Study on fatty liver based on Pseudotime analysis

Yunheng Wu, Meixue Li
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Abstract

In recent decades, the unhealthy diet and sedentary lifestyles of people are taking their toll on growing cases of metabolic diseases worldwide, one of them being Nonalcoholic Fatty Liver Disease (NAFLD). This disease has become one of the most sophisticated medical and physiological puzzles because of its convoluted mechanisms of progression.Existing gene expression analysis methods like microarray or RNA-sequencing are unable to resolve the complex mechanisms of progression of non-alcoholic fatty liver disease (NAFLD) due to insufficient accuracy and lack of phenotypic data. Particularly, incomplete phenotypic data in public liver gene expression cohorts have cumbered many studies on the progression of NAFLD. To address this issue, the cutting-edge pseudotime analysis is adopted to estimate liver health status in human liver gene expression data. The identified DE genes separate the NAFLD patients and the healthy controls in hierarchical clustering, and their related biological pathways are highly relevant to liver signaling and injury, implying the close relationship between the DE gene expressions and NAFLD. What's more, the pseudotime analysis we conducted simulates the deterioration of NAFLD by using liver fat percent to represent NAFLD severity and aligning the candidate samples on the estimated trajectory according to their respective gene expression and covariates; we verified the pseudotime model using another microarray cohort.
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基于伪时间分析的脂肪肝研究
近几十年来,人们不健康的饮食和久坐不动的生活方式导致世界范围内代谢性疾病的病例不断增加,其中之一是非酒精性脂肪性肝病(NAFLD)。由于其复杂的进展机制,这种疾病已成为最复杂的医学和生理学难题之一。现有的基因表达分析方法,如微阵列或rna测序,由于准确性不足和缺乏表型数据,无法解决非酒精性脂肪性肝病(NAFLD)进展的复杂机制。特别是,公共肝脏基因表达队列中不完整的表型数据阻碍了许多关于NAFLD进展的研究。为了解决这一问题,采用前沿的伪时间分析来估计人类肝脏基因表达数据中的肝脏健康状况。所鉴定的DE基因在分层聚类中将NAFLD患者与健康对照区分开,其相关生物学通路与肝脏信号和损伤高度相关,提示DE基因表达与NAFLD密切相关。更重要的是,我们进行的伪时间分析模拟了NAFLD的恶化,使用肝脏脂肪百分比代表NAFLD的严重程度,并根据各自的基因表达和协变量将候选样本对准估计的轨迹;我们使用另一个微阵列队列验证了伪时间模型。
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