TR&D 5: Top-Down for the Masses

技术研发项目5：自上而下为群众服务 摘要 在质谱学中，使用完整蛋白质作为主要测量单位存在着强有力的论据。 以蛋白质组学为基础。蛋白质形式假说，它认为特定的蛋白质形式与 与表型有关，在从事翻译和基础科学的研究人员中引起强烈共鸣。在 在之前的授权期，NRTDP为发现科学制定了强有力的量化工作流程，并应用 这些工作流程流向了无数的生物系统。为了认识到我们有责任培养一个更广泛的社会，我们已经 选择创建一个完整的研发，专注于使我们的量化工作流足够强大，使它们能够 通过社区参与输出到非专家实验室。要做到这一点，这些步骤中的每一步 从样品制备和分离到质谱学检测和数据分析的工作流程将是 创新以提高健壮性。新的样品制备技术与更强大、更高的流动相结合 层析将缓解与纳米流层析相关的问题。更清洁的样品与现场配合使用 不对称离子迁移率谱(FAIMS)也将提高质谱仪的正常运行时间。除了……之外 改进了硬件的健壮性，资源还将发布更新的软件工具，包括自动驾驶 Acquire、TDPORTAL和TDVIEWER，包括简化的定量数据采集、处理和 分析工作流。这些创新的结合将使资源能够有效地出口 这些实验在内部发展成为一个社区，这个社区越来越有兴趣进行 是蛋白质形式分解的。

Technology Research and Development Project 5: Top-Down for the Masses Abstract Strong arguments exist for utilizing intact proteins as the primary unit of measurement in mass spectrometry- based proteomics. The proteoform hypothesis, which suggests that it is specific proteoforms that are most tightly linked to phenotype, resonates strongly with researchers performing both translational and basic science. In the previous granting period, the NRTDP developed potent quantitative workflows for discovery science and applied these workflows to myriad biological systems. In recognition of our duty to foster a broader community, we have chosen to create an entire TR&D focused on making our quantitative workflows robust enough that they can be exported to non-expert labs through Community Engagement. To accomplish this, each step in these workflows, from sample preparation and separation to mass spectrometric detection and data analysis will be innovated to improve robustness. New sample preparation technology coupled with more robust, higher flow chromatography will alleviate issues related to nanoflow chromatography. Cleaner samples coupled with field asymmetric ion mobility spectrometry (FAIMS) will also improve mass spectrometer up-time. In addition to improved hardware robustness, the resource will also publish updated software tools, including AUTOPILOT ACQUIRE, TDPORTAL and TDVIEWER, which include streamlined quantitative data acquisition, processing, and analysis workflows. The combination of these innovations will give the resource the capability to efficiently export the experiments developed in-house to a community that has a growing appetite for performing experiments that are proteoform-resolved.