Cancerepisys – Integrative Analysis Of Epigenetic Networks That Determine The Chronic Lymphocytic Leukemia Disease State

A public repository of data processed for Mallm, Iskar, Ishaque et. al. 2018 Linking aberrant chromatin features in chronic lymphocytic leukemia to deregulated transcription factor networks <strong>Website:</strong> http://www.cancerepisys.org/cancerepisys/index.html <strong>Github:</strong> https://github.com/CancerEpiSys/Mallm-et-al-processing-scripts <strong>Research mission</strong> <em>CancerEpiSys</em> is a BMBF funded research project with the CancerSys program that dissects the epigenetic networks associated with chronic lymphocytic leukemia (CLL) to develop novel diagnostic and therapeutic approaches for the disease. It has been initiated based on the emerging view that signals encoded in the DNA sequence, epigenetic modifications (e.g. DNA methylation, post-translational histone modifications), non-coding RNAs and nucleosome positioning are not independently regulated properties. Rather, these chromatin features are governed by an interconnected network of molecular processes that determine the cellular gene expression program. Any errors that occur in the interplay of these factors can lead to aberrant gene regulation associated with cancer. To rationalize the mode of action of novel ‘epigenetic’ drugs in cancer therapy that change properties of this network, we will dissect experimentally and mathematically the interdependence of these processes, focusing on CLL. The main objectives of <em>CancerEpiSys</em> are: (i) deciphering the relation of DNA sequence, epigenetic modifications, nucleosome positioning and aberrant gene expression in CLL, (ii) the identification of epigenetic network morphologies that describe the response to the epigenetic drugs panobinostat and 3-deazaneplanocin (DZNep) that inhibit histone deacetylases and methyltransferases, (iii) the characterization of epigenetic markers and chromatin features of CLL patient subgroups, and (iv) the integration of results into an analysis scheme for the epigenetic aberrations most relevant for prognostication, prediction of treatment relapse and stratification of patients with respect to therapeutic options. Moreover, our results will inform novel therapeutic approaches that target gene-expression programs at the epigenetic level to sensitize cancer cells towards apoptosis and anti-growth signals.本公开数据集为Mallm、Iskar、Ishaque等学者2018年发表的《将慢性淋巴细胞白血病（chronic lymphocytic leukemia, CLL）的异常染色质特征与失调的转录因子网络相关联》研究处理所得的数据资源。 <strong>网站：</strong>http://www.cancerepisys.org/cancerepisys/index.html <strong>GitHub：</strong>https://github.com/CancerEpiSys/Mallm-et-al-processing-scripts <strong>研究使命</strong> <em>癌症表观系统（CancerEpiSys）</em>是隶属于CancerSys计划、由BMBF资助的研究项目，旨在解析与慢性淋巴细胞白血病（chronic lymphocytic leukemia, CLL）相关的表观遗传网络，以开发该疾病的新型诊断与治疗手段。该项目基于新兴观点启动：DNA序列编码的信号、表观遗传修饰（epigenetic modifications，如DNA甲基化、组蛋白翻译后修饰（post-translational histone modifications））、非编码RNA（non-coding RNAs）与核小体定位（nucleosome positioning）并非独立调控的特性。相反，这些染色质特征由相互关联的分子过程网络所调控，这些过程决定了细胞的基因表达程序。这些因子之间的相互作用出现任何异常，都可能导致与癌症相关的基因调控失调。为了阐明改变该网络特性的新型“表观遗传”癌症治疗药物的作用机制，研究团队将通过实验与数学手段解析这些过程的相互依存关系，重点聚焦慢性淋巴细胞白血病（CLL）。 <em>癌症表观系统（CancerEpiSys）</em>的主要目标包括：（i）解析CLL中DNA序列、表观遗传修饰、核小体定位与异常基因表达之间的关联；（ii）识别可描述对组蛋白去乙酰化酶（histone deacetylases）与甲基转移酶（methyltransferases）抑制剂帕比司他（panobinostat）及3-脱氮腺苷（3-deazaneplanocin, DZNep）的应答的表观遗传网络形态；（iii）表征CLL患者亚群的表观遗传标志物与染色质特征；（iv）将研究结果整合为一套分析方案，用于分析与预后、治疗复发预测及患者治疗选择分层高度相关的表观遗传异常。此外，本研究的结果将为新型治疗手段提供参考，这类手段靶向表观遗传层面的基因表达程序，以增强癌细胞对凋亡与抗增殖信号的敏感性。