MASH Explorer, a Comprehensive Software Environment for Top-Down Proteomics

项目摘要 在后基因组时代，蛋白质组学是下一个前沿领域，可以深入了解其功能 细胞系统在人类疾病中的应用和个性化治疗的发展。与基因组不同， 由于选择性剪接和翻译后修饰(PTM)，蛋白质组是动态的和高度复杂的。 正在兴起的自上而下的蛋白质组学是全面表征蛋白质形式的最有力的方法 由遗传变异和PTM引起的，这对于理解疾病机制和 确定新的治疗靶点。然而，用于自上而下的蛋白质组学的数据分析工具仍然处于- 发展起来的。随着最近自上而下的蛋白质组学社区的快速增长，迫切需要 开发自上而下的蛋白质组学综合分析平台。在这里，我们的目标是开发MASH探测器， 用于自上而下蛋白质组学的全面、通用和用户友好的软件环境，包括 用于数据处理和分析的离线可下载软件包(App)和在线版本 (门户网站)。具体目标是：1)开发MASH Explorer App，这是一个可下载的软件包，适用于顶层- Down蛋白质组学，可以处理来自各种供应商格式的数据，并整合多种算法 具有用户友好的图形界面的反卷积和数据库搜索；一种新的反卷积算法 高精度的数据分析和用于鉴定大蛋白的新搜索算法也将被 针对目前自上而下的Proteomcis软件工具的不足进行开发；2)开发 增强的蛋白质形式家族的自动识别和定量的新算法 鉴定低丰度蛋白质形式；3)开发MASH Explorer门户，这是一个基于Web的扩展 Mash Explorer App用于处理和共享自上而下的蛋白质组学数据。MASH资源管理器门户具有以下功能 My MASH，一个基于云的个性化在线数据处理空间，以及MASH PUBLIC，一个公共 用于长期数据存储和共享的数据库，以促进不同团体和 整个蛋白质组学社区。该项目的成功完成将创造一个强大的软件工具， Mash Explorer，用于自上而下的蛋白质组学。所有用户都可以免费使用MASH浏览器软件。 改善非专有自由软件解决方案的可获得性将显著支持 自上而下的蛋白质组学社区。因此，我们预计它将在推动这一新兴领域发挥不可或缺的作用 自上而下的蛋白质组学，并实现其在生物医学研究的全部潜力。

Project Summary In the post-genomic era, proteomics is the next frontier allowing an in-depth understanding of the function of cellular systems in human diseases and the development of personalized treatments. Unlike the genome, the proteome is dynamic and highly complex due to alternative splicing and post-translational modifications (PTMs). The emerging top-down proteomics is the most powerful method to comprehensively characterize proteoforms that arise from genetic variations and PTMs, which is critical for understanding disease mechanisms and identifying new therapeutic targets. However, data analysis tools for top-down proteomics remain under- developed. With the recent rapid growth of the top-down proteomics community, there is an urgent need to develop a comprehensive analysis platform for top-down proteomics. Herein, we aim to develop MASH Explorer, a comprehensive, universal, and user-friendly software environment for top-down proteomics, which includes both an offline downloadable software package (App) and an online version for data processing and analysis (Portal). The specific aims are: 1) to develop MASH Explorer App, a downloadable software package for top- down proteomics that can process data from various vendor formats and incorporate multiple algorithms for deconvolution and database search with user-friendly graphical interfaces; a novel deconvolution algorithm for high-accuracy data analysis and a novel search algorithm for identification of large proteins will also be developed to address the deficiency in the currently available top-down proteomcis software tools; 2) to develop novel algorithms for the automated identification and quantification of proteoform families with enhanced identification of low-abundance proteoforms; 3) to develop MASH Explorer Portal, a web-based extension of MASH Explorer App for processing and sharing top-down proteomics data. The MASH Explorer Portal features my MASH, a cloud-based personalized space for online data processing, as well as MASH public, a public database for long-term data storage and sharing to facilitate the collaboration among various groups and the entire proteomics community. The successful completion of this project will create a powerful software tool, MASH Explorer, for top-down proteomics. The MASH Explorer software will be freely available to all users. Improving the accessibility of non-proprietary free software solutions will significantly bolster the growth of the top-down proteomics community. Hence, we envision it will play integral roles in advancing the burgeoning field of top-down proteomics and realize its full potential for biomedical research.