Center for Computational Mass Spectrometry

描述：质谱学是基于将生物分子裂解成更小的片段，并使用碎片质量作为指纹来识别和定量生物分子。它是研究健康和疾病组织中的活性分子，识别蛋白质靶标和天然产物用于新疗法的主导技术。当2007年提交最初的计算质谱学中心(CCMS)提案时，缺乏足够的计算工具来分析质谱学数据是关键的瓶颈。随着FTMS、ETD、HCD、自上而下质谱学等新实验技术的应用取得巨大成功，CCMS的任务继续是开发下一代计算技术并将其应用于开放实验。在这项提案中，我们将利用我们在计算蛋白质组学不同子领域的最新结果，并将进一步分支到以前未探索的MS应用领域。我们将特别关注利用6个技术研发平台连接蛋白质组学和基因组学技术。具体地说，我们将(A)应用蛋白质组学方法发现癌症基因和分析抗体库；(B)对天然抗生素进行测序；(C)通过光谱档案和网络整理光谱数据；(D)开发识别多肽的通用工具；(E)开发自上而下的蛋白质组学工具；以及(F)分析多重光谱。这些技术平台是由大量合作的生物医学研究推动的，在这些研究中，CCMS开发的工具的使用对于它们的成功至关重要。这些研究包括：(A)解开人类疾病中的组蛋白组合密码；(B)研究口腔微生物组和多细菌感染的蛋白质组学方法；(C)检测物种间的化学相互作用；(D)开发系统的乙酰组调控方法；(E)开发单抗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)发现抗生素；(I)发现蛋白质组 癌症患者药物毒性的生物标志物；以及(J)识别白内障晶状体中蛋白质-蛋白质相互作用和翻译后修饰。这些项目需要在生物医学科学家、质谱学家和来自不同机构的计算科学家参与的广泛主题上的三方合作努力。CCMS还将对来自世界各地的学生和实习科学家进行计算蛋白质组学方面的培训，并对蛋白质组学社区进行关于现代计算质谱学的教育，以鼓励其广泛采用。

DESCRIPTION: 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 col- laborative 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 in- teractions; (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 vac- cines; (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 mod- ifications 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.