Cancer Genomics Technology Development

微阵列技术的最新进展与高通量基因芯片的发展有关。 分辨率微阵列，可以映射DNA中的基因组改变和结构变异 在极高的分辨率下的拷贝数。我们在这方面应用了高分辨率阵列， 并将该技术应用于DNA酶I的定位 超敏感部位最近，我们已经证明它们可以用于绘制DNA起源图， 复制。我们还努力通过扩展样本类型来提高检测极限 福尔马林固定、石蜡包埋的样品和流式分选的原代细胞。我们有 已经证实，可以从固定的组织中获得有用的核酸制剂， 继续扩大对这种材料的分析，以用于更广泛的基因组技术。 目前的工作主要是执行下一代 测序技术。这些方法主要依赖于产生一系列DNA分子 其在测序反应期间顺序成像。我们正在调查 这些用于大RNA和小RNA的基因表达谱分析的方法，用于检测 基因组重排、突变，以及用于测量染色质修饰的DNA酶I 超敏位点和转录因子定位。这项工作的一个主要部分是 开发一个强大的计算环境，可用于分析 大量的序列数据是由这项工作产生的。虽然这是一个 具有挑战性的过程，它最终将产生一个精简的分析管道， 基于多个序列的测定将易于整合并且不受阵列平台特异性的限制。 藏物

Recent progress in microarray technology has been related to the development of high resolution microarrays which can map genomic alterations and constitutional variants in DNA copy number at an extremely high resolution. We have applied high resolution arrays in this fashion to several systems and have also adapted this technology to the mapping of DNase I hypersensitive sites. Recently, we have demonstrated that they can be used to map DNA origins of replication. We have also worked to push the limits of detection by extending sample types to formalin fixed, paraffin embedded samples and flow sorted primary cells. We have established that useful nucleic acid preparations can be obtained from fixed tissues and are continuing to extend the analysis of this material for a wider range of genomic technologies. Current efforts have been directed primarily at the implementation of next generation sequencing technologies. These methods primarily depend on producing an array of DNA molecules which are sequentially imaged during the sequencing reaction. We are investigating the use of these methods for gene expression profiling for large and small RNAs, for the detection of genome rearrangements, mutations, and for the measurement of chromatin modifications, DNase I hypersensitive sites, and transcription factor localization. A major part of this effort is the development of a powerful computational environment which can be used to analyze the massive amount of sequence data which is generated by this work. Although this is a challenging process, it ultimately will yield a streamlined analysis pipeline in which multiple sequence based assays will be easy to integrate and free of array platform specific artifacts.