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Prediction of Lung Adenocarcinoma Driver Genes Through Protein–Protein Interaction Networks Utilizing GenePlexus 利用GenePlexus通过蛋白-蛋白相互作用网络预测肺腺癌驱动基因。
IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-18 DOI: 10.1002/pmic.202400296
Fei Yuan, Yu-Hang Zhang, FeiMing Huang, Xiaoyu Cao, Lei Chen, JiaBo Li, WenFeng Shen, KaiYan Feng, YuSheng Bao, Tao Huang, Yu-Dong Cai

Lung adenocarcinoma, a subtype of lung cancer, is produced by uncontrolled proliferation of somatic cells affected by some tumorigenic factors. The origin of this disease can be attributed to the concept of “cancer driver,” which links the occurrence of tumor with specific changes in some key genes. These key genes can be identified at various molecular levels. Our innovative method uses a groundbreaking computing technology called GenePlexus to mine new genes related to lung adenocarcinoma. Initially, a vast network was synthesized from protein-protein interactions. Utilizing GenePlexus, we traversed paths interlinking aberrant genes across different layers and pinpointed emerging candidate genes situated on these trajectories. Finally, the candidate genes that were obtained underwent a series of filtering processes, including a permutation test, interaction test, and enrichment test. Compared with the shortest path method, GenePlexus has identified previously neglected genes involved in lung adenocarcinoma. For example, genes such as EGR2, EPHA3, FGFR4, HOXB1, and HEY1 play key roles at multiple molecular levels, including methylation, microRNA, mRNA and mutation, which affect tumorigenesis and lung cancer progression. These genes regulate various processes, from gene expression and cell proliferation to drug resistance to therapeutic drugs and the progress of lung adenocarcinoma.

肺腺癌是肺癌的一种亚型,是由一些致瘤因素影响的体细胞不受控制的增殖而产生的。这种疾病的起源可以归因于“癌症驱动者”的概念,它将肿瘤的发生与一些关键基因的特定变化联系起来。这些关键基因可以在不同的分子水平上进行鉴定。我们的创新方法使用了一种名为GenePlexus的突破性计算技术来挖掘与肺腺癌相关的新基因。最初,一个巨大的网络是由蛋白质之间的相互作用合成的。利用GenePlexus,我们遍历了不同层次的异常基因相互连接的路径,并确定了位于这些轨迹上的新兴候选基因。最后,对获得的候选基因进行一系列筛选,包括置换测试、相互作用测试和富集测试。与最短路径方法相比,GenePlexus已经确定了以前被忽视的与肺腺癌相关的基因。例如,EGR2、EPHA3、FGFR4、HOXB1和HEY1等基因在多个分子水平上发挥关键作用,包括甲基化、microRNA、mRNA和突变,影响肿瘤的发生和肺癌的进展。这些基因调节各种过程,从基因表达和细胞增殖到对治疗药物的耐药性和肺腺癌的进展。
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引用次数: 0
Advancements in Global Phosphoproteomics Profiling: Overcoming Challenges in Sensitivity and Quantification 全球磷蛋白组学分析的进展:克服敏感性和定量方面的挑战。
IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-18 DOI: 10.1002/pmic.202400087
Gul Muneer, Ciao-Syuan Chen, Yu-Ju Chen

Protein phosphorylation introduces post-genomic diversity to proteins, which plays a crucial role in various cellular activities. Elucidation of system-wide signaling cascades requires high-performance tools for precise identification and quantification of dynamics of site-specific phosphorylation events. Recent advances in phosphoproteomic technologies have enabled the comprehensive mapping of the dynamic phosphoproteomic landscape, which has opened new avenues for exploring cell type-specific functional networks underlying cellular functions and clinical phenotypes. Here, we provide an overview of the basics and challenges of phosphoproteomics, as well as the technological evolution and current state-of-the-art global and quantitative phosphoproteomics methodologies. With a specific focus on highly sensitive platforms, we summarize recent trends and innovations in miniaturized sample preparation strategies for micro-to-nanoscale and single-cell profiling, data-independent acquisition mass spectrometry (DIA-MS) for enhanced coverage, and quantitative phosphoproteomic pipelines for deep mapping of cell and disease biology. Each aspect of phosphoproteomic analysis presents unique challenges and opportunities for improvement and innovation. We specifically highlight evolving phosphoproteomic technologies that enable deep profiling from low-input samples. Finally, we discuss the persistent challenges in phosphoproteomic technologies, including the feasibility of nanoscale and single-cell phosphoproteomics, as well as future outlooks for biomedical applications.

蛋白质磷酸化引入了蛋白质的后基因组多样性,在各种细胞活动中起着至关重要的作用。阐明系统范围内的信号级联需要高性能的工具来精确识别和量化位点特异性磷酸化事件的动态。磷蛋白质组学技术的最新进展使动态磷蛋白质组学景观的全面绘制成为可能,这为探索细胞功能和临床表型背后的细胞类型特异性功能网络开辟了新的途径。在这里,我们概述了磷蛋白质组学的基础和挑战,以及技术的发展和当前最先进的全球和定量磷蛋白质组学方法。在高度敏感的平台上,我们总结了用于微到纳米尺度和单细胞分析的小型化样品制备策略的最新趋势和创新,用于增强覆盖范围的数据独立获取质谱(DIA-MS),以及用于深度绘制细胞和疾病生物学的定量磷蛋白质组学管道。磷蛋白质组学分析的每个方面都提出了独特的挑战和改进和创新的机会。我们特别强调了不断发展的磷蛋白质组学技术,这些技术可以从低输入样本中进行深度分析。最后,我们讨论了磷蛋白质组学技术的持续挑战,包括纳米级和单细胞磷蛋白质组学的可行性,以及生物医学应用的未来前景。
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引用次数: 0
Key Regulators of Parasite Biology Viewed Through a Post-Translational Modification Repertoire. 通过翻译后修饰库观察寄生虫生物学的关键调控因子。
IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-17 DOI: 10.1002/pmic.202400120
Naiwen Zhang, Ning Jiang, Qijun Chen

Parasites are the leading causes of morbidity and mortality in both humans and animals, imposing substantial socioeconomic burdens worldwide. Controlling parasitic diseases has become one of the key issues in achieving "One Health". Most parasites have sophisticated life cycles exhibiting progressive developmental stages, morphologies, and host-switching, which are controlled by various regulatory machineries including protein post-translational modifications (PTMs). PTMs have emerged as a key mechanism by which parasites modulate their virulence, developmental transitions, and environmental adaptations. PTMs are enzyme-mediated additions or removals of chemical groups that dynamically regulate the stability and functions of proteins and confer novel properties, playing vital roles in a variety of biological processes and cellular functions. In this review, we circumscribe how parasites utilize various PTMs to regulate their intricate lives, with a focus on the biological role of PTMs in parasite biology and pathogenesis.

寄生虫是人类和动物发病和死亡的主要原因,在世界范围内造成巨大的社会经济负担。控制寄生虫病已成为实现“同一个健康”的关键问题之一。大多数寄生虫具有复杂的生命周期,表现出渐进的发育阶段、形态和宿主转换,这些都受到包括蛋白质翻译后修饰(PTMs)在内的各种调节机制的控制。ptm已成为寄生虫调节其毒力、发育转变和环境适应的关键机制。ptm是酶介导的化学基团的添加或移除,动态调节蛋白质的稳定性和功能,并赋予新的特性,在各种生物过程和细胞功能中发挥重要作用。本文综述了寄生虫如何利用各种PTMs调控其复杂的生命,重点介绍了PTMs在寄生虫生物学和发病机制中的生物学作用。
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引用次数: 0
Standard abbreviations 标准的缩写。
IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-16 DOI: 10.1002/pmic.202470184
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引用次数: 0
Editorial Board: Proteomics 23–24'24 编委会:蛋白质组学 23-24'24
IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-16 DOI: 10.1002/pmic.202470182
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引用次数: 0
Contents: Proteomics 23–24'24 内容:蛋白质组学 23-24'24
IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-16 DOI: 10.1002/pmic.202470183
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引用次数: 0
Addressing Sample Mix-Ups: Tools and Approaches for Large-Scale Multi-Omics Studies 解决样本混淆:大规模多组学研究的工具和方法。
IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-10 DOI: 10.1002/pmic.202400271
Yingxue Fu, Zuo-Fei Yuan, Long Wu, Junmin Peng, Xusheng Wang, Anthony A. High

Advances in high-throughput omics technologies have enabled system-wide characterization of biological samples across multiple molecular levels, such as the genome, transcriptome, and proteome. However, as sample sizes rapidly increase in large-scale multi-omics studies, sample mix-ups have become a prevalent issue, compromising data integrity and leading to erroneous conclusions. The interconnected nature of multi-omics data presents an opportunity to identify and correct these errors. This review examines the potential sources of sample mix-ups and evaluates the methodologies and tools developed for detecting and correcting these errors, with an emphasis on approaches applicable to proteomics data. We categorize existing tools into three main groups: expression/protein quantitative trait loci-based, genotype concordance-based, and gene/protein expression correlation-based approaches. Notably, only a handful of tools currently utilize the proteogenomics approach for correcting sample mix-ups at the proteomics level. Integrating the strengths of current tools across diverse data types could enable the development of more versatile and comprehensive solutions. In conclusion, verifying sample identity is a critical first step to reduce bias and increase precision in subsequent analyses for large-scale multi-omics studies. By leveraging these tools for identifying and correcting sample mix-ups, researchers can significantly improve the reliability and reproducibility of biomedical research.

高通量组学技术的进步使生物样品在多个分子水平上的全系统表征成为可能,如基因组、转录组和蛋白质组。然而,随着大规模多组学研究中样本量的迅速增加,样本混淆已经成为一个普遍存在的问题,损害了数据的完整性并导致错误的结论。多组学数据的互联性为识别和纠正这些错误提供了机会。这篇综述检查了样品混淆的潜在来源,并评估了用于检测和纠正这些错误的方法和工具,重点是适用于蛋白质组学数据的方法。我们将现有的工具分为三大类:基于表达/蛋白质数量性状位点的方法、基于基因型一致性的方法和基于基因/蛋白质表达相关性的方法。值得注意的是,目前只有少数工具利用蛋白质基因组学方法在蛋白质组学水平上纠正样品混淆。跨不同数据类型集成当前工具的优势可以开发更通用和全面的解决方案。总之,验证样本身份是减少偏差和提高后续大规模多组学研究分析精度的关键第一步。通过利用这些工具来识别和纠正样本混淆,研究人员可以显著提高生物医学研究的可靠性和可重复性。
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引用次数: 0
An In-Depth Coho Salmon (Oncorhynchus kisutch) Ovarian Follicle Proteome Reveals Coordinated Changes Across Diverse Cellular Processes during the Transition From Primary to Secondary Growth 一项深入的银鲑(Oncorhynchus kisutch)卵巢卵泡蛋白质组揭示了从初级生长到次级生长过渡过程中多种细胞过程的协调变化。
IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-08 DOI: 10.1002/pmic.202400311
Emma Timmins-Schiffman, Jennifer Telish, Chelsea Field, Chris Monson, José M. Guzmán, Brook L. Nunn, Graham Young, Kristy Forsgren

Teleost fishes are a highly diverse, ecologically essential group of aquatic vertebrates that include coho salmon (Oncorhynchus kisutch). Coho are semelparous and all ovarian follicles develop synchronously. Owing to their ubiquitous distribution, teleosts provide critical sources of food worldwide through subsistence, commercial fisheries, and aquaculture. Enhancement of hatchery practices requires detailed knowledge of teleost reproductive physiology. Despite decades of research on teleost reproductive processes, an in-depth proteome of teleost ovarian development has yet to be generated. We have described a coho salmon ovarian proteome of over 5700 proteins, generated with data independent acquisition, revealing the proteins that change through the transition from primary to secondary ovarian follicle development. This transition is critical during the onset of puberty and for determining egg quality and embryonic development. Primary follicle development was marked by differential abundances of proteins in carbohydrate metabolism, protein turnover, and the complement pathway, suggesting elevated metabolism as the follicles develop through stages of oogenesis. The greatest proteomic shift occurred during the transition from primary to secondary follicle growth, with increased abundance of proteins underlying cortical alveoli formation, extracellular matrix reorganization, iron binding, and cell–cell signaling. This work provides a foundation for identifying biomarkers of salmon oocyte stage and quality.

硬骨鱼是一种高度多样化的生态重要水生脊椎动物,包括银鲑(Oncorhynchus kisutch)。Coho是半产的,所有的卵巢卵泡同步发育。由于硬骨鱼无处不在,它们通过生计、商业渔业和水产养殖在世界范围内提供了重要的食物来源。加强孵化场实践需要对硬骨鱼生殖生理学有详细的了解。尽管对硬骨鱼生殖过程进行了数十年的研究,但硬骨鱼卵巢发育的深入蛋白质组尚未产生。我们描述了一个超过5700个蛋白质的银鲑卵巢蛋白质组,通过数据独立采集生成,揭示了从初级到次级卵巢卵泡发育转变的蛋白质。这种转变在青春期开始时至关重要,并决定卵子质量和胚胎发育。初级卵泡发育以碳水化合物代谢、蛋白质转换和补体途径中不同丰度的蛋白质为标志,表明随着卵泡在卵子发生阶段的发育,代谢水平升高。最大的蛋白质组学变化发生在从初级到次级卵泡生长的转变过程中,随着皮层肺泡形成、细胞外基质重组、铁结合和细胞-细胞信号传导的蛋白质丰度增加。本工作为鉴定鲑鱼卵母细胞分期和质量的生物标志物奠定了基础。
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引用次数: 0
Reduction of Chemokine CXCL9 Expression by Omega-3 Fatty Acids via ADP-Ribosylhydrolase ARH3 in MIN6 Insulin-Producing Cells Omega-3脂肪酸通过adp -核糖基水解酶ARH3降低MIN6胰岛素生成细胞趋化因子CXCL9的表达
IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-08 DOI: 10.1002/pmic.202400053
Youngki You, Soumyadeep Sarkar, Cailin Deiter, Emily C. Elliott, Carrie D. Nicora, Raghavendra G. Mirmira, Lori Sussel, Ernesto S. Nakayasu

Type 1 diabetes (T1D) results from the autoimmune destruction of the insulin-producing β cells of the pancreas. Omega-3 fatty acids protect β cells and reduce the incidence of T1D, but the mechanism is poorly understood. We have shown that omega-3 fatty acids reduce pro-inflammatory cytokine-mediated β-cell apoptosis by upregulating the expression of the ADP-ribosylhydrolase ARH3. Here, we further investigate the β-cell protection mechanism of ARH3 by performing siRNA analysis of its gene Adprhl2 in MIN6 insulin-producing cells, subsequent treatment with a cocktail of the pro-inflammatory cytokines IL-1β + IFN-γ + TNF-α, followed by proteomics analysis. ARH3 regulated proteins from several pathways related to the nucleus (splicing, RNA surveillance, and nucleocytoplasmic transport), mitochondria (metabolic pathways), and endoplasmic reticulum (protein folding). ARH3 also regulated the levels of proteins related to antigen processing and presentation, and the chemokine-signaling pathway. We further studied the role of ARH3 in regulating the chemokine CXCL9. We found that ARH3 reduces the cytokine-induced expression of CXCL9, which is dependent on omega-3 fatty acids. In conclusion, we demonstrate that omega-3 fatty acids regulate CXCL9 expression via ARH3, which may have a role in protecting β cells from immune attack thereby preventing T1D development.

Significance of the Study: Omega-3 fatty acids have a variety of health benefits. In type 1 diabetes, omega-3 fatty acids reduce the islet autoimmune response and the disease development. Here, we studied the pathways regulated by the adenosine diphosphate (ADP)-ribosylhydrolase ARH3, a protein whose expression is regulated by omega-3 fatty acids. We showed that ARH3 reduces the expression of chemokines in response to omega-3 fatty acids. This represents an anti-inflammatory mechanism of omega-3 fatty acids that might be involved with protection against type 1 diabetes development.

1型糖尿病(T1D)是由于自身免疫破坏胰腺产生胰岛素的β细胞引起的。Omega-3脂肪酸保护β细胞并降低T1D的发生率,但其机制尚不清楚。我们已经证明,omega-3脂肪酸通过上调adp核糖基水解酶ARH3的表达来减少促炎细胞因子介导的β细胞凋亡。在这里,我们进一步研究了ARH3的β细胞保护机制,通过在MIN6胰岛素产生细胞中对其基因Adprhl2进行siRNA分析,随后用促炎细胞因子IL-1β + IFN-γ + TNF-α的鸡尾酒治疗,然后进行蛋白质组学分析。ARH3调节与细胞核(剪接、RNA监视和核胞质运输)、线粒体(代谢途径)和内质网(蛋白质折叠)相关的几种途径的蛋白质。ARH3还调节与抗原加工和呈递相关的蛋白水平,以及趋化因子信号通路。我们进一步研究了ARH3在调节趋化因子CXCL9中的作用。我们发现ARH3降低细胞因子诱导的CXCL9的表达,而CXCL9依赖于omega-3脂肪酸。综上所述,我们证明了omega-3脂肪酸通过ARH3调节CXCL9的表达,这可能在保护β细胞免受免疫攻击从而防止T1D的发展中起作用。研究意义:Omega-3脂肪酸具有多种健康益处。在1型糖尿病中,omega-3脂肪酸降低胰岛自身免疫反应和疾病发展。在这里,我们研究了由二磷酸腺苷(ADP)-核糖基水解酶ARH3调节的途径,这是一种由omega-3脂肪酸调节表达的蛋白质。我们发现ARH3降低了对omega-3脂肪酸的趋化因子的表达。这表明omega-3脂肪酸的抗炎机制可能与预防1型糖尿病的发生有关。
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引用次数: 0
Prediction of Plant Resistance Proteins Using Alignment-Based and Alignment-Free Approaches 利用基于配位和无配位方法预测植物抗性蛋白
IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-24 DOI: 10.1002/pmic.202400261
Pushpendra Singh Gahlot, Shubham Choudhury, Nisha Bajiya, Nishant Kumar, Gajendra P. S. Raghava

Plant disease resistance (PDR) proteins are critical in identifying plant pathogens. Predicting PDR protein is essential for understanding plant–pathogen interactions and developing strategies for crop protection. This study proposes a hybrid model for predicting and designing PDR proteins against plant-invading pathogens. Initially, we tried alignment-based approaches, such as Basic Local Alignment Search Tool (BLAST) for similarity search and MERCI for motif search. These alignment-based approaches exhibit very poor coverage or sensitivity. To overcome these limitations, we developed alignment-free or machine learning (ML)-based methods using compositional features of proteins. Our ML-based model, developed using compositional features of proteins, achieved a maximum performance area under the receiver operating characteristic curve (AUROC) of 0.91. The performance of our model improved significantly from AUROC of 0.91–0.95 when we used evolutionary information instead of protein sequence. Finally, we developed a hybrid or ensemble model that combined our best ML model with BLAST and obtained the highest AUROC of 0.98 on the validation dataset. We trained and tested our models on a training dataset and evaluated them on a validation dataset. None of the proteins in our validation dataset are more than 40% similar to proteins in the training dataset. One of the objectives of this study is to facilitate the scientific community working in plant biology. Thus, we developed an online platform for predicting and designing plant resistance proteins, “PlantDRPpred” (https://webs.iiitd.edu.in/raghava/plantdrppred).

植物抗病性(PDR)蛋白是识别植物病原体的关键。预测植物抗病蛋白对于了解植物与病原体之间的相互作用和制定作物保护策略至关重要。本研究提出了一种预测和设计抗植物病原菌 PDR 蛋白的混合模型。起初,我们尝试了基于比对的方法,如用于相似性搜索的基本局部比对搜索工具(BLAST)和用于主题搜索的 MERCI。这些基于比对的方法显示出很低的覆盖率或灵敏度。为了克服这些局限性,我们利用蛋白质的组成特征开发了无配对或基于机器学习(ML)的方法。我们利用蛋白质的组成特征开发的基于 ML 的模型的接收者操作特征曲线下面积(AUROC)达到了 0.91 的最高性能。当我们使用进化信息而不是蛋白质序列时,我们模型的性能在 0.91-0.95 的 AUROC 基础上有了显著提高。最后,我们开发了一个混合模型或集合模型,将最佳 ML 模型与 BLAST 结合在一起,在验证数据集上获得了最高的 AUROC(0.98)。我们在训练数据集上对模型进行了训练和测试,并在验证数据集上对模型进行了评估。在我们的验证数据集中,没有一个蛋白质与训练数据集中的蛋白质相似度超过 40%。本研究的目标之一是为从事植物生物学研究的科学界提供便利。因此,我们开发了一个用于预测和设计植物抗性蛋白的在线平台 "PlantDRPpred" (https://webs.iiitd.edu.in/raghava/plantdrppred)。
{"title":"Prediction of Plant Resistance Proteins Using Alignment-Based and Alignment-Free Approaches","authors":"Pushpendra Singh Gahlot,&nbsp;Shubham Choudhury,&nbsp;Nisha Bajiya,&nbsp;Nishant Kumar,&nbsp;Gajendra P. S. Raghava","doi":"10.1002/pmic.202400261","DOIUrl":"10.1002/pmic.202400261","url":null,"abstract":"<div>\u0000 \u0000 <p>Plant disease resistance (PDR) proteins are critical in identifying plant pathogens. Predicting PDR protein is essential for understanding plant–pathogen interactions and developing strategies for crop protection. This study proposes a hybrid model for predicting and designing PDR proteins against plant-invading pathogens. Initially, we tried alignment-based approaches, such as Basic Local Alignment Search Tool (BLAST) for similarity search and MERCI for motif search. These alignment-based approaches exhibit very poor coverage or sensitivity. To overcome these limitations, we developed alignment-free or machine learning (ML)-based methods using compositional features of proteins. Our ML-based model, developed using compositional features of proteins, achieved a maximum performance area under the receiver operating characteristic curve (AUROC) of 0.91. The performance of our model improved significantly from AUROC of 0.91–0.95 when we used evolutionary information instead of protein sequence. Finally, we developed a hybrid or ensemble model that combined our best ML model with BLAST and obtained the highest AUROC of 0.98 on the validation dataset. We trained and tested our models on a training dataset and evaluated them on a validation dataset. None of the proteins in our validation dataset are more than 40% similar to proteins in the training dataset. One of the objectives of this study is to facilitate the scientific community working in plant biology. Thus, we developed an online platform for predicting and designing plant resistance proteins, “PlantDRPpred” (https://webs.iiitd.edu.in/raghava/plantdrppred).</p>\u0000 </div>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 5-6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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