Akbani Rehan, Becker Karl-Friedrich, Carragher Neil, Goldstein Ted, de Koning Leanne, Korf Ulrike, Liotta Lance, Mills Gordon B, Nishizuka Satoshi S, Pawlak Michael, Petricoin Emanuel F, Pollard Harvey B, Serrels Bryan, Zhu Jingchun
From the *University of Texas M.D. Anderson Cancer Center, Houston, Texas;
‡Technische Universität München, München, Germany;
Mol Cell Proteomics. 2014 Jul;13(7):1625-43. doi: 10.1074/mcp.O113.034918. Epub 2014 Apr 28.
Reverse phase protein array (RPPA) technology introduced a miniaturized "antigen-down" or "dot-blot" immunoassay suitable for quantifying the relative, semi-quantitative or quantitative (if a well-accepted reference standard exists) abundance of total protein levels and post-translational modifications across a variety of biological samples including cultured cells, tissues, and body fluids. The recent evolution of RPPA combined with more sophisticated sample handling, optical detection, quality control, and better quality affinity reagents provides exquisite sensitivity and high sample throughput at a reasonable cost per sample. This facilitates large-scale multiplex analysis of multiple post-translational markers across samples from in vitro, preclinical, or clinical samples. The technical power of RPPA is stimulating the application and widespread adoption of RPPA methods within academic, clinical, and industrial research laboratories. Advances in RPPA technology now offer scientists the opportunity to quantify protein analytes with high precision, sensitivity, throughput, and robustness. As a result, adopters of RPPA technology have recognized critical success factors for useful and maximum exploitation of RPPA technologies, including the following: preservation and optimization of pre-analytical sample quality, application of validated high-affinity and specific antibody (or other protein affinity) detection reagents, dedicated informatics solutions to ensure accurate and robust quantification of protein analytes, and quality-assured procedures and data analysis workflows compatible with application within regulated clinical environments. In 2011, 2012, and 2013, the first three Global RPPA workshops were held in the United States, Europe, and Japan, respectively. These workshops provided an opportunity for RPPA laboratories, vendors, and users to share and discuss results, the latest technology platforms, best practices, and future challenges and opportunities. The outcomes of the workshops included a number of key opportunities to advance the RPPA field and provide added benefit to existing and future participants in the RPPA research community. The purpose of this report is to share and disseminate, as a community, current knowledge and future directions of the RPPA technology.
反相蛋白质阵列(RPPA)技术引入了一种小型化的“抗原向下”或“斑点印迹”免疫测定法,适用于定量各种生物样品(包括培养细胞、组织和体液)中总蛋白水平和翻译后修饰的相对、半定量或定量(如果存在公认的参考标准)丰度。RPPA的最新发展与更复杂的样品处理、光学检测、质量控制以及质量更好的亲和试剂相结合,以合理的每份样品成本提供了出色的灵敏度和高样品通量。这有助于对来自体外、临床前或临床样品的多个样品中的多种翻译后标记物进行大规模多重分析。RPPA的技术力量正在推动RPPA方法在学术、临床和工业研究实验室中的应用和广泛采用。RPPA技术的进步现在为科学家提供了高精度、高灵敏度、高通量和稳健性地定量蛋白质分析物的机会。因此,RPPA技术的采用者已经认识到有效且最大程度利用RPPA技术的关键成功因素,包括以下几点:分析前样品质量的保存和优化、经过验证的高亲和力和特异性抗体(或其他蛋白质亲和力)检测试剂的应用、确保蛋白质分析物准确且稳健定量的专用信息学解决方案,以及与受监管临床环境中的应用兼容的质量保证程序和数据分析工作流程。2011年、2012年和2013年,前三届全球RPPA研讨会分别在美国、欧洲和日本举行。这些研讨会为RPPA实验室人员、供应商和用户提供了分享和讨论结果、最新技术平台、最佳实践以及未来挑战与机遇的机会。研讨会的成果包括推进RPPA领域并为RPPA研究社区的现有和未来参与者提供更多益处的一些关键机遇。本报告的目的是作为一个群体分享和传播RPPA技术的当前知识和未来方向。