Center for Computational Mass-Spectrometry

该申请寻求对计算质谱学卓越中心和国家 在蛋白质组学的广泛领域的国际资源。建议扩大现有研究 活动，分支到以前未开发的领域的计算蛋白质组学，并支持多个 合作努力。该提案解决了影响整个 蛋白质组学社区和损害解释的数据在数以千计的实验室在世界各地。 我们的目标是将现代算法技术引入质谱分析，并建立一个新的 生成可靠的开放获取软件工具，以支持质谱分析的新发展 仪器和质谱的新兴应用。该建议侧重于四个方面 方向：（i）实现复杂的质谱搜索，（ii）分析未知的蛋白质组， 蛋白质数据库，（iii）分析改变的蛋白质组，和（iv）构建蛋白质基因组注释， 分析路径。这些方向涵盖了研究充分但仍未充分解决的问题 (like寻找突变和翻译后修饰）和未探索的问题， 目前没有可用的计算工具（如抗体测序或分析癌症中的融合蛋白）。 这些项目需要在涉及生物医学和生物技术的广泛主题上进行双向合作， 来自不同机构的计算机科学家。虽然许多合作已经建立， 在圣地亚哥（加州大学圣地亚哥分校和伯纳姆研究所），其他16所美国大学，医院和生物技术 公司以及德国、新加坡、西班牙、瑞典和美国的外国研究机构 王国，我们建议通过开发强大的开放获取质量来进一步扩展这些合作 光谱分析软件，将促进实验和计算之间的交流 蛋白质组学的研究人员这些合作项目中涉及的生物医学应用包括， 不限于（i）发现癌症生物标志物，（ii）阐明老年白内障透镜的变化，（iii） 了解细菌如何适应抗生素和其他恶劣条件，（iv）解决需要， 不断重新配制流感疫苗，使其有效，以及（v）蛇毒的测序， 在凝血药物的设计中发挥了重要作用。计算机领域的教育活动 蛋白质组学也将发展，包括短期课程，研讨会计划，年度会议， 学生和博士后的协调教育。

This application seeks support for a center of excellence in computational mass spectrometry and a national and international resource in the broad area of proteomics. It proposes to enlarge the current research activities, to branch into previously unexplored areas of computational proteomics, and to support multiple collaborative efforts. The proposal addresses the computational bottleneck that affects the entire proteomics community and impairs interpretation of data in thousands of experimental labs around the world. The goal is to bring the modern algorithmic technologies to mass-spectrometry and to build a new generation of reliable open access software tools to support both new development in mass-spectrometry instrumentation and the emerging applications of mass-spectrometry. The proposal focuses on four directions: (i) enabling complex mass spectrometry searches, (ii) analyzing unknown proteomes without protein databases, (iii) analyzing altered proteomes, and (iv) constructing proteogenomic annotations and analyzing pathways. These directions cover both well-studied but still inadequately addressed problems (like search for mutations and post-translational modifications) and unexplored problems for which there are no computational tools currently available (like antibody sequencing or analyzing fusion proteins in cancer). These projects require two-way collaborative efforts on a wide range of topics involving biomedical and computational scientists from various institutions. While many collaborations have been already established at San Diego (UCSD and Burnham Institute), sixteen other US universities, hospitals and biotechnology companies, as well as foreign research institutions at Germany, Singapore, Spain, Sweden, and United Kingdom, we propose to further extend these collaborations by developing robust open access mass spectrometry software that will catalyze the exchanges between experimental and computational researchers in proteomics. The biomedical applications addressed in these collaborative projects include but are not limited to (i) discovery of cancer biomarkers, (ii) elucidation of changes in aged cataractous lens, (iii) understanding how bacteria adjust to antibiotics and other harsh conditions, (iv) addressing the need to constantly reformulate the influenza vaccine to make it efficient, and (v) sequencing of snake venoms that proved instrumental in design of blood clotting drugs. Educational activities in the area of computational proteomics will also be developed, including short courses, a seminar program, an annual conference, and concerted education of students and postdocs.