Technology Research and Development Project 2: Antibiotics sequencing and drug discovery

项目概要 质谱法基于将生物分子破碎成更小的碎片，并利用碎片 质量作为识别和量化生物分子的指纹。它是主导技术 研究健康和患病组织中的活性分子，并识别蛋白质靶标和天然产物 用于新疗法。当最初的提案计算质谱中心（CCMS）成立时 2007 年提交的报告指出，缺乏足够的计算工具来分析质谱数据 关键瓶颈。在新实验技术的应用方面取得了巨大成功，例如 FTMS、ETD、HCD、自上而下的质谱分析等，CCMS 的任务仍然是 下一代计算技术的开发并将其应用于开放实验。在 根据这项提议，我们将利用我们在计算蛋白质组学不同子领域的最新成果，并将 进一步分支到以前未探索的 MS 应用。我们将特别关注桥接蛋白质组学 和基因组技术利用6个技术研发平台。 具体来说，我们将（a）应用蛋白质组学方法来发现异常的癌症基因和 分析抗体库； (b) 对天然抗生素进行测序； (c) 通过光谱整理光谱数据 档案和网络； (d) 开发肽鉴定的通用工具； (e) 开发自上而下的工具 蛋白质组学； (f) 分析多重光谱。该技术平台由大量协作生物医学研究驱动，其中使用 CCMS 开发的工具对于其成功至关重要。这些 研究包括 (a) 解开人类疾病中的组合组蛋白密码； (b) 蛋白质组学 口腔微生物组和多菌感染的研究方法； (c) 检测物种间的化学相互作用； (d) 开发乙酰组治疗调节的系统方法； （五） 开发单克隆和多克隆抗体测序工具； (f) 开发乳腺癌疫苗； (g) 临床癌症蛋白质组学； (h) 发现羊毛硫抗生素； (i) 发现蛋白质组生物标志物 癌症患者的药物毒性； (j) 识别白内障晶状体中的蛋白质-蛋白质相互作用和翻译后修饰。这些项目需要在广泛的主题上进行三方协作 涉及来自不同机构的生物医学科学家、质谱学家和计算科学家。 CCMS 还将培训来自世界各地的学生和实践科学家进行计算蛋白质组学、 并对蛋白质组学界进行有关现代计算质谱学的教育，以鼓励其 广泛采用。

Project Summary Mass spectrometry is based on fragmenting biological molecules into smaller pieces, and using the fragment masses as a fingerprint for identifying and quantifying bio-molecules. It is the dominant technology for studying active molecules in healthy and diseased tissue, and identifying protein targets and natural products for novel therapeutics. When the initial proposal Center for Computational Mass Spectrometry (CCMS) was submitted in 2007, the lack of adequate computational tools for analyzing mass spectrometry data was the the key bottleneck. With great success in enabling applications of new experimental techniques such as FTMS, ETD, HCD, top-down mass spectrometry, and many others, the mandate of CCMS continues to be the development of next generation computational technologies and to apply them to open experimental. In this proposal, we will capitalize on our recent results in diverse subfields of computational proteomics and will further branch into previously unexplored MS applications. We will focus specifically on bridging proteomics and genomics technologies using 6 technology research and development platforms. Specifically, we will (a) apply proteogenomics approach for the discovery of abberant cancer genes and analyzing antibody repertoires; (b) sequence natural antibiotics; (c) collate spectral data through spectral archives and networks; (d) develop universal tools for peptide identification; (e) develop tools for top-down proteomics; and, (f) analyzing multiplexed spectra. The technology platforms are driven by a multitude of collaborative biomedical studies where the use of CCMS developed tools is essential for their success. These studies include (a) unraveling the combinatorial histone code in human diseases; (b) a proteogenomics approach to studies of oral microbiome and polybacterial infections; (c) detecting inter-species chemical interactions; (d) developing a systems approach towards the therapeutic modulation of the acetylome ; (e) developing tools for monoclonal and polyclonal antibody sequencing; (f) development of breast cancer vaccines; (g) clinical cancer proteogenomics; (h) discovery of lantibiotics; (i) discovering proteomic biomarkers for drug toxicity in cancer patients; and, (j) identifying protein-protein interactions and post-translational modifications in cataractous lens. These projects require three-way collaborative efforts on a wide range of topics involving biomedical scientists, mass spectrometrists, and computational scientists from various institutions. CCMS will also train students and practicing scientists from all over the world in computational proteomics, and educate the proteomics community about modern computational mass spectrometry to encourage its wide adoption.