Biologicals like anti-tumor necrosis factor (TNF) therapy for Crohn’s disease (CD) are safe and effective but there is a significant rate of primary and secondary nonresponse in the patients. In this study, we applied a computational approach to discover novel drug therapies for anti-TNF refractory CD in silico. We use a transcriptome dataset (GSE100833) for the anti-TNF refractory CD patients from NCBI GEO. After co-expression analysis, we specifically investigated the extent of protein–protein interactions among genes in clusters based on a protein–protein interaction database, STRING. Pathway analysis was performed using the clEnrich function based on KEGG gene sets. Co-expressed genes in cluster 1, 2, 3, 4, up or down-regulated genes and all differentially expressed genes are highly connected. Among them, cluster 1, which is highly enriched for chemokine signaling, also showed enrichment for cytokine–cytokine receptor interaction and identifies several drugs including cyclosporin with known efficacy in CD. Vorinostat, histone deacetylase inhibitors, and piperlongumine, which is known to have inhibitory effect on activity of NF-κB, were also identified. Some alkaloids were also selected as potential therapeutic drugs. These finding suggest that they might serve as a novel therapeutic option for anti-TNF refractory CD and support the use of public molecular data and computational approaches to discover novel therapeutic options for CD.

抗肿瘤坏死因子 (TNF) 等生物制剂治疗克罗恩病 (CD) 是安全有效的，但患者中原发性和继发性无反应的比例很高。在这项研究中，我们应用计算方法在计算机上发现抗 TNF 难治性 CD 的新药物疗法。我们使用来自 NCBI GEO 的抗 TNF 难治性 CD 患者的转录组数据集 (GSE100833)。共表达分析后，我们基于蛋白质-蛋白质相互作用数据库 STRING，专门研究了簇中基因之间蛋白质-蛋白质相互作用的程度。使用基于KEGG基因集的clEnrich函数进行通路分析。簇1、2、3、4中的共表达基因、上调或下调基因以及所有差异表达基因均高度相关。其中，趋化因子信号传导高度富集的簇 1 也表现出细胞因子-细胞因子受体相互作用的富集，并鉴定了包括环孢菌素在内的几种药物，这些药物对 CD 具有已知的功效。还鉴定出伏立诺他、组蛋白脱乙酰酶抑制剂和胡椒长明（已知对 NF-κB 活性具有抑制作用）。一些生物碱也被选为潜在的治疗药物。这些发现表明它们可能作为抗 TNF 难治性 CD 的新治疗选择，并支持使用公共分子数据和计算方法来发现 CD 的新治疗选择。