Center for Computational Mass Spectrometry

描述：质谱法是基于将生物分子分割成更小的片段，并使用片段质量作为识别和定量生物分子的指纹。它是研究健康和病变组织中的活性分子，识别新疗法的蛋白质靶点和天然产物的主导技术。当计算质谱中心（CCMS）的最初提案于2007年提交时，缺乏足够的计算工具来分析质谱数据是主要瓶颈。在FTMS， ETD， HCD，自上而下质谱等新实验技术的应用方面取得了巨大成功，CCMS的任务仍然是开发下一代计算技术并将其应用于开放实验。在本提案中，我们将利用我们在计算蛋白质组学的不同子领域的最新成果，并将进一步扩展到以前未开发的MS应用。我们将利用6个技术研发平台，专注于蛋白质组学和基因组学技术的桥接。具体来说，我们将(a)应用蛋白质基因组学方法发现异常癌症基因并分析抗体谱；(b)天然抗生素序列；(c)通过光谱档案和网络整理光谱数据；(d)开发通用的多肽鉴定工具；(e)开发自上而下的蛋白质组学工具；(f)复用谱分析。这些技术平台是由众多生物医学合作研究推动的，使用CCMS开发的工具对他们的成功至关重要。这些研究包括(a)揭示人类疾病中的组合组蛋白密码；(b)用蛋白质基因组学方法研究口腔微生物组和多细菌感染；(c)检测种间化学相互作用；(d)发展一种对乙酰酶进行治疗性调节的系统方法；(e)开发单克隆和多克隆抗体测序工具；(f)研制乳癌疫苗；(g)临床癌症蛋白质基因组学；(h)抗生素的发现；(1)发现蛋白质组学

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.