Tracing clonal evolution via transcriptome changes and somatic mutations (A15)

我们将开发计算方法来确定AML患者样本的克隆结构，并将该克隆结构与单细胞基因表达谱联系起来。此外，我们将开发一种方法来定量比较克隆和细胞类型之间的表达差异。有了这些手头的新工具，我们就能够检验表观遗传修饰基因DNMT3A和TET2突变导致表观遗传突变子表型的假设。为此，我们将分析由于细胞系和患者样本中的这些突变而导致的表达差异的变化。

We will develop computational methods to determine the clonal structure of AML patient samples and link this clonal structure to single cell gene expression profiles. Furthermore, we will develop a method to quantitatively compare expression variance between clones and cell types. With those novel tools at hand we are then able to test the hypothesis that mutations in the epigenetic modifier genes DNMT3A and TET2 lead to an epigenetic mutator phenotype. To this end, we will analyse changes in expression variance due to those mutations in a cell line and in patient samples.