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Autophagy modulator scoring system: a user-friendly tool for quantitative analysis of methodological integrity of chemical autophagy modulator studies.
Autophagy ( IF 14.6 ) Pub Date : 2019-12-23 , DOI: 10.1080/15548627.2019.1704119
Yu Dong 1 , Yuanjia Hu 1 , Sovan Sarkar 2 , Wei-Xing Zong 3 , Min Li 4 , Du Feng 5 , Ju-Xian Song 6, 7 , Min Li 7 , Diego L Medina 8, 9 , Jieqiong Tan 10 , Zhuohua Zhang 11 , Zhenyu Yue 12 , Jia-Hong Lu 1
Affiliation  

Over the past 20 years (1999-2019), we have witnessed a rapid increase in publications involving chemical macroautophagy/autophagy modulators. However, an overview of the methodologies used in these studies is still lacking, and methodology flaws are frequently observed in some reports. To provide an objective and quantitative analysis of studies involving autophagy modulators, we present an Autophagy Modulator Scoring System (AMSS), which is designed to evaluate methodological integrity. AMSS-A includes the autophagy characterization by 4 aspects, namely, autophagosome quantification, autophagy-related biochemical changes, autophagy substrate degradation, and autophagic flux. AMSS-B contains the pharmacological and functional characteristics of chemical autophagy modulators, including lysosomal function, drug targets, autophagy-dependent pharmacological effects, and validation in multiple cell lines and in vivo models. Our analysis shows that of the 385 studies reporting chemical autophagy modulators, only 142 single studies had examined all 4 aspects of autophagy characterization in AMSS-A, and only 10 out of 142 studies had fulfilled all the AMSS criteria in a single study. A comprehensive analysis of the methodologies used in all the studies was made, along with a summary of studies that demonstrated the highest methodological integrity based on AMSS ranking. To test the reliability of the AMSS, a co-efficiency analysis of scores and co-citation values in the co-citation network was performed, and a significant co-efficiency was obtained. Collectively, AMSS provides insight into the methodological integrity of autophagy modulators studies and also offers a user-friendly toolkit to help choose appropriate assays to characterize autophagy modulators.Abbreviations: 3-MA: 3-methyladenine; AMSS: Autophagy Modulator Scoring System; ATG: autophagy-related; BAF: bafilomycin A1; BECN1: beclin 1; CQ: chloroquine; GFP: green fluorescent protein; LC3: microtubule associated protein 1 light chain 3; mRFP: monomeric red fluorescent protein; MTOR: mechanistic target of rapamycin kinase; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate.

中文翻译:

自噬调节剂评分系统:一种用户友好的工具,用于定量分析化学自噬调节剂研究的方法完整性。

在过去的 20 年(1999-2019)中,我们目睹了涉及化学巨自噬/自噬调节剂的出版物的快速增长。然而,仍然缺乏对这些研究中使用的方法的概述,并且在一些报告中经常观察到方法缺陷。为了对涉及自噬调节剂的研究进行客观和定量分析,我们提出了一种自噬调节剂评分系统 (AMSS),旨在评估方法的完整性。AMSS-A包括4个方面的自噬表征,即自噬体定量、自噬相关生化变化、自噬底物降解和自噬通量。AMSS-B 包含化学自噬调节剂的药理和功能特性,包括溶酶体功能、药物靶点、自噬依赖性药理作用,以及在多个细胞系和体内模型中的验证。我们的分析表明,在报告化学自噬调节剂的 385 项研究中,只有 142 项研究检查了 AMSS-A 中自噬表征的所有 4 个方面,而 142 项研究中只有 10 项在一项研究中满足了所有 AMSS 标准。对所有研究中使用的方法进行了全面分析,并总结了基于 AMSS 排名证明最高方法完整性的研究。为了测试AMSS的可靠性,对共被引网络中的分数和共被引值进行了共效分析,得到了显着的共效。集体,AMSS 提供了对自噬调节剂研究方法完整性的洞察,还提供了一个用户友好的工具包,以帮助选择合适的测定来表征自噬调节剂。缩写:3-MA:3-甲基腺嘌呤;AMSS:自噬调节剂评分系统;ATG:自噬相关;BAF:巴弗洛霉素A1;BECN1:beclin 1;CQ:氯喹;GFP:绿色荧光蛋白;LC3:微管相关蛋白1轻链3;mRFP:单体红色荧光蛋白;MTOR:雷帕霉素激酶的机制靶点;PtdIns3K:磷脂酰肌醇 3-激酶;PtdIns3P:3-磷酸磷脂酰肌醇。氯喹;GFP:绿色荧光蛋白;LC3:微管相关蛋白1轻链3;mRFP:单体红色荧光蛋白;MTOR:雷帕霉素激酶的机制靶点;PtdIns3K:磷脂酰肌醇 3-激酶;PtdIns3P:3-磷酸磷脂酰肌醇。氯喹;GFP:绿色荧光蛋白;LC3:微管相关蛋白1轻链3;mRFP:单体红色荧光蛋白;MTOR:雷帕霉素激酶的机制靶点;PtdIns3K:磷脂酰肌醇 3-激酶;PtdIns3P:3-磷酸磷脂酰肌醇。
更新日期:2019-12-17
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