The liver is the largest solid organ and a primary metabolic hub. In recent years, intact cell nuclei were used to perform single-nuclei RNA-seq (snRNA-seq) for tissues difficult to dissociate and for flash-frozen archived tissue samples to discover unknown and rare cell subpopulations. In this study, we performed snRNA-seq of a liver sample to identify subpopulations of cells based on nuclear transcriptomics. In 4282 single nuclei, we detected, on average, 1377 active genes and we identified seven major cell types. We integrated data from 94,286 distal interactions (p < 0.05) for 7682 promoters from a targeted chromosome conformation capture technique (HiCap) and mass spectrometry proteomics for the same liver sample. We observed a reasonable correlation between proteomics and in silico bulk snRNA-seq (r = 0.47) using tissue-independent gene-specific protein abundancy estimation factors. We specifically looked at genes of medical importance. The DPYD gene is involved in the pharmacogenetics of fluoropyrimidine toxicity and some of its variants are analyzed for clinical purposes. We identified a new putative polymorphic regulatory element, which may contribute to variation in toxicity. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and we investigated all known risk genes. We identified a complex regulatory landscape for the SLC2A2 gene with 16 candidate enhancers. Three of them harbor somatic motif breaking and other mutations in HCC in the Pan Cancer Analysis of Whole Genomes dataset and are candidates to contribute to malignancy. Our results highlight the potential of a multi-omics approach in the study of human diseases.

中文翻译：

---

肝病的多组学方法：将单核转录组学与蛋白质组学和人类肝脏中的HiCap大量数据相集成。

肝脏是最大的实体器官和主要的代谢枢纽。近年来，完整细胞核用于难解离组织和速冻存档组织样品的单核RNA-seq（snRNA-seq）的发现，以发现未知和稀有的细胞亚群。在这项研究中，我们对肝脏样品进行了snRNA-seq鉴定，以基于核转录组学鉴定细胞亚群。在4282个单核中，我们平均检测到1377个活性基因，并确定了7种主要细胞类型。我们整合了来自针对同一肝脏样品的靶向染色体构象捕获技术（HiCap）和质谱蛋白质组学的7682个启动子的94,286个远端相互作用（p <0.05）的数据。我们观察到蛋白质组学和计算机批量snRNA-seq（r = 0。47）使用独立于组织的基因特异性蛋白质丰度估算因子。我们专门研究了具有医学重要性的基因。DPYD基因参与氟嘧啶毒性的药物遗传学研究，并对其某些变体进行临床分析。我们确定了一个新的假定的多态性调控元素，可能会导致毒性变化。肝细胞癌（HCC）是最常见的原发性肝癌类型，我们调查了所有已知的风险基因。我们确定了SLC2A2基因与16个候选增强子的复杂监管格局。在全基因组全癌症分析数据集中，其中三个在HCC中具有体细胞基序断裂和其他突变，并且是导致恶性肿瘤的候选者。