Bioinformatic Analysis of Next Generation Sequencing Data from Cancer Cells

项目摘要 这项提议支持NCI资助的两名杰出研究人员的生物信息学需求 西北大学生物化学和分子遗传学系。一个项目，与阿里博士合作 Shilatifard研究了MLL等组蛋白修饰物的突变在癌症进展中的作用。一个 最近关于突变蛋白相对于野生型的稳定性的发现揭示了 疾病和癌症治疗的新靶点。另一个项目研究转录延伸的作用。 癌症发生的因素。在白血病中，这些蛋白经常与MLL融合，但原因尚不清楚 一般的转录调控因子导致特定类型的癌症。第三个项目研究另一个染色质 蛋白质、组蛋白H3以及H3K27突变为蛋氨酸如何导致特定类型的儿科脑 癌症。在这方面，对该病分子机制的新理解也导致了一系列新的 治疗这种目前无法治愈的毁灭性儿童癌症。第四个项目是与Dr。 Marcus Peter研究了另一个基本的细胞过程，DISE，以及如何利用它来触发 细胞死亡，特别是癌细胞。所有这些项目的共同主线是需要仔细、 生物激励的计算分析，以理解下一代测序数据，即 在检查癌细胞功能时必不可少的，无论是在扰动前后。巴特姆博士将提供 这种分析，以及她在生物学和计算方面的专业知识，将使癌症生物学家能够提取更多 从他们的数据中获得洞察力，并保持高标准的科学严谨性和重复性。

Project Summary This proposal supports the bioinformatics needs of two NCI funded Outstanding Investigators at the Northwestern University Department of Biochemistry and Molecular Genetics. One project, with Dr. Ali Shilatifard, examines the role of mutations in histone modifiers such as MLL in the progression of cancer. A recent discovery on the stabilization of mutant proteins relative to wildtype gives insight into one cause of disease and a new target for cancer therapy. Another project examines the role of transcription elongation factors in cancer development. These proteins are often fused to MLL in leukemia, but it is not clear why general transcriptional regulators lead to specific types of cancer. A third project examines another chromatin protein, histone H3, and how mutation of H3K27 to methionine can lead to specific types of pediatric brain cancer. Here too, new understanding of the molecular mechanism of the disease has led to a new line of therapy for this currently incurable and devastating childhood cancer. A fourth project, in collaboration with Dr. Marcus Peter, examines another fundamental cellular process, DISE, and how it might be exploited to trigger cell death specifically in cancer cells. The common thread in all of these projects is the need for careful, biologically motivated computational analysis to make sense of next generation sequencing data that is essential in examining the function of cancer cells, both before and after perturbation. Dr. Bartom will provide this analysis, and her expertise in both biology and computation will allow cancer biologists to extract more insight from their data, and to maintain a high standard of scientific rigor and reproducibility.