An Integrative Computational Approach to Evaluate Genetic Markers for Chronic Lymphocytic Leukemia
An Integrative Computational Approach to Evaluate Genetic Markers for Chronic Lymphocytic Leukemia
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DOI：
10.1089/cmb.2017.0041
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发表时间：
2017-09
期刊：
影响因子：
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通讯作者：
Yu Zheng;Xiaoyang Li;Lydia C. Manor;Hongbao Cao;Qiusheng Chen
中科院分区：
文献类型：
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作者：
Yu Zheng;Xiaoyang Li;Lydia C. Manor;Hongbao Cao;Qiusheng Chen
最近的研究报告了数百个与慢性淋巴细胞白血病（CLL）相关的基因。然而，许多候选基因缺乏复制，结果并不总是一致。在这里，我们提出了一个计算工作流程来管理和评估 CLL 相关基因。该方法整合大规模文献知识数据、基因表达数据以及相关通路/网络信息进行定量标记评估。进行通路富集、子网络富集和基因-基因相互作用分析来研究候选基因的致病谱，为每个基因提出并验证了四个指标。通过使用我们的方法，开发了一个可扩展的 CLL 遗传数据库，包括 CLL 相关基因、通路、疾病和支持参考信息。 CLL 病例/对照分类支持了四个拟议指标的有效性，这些指标成功识别了 9 个经过充分研究的 CLL 基因（即 TNF、BCL2、TP53、VEGFA、P2RX7、AKT1、SYK、IL4 和 MDM2），并强调了两个新报告的 CLL 基因（即 PDGFRA 和 CSF1R）。本研究中开发的计算生物学方法和 CLL 数据库提供了宝贵的资源，可以促进对 CLL 遗传谱的理解。
Recent studies reported hundreds of genes linked to chronic lymphocytic leukemia (CLL). However, many of these candidate genes were lack of replication and results were not always consistent. Here, we proposed a computational workflow to curate and evaluate CLL-related genes. The method integrates large-scale literature knowledge data, gene expression data, and related pathways/network information for quantitative marker evaluation. Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analysis were conducted to study the pathogenic profile of the candidate genes, with four metrics proposed and validated for each gene. By using our approach, a scalable CLL genetic database was developed including CLL-related genes, pathways, diseases and information of supporting references. The CLL case/control classification supported the effectiveness of the four proposed metrics, which successfully identified nine well-studied CLL genes (i.e., TNF, BCL2, TP53, VEGFA, P2RX7, AKT1, SYK, IL4, and MDM2) and highlighted two newly reported CLL genes (i.e., PDGFRA and CSF1R). The computational biology approach and the CLL database developed in this study provide a valuable resource that may facilitate the understanding of the genetic profile of CLL.