捻转血矛线虫阿苯达唑敏感株和耐药株比较转录组学分析

Comparative Transcriptome Analysis of Albendazole-susceptible and Resistant Strains of Haemonchus contortus by RNA-Seq

为探明捻转血矛线虫阿苯达唑敏感株和耐药株在转录组水平的差异,挖掘耐药相关基因,本研究采用Illumina HiSeq 4000对敏感虫株和耐药虫株进行转录组测序,构建cDNA文库,通过质控后,对其进行生物信息学分析。结果显示:敏感和耐药虫株相比较共获得218个显著(P≤0.05)差异表达基因,对显著差异表达基因进行GO功能富集,有121、82和102个基因分别注释到生物学过程、细胞组分和分子功能三大类的206个GO terms上。KEGG数据库分析显示,有42个显著差异表达基因参与31条KEGG信号通路,显著富集在药物代谢-细胞色素P450、药物代谢-其他酶等通路。在敏感株和耐药株中,筛选出GST、CYPs和UGT等9个耐药相关基因,这些基因在捻转血矛线虫耐药中发挥重要的作用。本研究利用RNA-Seq预测出敏感虫株和耐药虫株差异表达基因在功能分类和代谢通路等方面的生物学特征,挖掘出耐药相关基因,进一步为捻转血矛线虫药物靶点预测及耐药性早期鉴别诊断的建立提供重要基础。

To explore the differences in transcriptome levels between Haemonchus contortus albendazole sensitive and resistant strains, and to find out drug resistance-related genes. Samples of susceptible and resistant strains were analyzed using Illumina HiSeq 4000 platform and their transcriptome libraries were constructed. After quality filtering, bioinformatics analysis was carried out. The results showed that:A total of 218 significantly different expressed genes(DEGs) between albendazole-susceptible and resistant strains were obtained. Among these 218 genes, 121,82 and 102 DEGs have been annotated to 206 GO terms of three categories respectively, namely biological process, cellular component and molecular function. KEGG analysis showed that 42 significantly DEGs were involved in 31 KEGG pathways, and clustered significantly in pathways of drug metabolism-cytochrome P450, drug metabolism-other enzymes and so on. In addition, we identified 9 drug resistance genes in susceptible and resistant strains, such as GST, CYPs, UGT and so on, which play an important role in the drug resistance of Haemonchus contortus. In this study, the biological characteristics of DEGs in susceptible and resistant strains were predicted by RNA-Seq, which involved functional classification and metabolic pathways. This study provides a foundation for drug target prediction and the establishment of early differential diagnosis methods for drug resistance provides an important basis.