose tissue obtained during surgery. Data analysis mainly revealed that glycolysis, purine metabolism, pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue, whereas the tricarboxylic acid (TCA) cycle, lipid absorption and synthesis, fatty acid degradation and biosynthesis, as well as glycine, serine, and threonine metabolism were downregulated. Of particular importance, the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway (PPP) inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib. Our study not only describes the metabolic profiles of RDDLPS and RWDLPS, but also offers potential therapeutic targets and strategies for RLPS.

关键词: RLPS     proteomics     metabolomics     lipidomics     metabolism    

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    

Discovery of emerging organic pollutants in the atmosphere through an omics approach

《环境科学与工程前沿(英文)》 2023年 第17卷 第4期 doi: 10.1007/s11783-023-1645-9

摘要:

● We review the framework of discovering emerging pollutants through an omics approach.

关键词: Air pollution     Emerging pollutants     Full-component     High-resolution mass spectrometry     Omics approach    

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    

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

《医学前沿(英文)》 2022年 第16卷 第4期   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    

通过组学将中医体质理论应用于不孕症

王琦

《工程(英文)》 2023年 第30卷 第11期   页码 30-31 doi: 10.1016/j.eng.2023.05.005

mechanisms of acupuncture in the treatment of migraine based on functional magnetic resonance imaging and omics

《医学前沿(英文)》 2023年 第17卷 第5期   页码 993-1005 doi: 10.1007/s11684-023-0989-7

摘要: Migraine is one of the most prevalent and disabling neurological disease, but the current pharmacotherapies show limited efficacy and often accompanied by adverse effects. Acupuncture is a promising complementary therapy, but further clinical evidence is needed. The influence of acupuncture on migraine is not an immediate effect, and its mechanism remains unclear. This study aims to provide further clinical evidence for the anti-migraine effects of acupuncture and explore the mechanism involved. A randomized controlled trial was performed among 10 normal controls and 38 migraineurs. The migraineurs were divided into blank control, sham acupuncture, and acupuncture groups. Patients were subjected to two courses of treatment, and each treatment lasted for 5 days, with an interval of 1 day between the two courses. The effectiveness of treatment was evaluated using pain questionnaire. The functional magnetic resonance imaging (fMRI) data were analyzed for investigating brain changes induced by treatments. Blood plasma was collected for metabolomics and proteomics studies. Correlation and mediation analyses were performed to investigate the interaction between clinical, fMRI and omics changes. Results showed that acupuncture effectively relieved migraine symptoms in a way different from sham acupuncture in terms of curative effect, affected brain regions, and signaling pathways. The anti-migraine mechanism involves a complex network related to the regulation of the response to hypoxic stress, reversal of brain energy imbalance, and regulation of inflammation. The brain regions of migraineurs affected by acupuncture include the lingual gyrus, default mode network, and cerebellum. The effect of acupuncture on patients’ metabolites/proteins may precede that of the brain.

关键词: acupuncture     migraine     fMRI     metabolome     proteome    

Higher NO production in sequencing batch reactors compared to continuous stirred tank reactors: effect of feast-famine cycles

《环境科学与工程前沿(英文)》 2023年 第17卷 第4期 doi: 10.1007/s11783-023-1650-z

摘要:

● N2O emissions from a denitrifying SBR were 23 times higher than that of the CSTR.

关键词: Denitrifying N2O mitigation     SBR     CSTR     Meta-omics     PHB    

作物表型组大数据技术及装备发展研究

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

摘要:

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。本文分析了作物表型组大数据技术及装备的应用需求、产业发展形势,从物理、传输、数据、知识、应用5 个层面详细梳理了相应研发现状;从作物表型组大数据高通量获取、作物表型组大数据智能解析技术两方面着手,剖析了我国相关技术、装备、产业应用方面的问题和态势。研究建议,从底层芯片层面突破作物表型传感器关键技术,在可控开源的基础上形成自主化的表型解析技术体系,加强作物表型组大数据技术及装备标准体系建设,提出基因 – 表型 – 环境多维大数据驱动的数字育种和智慧栽培创新模式,建设作物表型组大数据技术及装备人才队伍和协作网络。

关键词: 作物表型组学;表型大数据;表型技术及装备;多组学    

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    

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    

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(HCC)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    

人工智能加速GPCR配体的发现 Review

陈伟, 宋驰, 冷梁, 张三印, 陈士林

《工程(英文)》 2024年 第32卷 第1期   页码 18-28 doi: 10.1016/j.eng.2023.09.011

摘要:

G蛋白偶联受体(GPCR)在多种生理过程中发挥着关键作用,是新药发现的重要靶标。然而,传统的GPCR配体发现方法需要投入大量的时间和资源。人工智能方法的出现为GPCR配体的识别和优化提供了有利的工具,改变了GPCR配体发现的研究方式。本文从数据资源、数据描述、模型设计等方面介绍了如何利用人工智能方法构建GPCR配体发现模型,并分析了人工智能方法在GPCR药物领域的应用;提出了一种基于人工智能方法整合多组学数据的GPCR配体筛选策略;探讨了人工智能方法在GPCR研究领域面临的挑战和未来发展方向。人工智能方法与多学科的交叉融合将提高GPCR配体发现的效率。

关键词: G蛋白偶联受体     配体     人工智能     多组学     药物发现    

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(Streptomyces sp.)1647 是20 世纪70 年代从中国南方土壤中分离的一株链霉菌,其发酵液显示优良的抗甲型流感病毒(IAV)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。本研究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。利用抗生素及次级代谢产物分析软件(antiSMASH)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(BGC)。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,确定了基因簇36 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,取名奥米克欣(omicsynin)A1~A6、奥米克欣B1~B6 和奥米克欣C1~C6,其中11 个(奥米克欣A1、奥米克欣A2、奥米克欣A6、奥米克欣B1~B3、奥米克欣B5、奥米克欣B6、奥米克欣C1、奥米克欣C2 和奥米克欣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50%抑制浓度(IC50)在1 μmol·L−1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的具有抗病毒活性的类四肽化合物,说明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    

Altered Iron-Mediated Metabolic Homeostasis Governs the Efficacy and Toxicity of Tripterygium Glycosides Tablets Against Rheumatoid Arthritis

Zihe Ding,Xiaoyue Wang,Yi Zhang,Jian Liu,Lei Wan,Tao Li,Lin Chen,Na Lin,Yanqiong Zhang,

《工程(英文)》 doi: 10.1016/j.eng.2024.04.003

摘要: Rheumatoid arthritis (RA), a globally increasing autoimmune disorder, is associated with increased disability rates due to the disruption of iron metabolism. Tripterygium glycoside tablets (TGTs), a Tripterygium wilfordii Hook. f. (TwHF)-based therapy, exhibit satisfactory clinical efficacy for RA treatment. However, drug-induced liver injury (DILI) remains a critical issue that hinders the clinical application of TGTs, and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated. To address this problem, we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis. Subsequently, we identified effective and toxic targets following experimental validation in a collagen-induced arthritis (CIA) mouse model. Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified. Intriguingly, the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids, respectively. Particularly, the signal transducer and activator of transcription 3 (STAT3)–hepcidin (HAMP)/lipocalin 2 (LCN2)–tartrate-resistant acid phosphatase type 5 (ACP5) and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4 (ACSL4)–lysophosphatidylcholine acyltransferase 3 (LPCAT3) axes were identified as key drivers of the efficacy and toxicity of TGTs. TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction, disruption of lipid metabolism, and hepatic lipid peroxidation. Notably, TGTs effectively reversed “iron–bone” disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis, subsequently leading to “iron–lipid” disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis. Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets. Collectively, our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy, offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.

关键词: Tripterygium     glycosides tablets     Rheumatoid arthritis     Iron metabolism     Clinical efficacy     Drug-induced liver injury     Clinical multi-omics data analysis    

标题 作者 时间 类型 操作

Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma

期刊论文

Sepsis biomarkers: an omics perspective

null

期刊论文

Discovery of emerging organic pollutants in the atmosphere through an omics approach

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

通过组学将中医体质理论应用于不孕症

王琦

期刊论文

mechanisms of acupuncture in the treatment of migraine based on functional magnetic resonance imaging and omics

期刊论文

Higher NO production in sequencing batch reactors compared to continuous stirred tank reactors: effect of feast-famine cycles

期刊论文

作物表型组大数据技术及装备发展研究

温维亮,郭新宇 ,张颖,顾生浩,赵春江

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

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