EXPERIMENT_TITLE: NextSeq 500 paired end sequencing
STUDY_DESCRIPTOR_STUDY_ABSTRACT: 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 sub-populations. In this study, we performed snRNA-seq of a liver sample to identify sub-populations of cells based on nuclear transcriptomics. In 4,282 single nuclei we detected on average 1,377 active genes and we identified seven major cell types. We integrated data from 94,286 distal interactions (p<0.05) for 7,682 promoters from a targeted chromosome conformation capture technique (HiCap) and mass spectrometry (MS) 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 fluoropyrimidines 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.
SAMPLE_TITLE: Human liver tissue sample from a partial hepatectomy
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "ENA-FIRST-PUBLIC", "VALUE": "2020-02-19T17:04:39Z"}, {"TAG": "ENA-LAST-UPDATE", "VALUE": "2020-02-13T12:18:01Z"}, {"TAG": "External Id", "VALUE": "SAMEA6543544"}, {"TAG": "INSDC center name", "VALUE": "UPPSALA UNIVERISTY"}, {"TAG": "INSDC first public", "VALUE": "2020-02-19T17:04:39Z"}, {"TAG": "INSDC last update", "VALUE": "2020-02-13T12:18:01Z"}, {"TAG": "INSDC status", "VALUE": "public"}, {"TAG": "Submitter Id", "VALUE": "Liver_HiCap"}, {"TAG": "common name", "VALUE": "human"}, {"TAG": "sample name", "VALUE": "Liver_HiCap"}, {"TAG": "scientific_name", "VALUE": "Homo sapiens"}, {"TAG": "tissue type", "VALUE": "Liver"}]