A Multi-Omics Approach to Liver Diseases: Integration of Single Nuclei Transcriptomics with Proteomics and HiCap Bulk Data in Human Liver
| العنوان: | A Multi-Omics Approach to Liver Diseases: Integration of Single Nuclei Transcriptomics with Proteomics and HiCap Bulk Data in Human Liver |
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| المؤلفون: | Cavalli, M., Diamanti, K., Pan, G., Spalinskas, Rapolas, Dr., 1983, Kumar, C., Deshmukh, A. S., Mann, M., Sahlén, Pelin, Komorowski, J., Wadelius, C. |
| المصدر: | Omics. 24(4):180-194 |
| مصطلحات موضوعية: | human liver, multi-omics data integration, proteomics, snRNA-seq, ADAMTS protein, ADAMTS2 protein, albumin, biological marker, cadherin, cadherin 11, CD163 antigen, CD74 antigen, collagen type 3, collagen type 6, cystic fibrosis transmembrane conductance regulator, dihydropyrimidine dehydrogenase, epithelial cell adhesion molecule, fibroblast growth factor 1, fluorouracil, glucose transporter 1, glucose transporter 2, interleukin 18, messenger RNA, nostrin, proteome, small nuclear RNA, somatomedin binding protein 3, transcription factor Sox4, transcription factor Sox9, transcriptome, unclassified drug, vasculotropin receptor 1, apoa2 gene, Article, c3 gene, controlled study, dcn gene, enhancer region, eps2 gene, f5 gene, f8 gene, fgb gene, fgl1 gene, g6pc gene, gene, gene identification, human, human cell, human chromosome, human tissue, intron, lamb1 gene, liver cell carcinoma, liver parenchyma, lrp2 gene, marker gene, mass spectrometry, multiomics, mup3 gene, myo1f gene, oit3 gene, pck1 gene, plekhg1 gene, plg gene, priority journal, promoter region, ptprb gene, RNA conformation, RNA sequencing, single nucleotide polymorphism, spp1 gene, transcriptomics |
| الوصف: | 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. |
| وصف الملف: | |
| الوصول الحر: | https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-277233Test https://doi.org/10.1089/omi.2019.0215Test |
| قاعدة البيانات: | SwePub |
| تدمد: | 15362310 15578100 |
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| DOI: | 10.1089/omi.2019.0215 |