Bioinformatics

核心A的具体目标是提供信息和统计服务，其中有四项： 具体目标1人类基因变异数据库：维护人类生殖系或体细胞数据库 参与DNA修复和重组的五种酶：NTHL1、NEIL1-3和RAD51的序列变异 具体目标2预测遗传变异的功能后果：使用计算方法 鉴定具有高概率功能改变的种系或体细胞序列变体。 特定目标3酶动力学：确定通过以下方式改变催化功能的序列变体 设计和分析酶动力学实验。 特指4 L产仔谱分析：鉴定具有改变基因组稳定性的序列变异体 通过分析突变谱进行细胞研究。 核心A服务与我们的中心假设的测试是一致的，即酶家族的缺陷 研究结果导致异常碱基切除和同源定向修复，这是驱动人类的引擎 致癌。基因变异数据库和基因功能后果的预测 变异(目标1-2)将被项目1-3用来确定生化和生物化学的酶序列变异 细胞研究。这些项目将从生化和细胞研究中产生数据，然后这些数据将被 核心A用来评估基因变异对催化的影响(目标3，酶动力学 分析)和基因组稳定性(目标4，突变谱分析)。

The specific aims of Core A are to provide informatics and statistics services, of which there are four: Specific Aim 1 Human gene variant database: To maintain a database of human germline or somatic sequence variation in five enzymes involved in DNA repair and recombination: NTHL1, NEIL1-3 and RAD51 Specific Aim 2 Prediction of the functional consequences of genetic variation: To use computational methods to identify germline or somatic sequence variants having, with high probability, altered function. Specific Aim 3 Enzyme kinetics: To identify sequence variants that have altered catalytic function by designing and analyzing enzyme kinetics experiments. Specific Aim 4 l\/lutation spectrum analysis: To identify sequence variants that show alter genomic stability in cellular studies by analyzing mutation spectra. Core A services are aligned with the test of our central hypothesis, that defects in the enzyme families we study result in aberrant base excision and homology-directed repair which is the engine driving human carcinogenesis. The gene variant database and predictions of the functional consequences of genetic variation (Aims 1-2) will be used by Projects 1-3 to identify enzyme sequence variants for biochemical and cellular studies. The projects will produce data from biochemical and cellular studies, which will then be used by Core A to evaluate the consequences of genetic variation for catalysis (Aim 3, Enzyme kinetics analysis) and genomic stability (Aim 4, Mutation spectrum analysis).