Layered signaling regulatory networks analysis of gene expression involved in malignant tumorigenesis of non-resolving ulcerative colitis via integration of cross-study microarray profiles.
Layered signaling regulatory networks analysis of gene expression involved in malignant tumorigenesis of non-resolving ulcerative colitis via integration of cross-study microarray profiles.
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通过整合交叉研究微阵列图谱对参与非消退性溃疡性结肠炎恶性肿瘤发生的基因表达进行分层信号调节网络分析
DOI：
10.1371/journal.pone.0067142
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Fan S;Pan Z;Geng Q;Li X;Wang Y;An Y;Xu Y;Tie L;Pan Y;Li X
背景溃疡性结肠炎（UC）是最常见的炎症性肠病（IBD），与结直肠癌的发生密切相关。到目前为止，与该疾病相关的潜在机制仍不清楚。随着微阵列基因表达谱的不断积累，基于基因调控网络的系统视角有助于更好地阐明疾病相关基因的作用。然而，微阵列数据分析的一个主要挑战是整合不同小组产生的多项研究。在本研究中，首先，我们使用经验贝叶斯（Empirical Bayes， EB）算法，通过整合交叉研究的微阵列表达数据集，模拟了与结直肠癌（CRC）发生相关的信号调节网络。其次，通过全面检索公开可用的知识库，建立了人工策划的人类癌症信号图谱。最后，人工筛选共差异表达基因来描绘分层信号调控网络。结果将重组后的信号调控网络划分为细胞外、膜、细胞质和细胞核四大层，鉴定出与结直肠癌发生相关的5个核心生物学过程和4条信号通路。因此，我们的生物学解释强调了EGF/EGFR信号通路、EPO信号通路、T细胞信号转导和BCR信号通路成员的重要性，这些信号通路负责CRC从良性UC向侵袭性UC的恶性转变。本研究为交叉研究微阵列表达数据集提供了一种标准化的归一化方法。我们的信号网络构建模型是基于实验支持的相互作用和微阵列共表达模型。基于信号通路的信号调节网络分析为结直肠癌的发生提供了指导意义，这对监测疾病进展和改善治疗干预具有重要意义。
Background Ulcerative colitis (UC) was the most frequently diagnosed inflammatory bowel disease (IBD) and closely linked to colorectal carcinogenesis. By far, the underlying mechanisms associated with the disease are still unclear. With the increasing accumulation of microarray gene expression profiles, it is profitable to gain a systematic perspective based on gene regulatory networks to better elucidate the roles of genes associated with disorders. However, a major challenge for microarray data analysis is the integration of multiple-studies generated by different groups. Methodology/Principal Findings In this study, firstly, we modeled a signaling regulatory network associated with colorectal cancer (CRC) initiation via integration of cross-study microarray expression data sets using Empirical Bayes (EB) algorithm. Secondly, a manually curated human cancer signaling map was established via comprehensive retrieval of the publicly available repositories. Finally, the co-differently-expressed genes were manually curated to portray the layered signaling regulatory networks. Results Overall, the remodeled signaling regulatory networks were separated into four major layers including extracellular, membrane, cytoplasm and nucleus, which led to the identification of five core biological processes and four signaling pathways associated with colorectal carcinogenesis. As a result, our biological interpretation highlighted the importance of EGF/EGFR signaling pathway, EPO signaling pathway, T cell signal transduction and members of the BCR signaling pathway, which were responsible for the malignant transition of CRC from the benign UC to the aggressive one. Conclusions The present study illustrated a standardized normalization approach for cross-study microarray expression data sets. Our model for signaling networks construction was based on the experimentally-supported interaction and microarray co-expression modeling. Pathway-based signaling regulatory networks analysis sketched a directive insight into colorectal carcinogenesis, which was of significant importance to monitor disease progression and improve therapeutic interventions.
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影响因子：
3.7
作者：
Andrew AS;Hu T;Gu J;Gui J;Ye Y;Marsit CJ;Kelsey KT;Schned AR;Tanyos SA;Pendleton EM;Mason RA;Morlock EV;Zens MS;Li Z;Moore JH;Wu X;Karagas MR
通讯作者：
Karagas MR
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG
溃疡性结肠炎。
DOI：
10.1016/s0140-6736(16)32126-2
发表时间：
2017-04-29
期刊：
Lancet (London, England)
影响因子：
--
作者：
Ungaro R;Mehandru S;Allen PB;Peyrin-Biroulet L;Colombel JF
通讯作者：
Colombel JF
影响因子：
3
作者：
Bader, GD;Hogue, CW
通讯作者：
Hogue, CW
影响因子：
5.8
作者：
Barsky, Aaron;Gardy, Jennifer L.;Munzner, Tamara
通讯作者：
Munzner, Tamara