Bioinformatics

核心A的具体目标是提供信息学和统计服务，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基因变异数据库。 参与DNA修复和重组的五种酶的序列变异：NTHL 1、NEIL 1 -3和RAD 51 具体目标2预测遗传变异的功能后果：使用计算方法 以鉴定具有高概率改变的功能的种系或体细胞序列变体。 具体目标3酶动力学：通过以下方法鉴定具有改变的催化功能的序列变体： 设计和分析酶动力学实验。 特异性目的4突变谱分析：为了鉴定在哺乳动物中显示改变基因组稳定性的序列变体， 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一致，即酶家族中的缺陷， 这项研究导致了异常的碱基切除和同源性定向修复，这是驱动人类的引擎 致癌作用基因变异数据库和遗传功能后果的预测 变异（目标1-2）将用于项目1-3，以确定生化和生物化学的酶序列变异， 细胞研究这些项目将产生来自生物化学和细胞研究的数据，然后将 核心A用于评估遗传变异对催化作用的影响（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).