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HBV感染后肝癌的转化基因组学研究
焦亡相关基因的基因体甲基化水平改变可作为肝癌液体活检方案中的标志物。Zhang H, Dong P, Fan H, Liang H, Zhang K, Zhao Y, Guo S, Schrodi SJ, Fan Y, Zhang D. Gene body hypomethylation of pyroptosis-related genes NLRP7, NLRP2, and NLRP3 facilitate non-invasive surveillance of hepatocellular carcinoma. Functional & Integrative Genomics. 2023 Jun;23(2):198.
肝脏穿刺组织中的HBV-宿主整合谱提示抗病毒治疗可以改变肝脏内病毒整合事件的积累，降低病毒整合对于肝癌发生的风险。Zhang M, Zhang H, Cheng X, Wang X, Xu H, Gao X, Wu R, Zhang D, Xia Y, Niu J. Liver biopsy of chronic hepatitis B patients indicates HBV integration profile may complicate the endpoint and effect of entecavir treatment. Antiviral Research. 2022 Aug 1;204:105363.
HBV-肝细胞互作中的基因组DNA甲基化在病理改变和肿瘤发生中的作用。Zhang D$, Guo S, Schrodi SJ$. Mechanisms of DNA Methylation in Virus-Host Interaction in Hepatitis B Infection: Pathogenesis and Oncogenetic Properties. International Journal of Molecular Sciences. 2021; 22(18)
HBV-人基因组DNA整合的高通量测序方案以及病毒整合相关功能改变。Zhang D$, Zhang K, Protzer U, Zeng C. HBV Integration Induces Complex Interactions between Host and Viral Genomic Functions at the Insertion Site. J Clin Transl Hepatol 2021, 9(3): 399-408.
在cfDNA全基因组甲基化分析中，确定特定基因组区域在低重数覆盖度下对肝癌患者的预测性能可以达到全基因组较高测序通量时的同等水平，可以有效降低cfDNA测序量的需求，使基于cfDNA甲基化的肝癌筛查技术有了更广临床应用的可能以及在为相关研究中以较低成本进行cfDNA甲基化分析提供了解决思路。Zhang H, Dong P, Guo S, Tao C, Chen W, Zhao W, Wang J, Cheung R, Villanueva A, Fan J, Ding H, Schrodi S. J, Zhang D$ and Zeng C$. Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing. BMC Med.2020;18(1):200.
基于外周血病毒-宿主整合片断捕获技术的HBV感染后肝癌预警方案，也可成为靶向病毒整合蛋白免疫治疗方案的辅助评价工具。Chen W*, Zhang K*, Dong P*, Fanning G, Tao C, Zhang H, Guo S, Wang Z, Hong Y, Yang X, Lai S, Ding H, Zhao H, Zeng C$, Protzer U$, Zhang D$. Noninvasive chimeric DNA profiling identifies tumor-originated HBV integrants contributing to viral antigen expression in liver cancer. Hepatol Int.2020;14(3):326-337.
肿瘤表观遗传学与生物标志物
泛癌前揭示不同组织从癌前阶段向肿瘤阶段演化中DNA甲基化特征性改变的组织特异性。Zhang F, Zhang X, Zhang H, Lin D, Fan H, Guo S, An F, Zhao Y, Li J$, Schrodi SJ$, Zhang D$. Pan-precancer and cancer DNA methylation profiles revealed significant tissue specificity of interrupted biological processes in tumorigenesis. Epigenetics. 2023 Dec 31;18(1):2231222.
高低级别腺瘤全基因组甲基化谱揭示肿瘤基因组中特定位点的甲基化水平改变可以追溯至良性腺瘤的早期阶段，可作为结直肠癌早诊的标志物。Fan J, Li J, Guo S, Tao C, Zhang H, Wang W, Zhang Y, Zhang D$, Ding S$ and Zeng C$.Genome-wide DNA methylation profiles of low- and high-grade adenoma reveals potential biomarkers for early detection of colorectal carcinoma.Clin Epigenetics.2020;12(1):56.
人类疾病的转化基因组学研究
肥厚型心肌病患者的DNA甲基化谱特征改变揭示心肌内的电生理和免疫失调是最关键的病理改变。Li X, Fan H, Song X, Song B, Liu W, Dong R, Zhang H, Guo S, Liang H, Schrodi SJ, Fu X, Kaushal S, Ren Y$, Zhang D$. DNA methylome and transcriptome profiling reveal key electrophysiology and immune dysregulation in hypertrophic cardiomyopathy. Epigenetics. 2023;18(1):2195307.
健康个体多组织后合子突变深度分析发现胚胎发育早期缺氧可在个体基因组中留下特征标记。Hong Y*, Zhang D*, Zhou X*, Chen A*, Abliz A*, Bai J, Wang L, Hu Q, Gong K, Guan X, Liu M, Zheng X, Lai S, Qu H, Zhao F, Hao S, Wu Z, Cai H, Hu S, Ma Y, Zhang J, Ke Y, Wang Q-f, Chen W$, Zeng C$. Common Postzygotic Mutational Signatures in Healthy Adult Tissues Related to Embryonic Hypoxia. Genomics, Proteomics & Bioinformatics. 2021
在高度近视人群中分析全部已知KEGG通路中的微效单核苷酸多态位点对疾病发生的贡献，在3个独立近视人群队列中检验多态显著富集的通路，为合作单位提出近视发生中“巩膜缺氧微环境是诱导巩膜成纤维细胞向肌成纤维细胞分化，导致细胞外基质重塑”的分子机制提供了遗传学证据。Zhao F*, Zhang D*, Zhou Q, Zhao F, He M, Yang Z, Su Y, Zhai Y, Yan J, Zhang G, Xue A, Tang J, Han X, Shi Y, Zhu Y, Liu T, Zhuang W, Huang L, Hong Y, Wu D, Li Y, Lu Q, Chen W, Jiao S, Wang Q, Srinivasalu N, Wen Y, Zeng C, Qu J$ and Zhou X$. Scleral HIF-1alpha is a prominent regulatory candidate for genetic and environmental interactions in human myopia pathogenesis. EBioMedicine. 2020;57.102878.
宏基因组学
通过Shotgun Sequencing技术，在国际上首次对睑板腺功能障碍患者的睑脂、结膜表面、眼睑皮肤的菌群进行了全基因组分析，发现腺体内的菌群出现复杂的代谢变化，其中的致病菌数量减少，菌群的复杂度降低，但一些致病菌的检出率显著提高。Zhao F*, Zhang D*, Ge C, Zhang L, Reinach P. S, Tian X, Tao C, Zhao Z, Zhao C, Fu W, Zeng C and Chen W. Metagenomic Profiling of Ocular Surface Microbiome Changes in Meibomian Gland Dysfunction. Invest Ophthalmol Vis Sci.2020;61(8):22.
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