Project description:Subcellular organization of RNAs and proteins is critical for cell function, but we still lack global maps and conceptual frameworks for how these molecules are localized in cells and tissues. Here we introduce ATLAS-Seq, which generates transcriptomes and proteomes from detergent-free tissue lysates fractionated across a sucrose gradient. Proteomic analysis of fractions confirmed separation of subcellular compartments. Unexpectedly, RNAs tended to co-sediment with other RNAs in similar protein complexes, cellular compartments, or biological functions. With the exception of those encoding secreted proteins, most RNAs sedimented differently than their encoded protein counterparts. To identify RNA binding proteins potentially driving these patterns, we correlated their sedimentation profiles to all RNAs, confirming known interactions and predicting new associations. Hundreds of alternative RNA isoforms exhibited distinct sedimentation patterns across the gradient, despite sharing most of their coding sequence. These observations suggest that transcriptomes can be organized into networks of co-segregating mRNAs encoding functionally related proteins, and provide insights into the establishment and maintenance of subcellular organization.
Project description:We used state of the art mass spectrometry (MS) and RNA sequencing (RNA-Seq) to provide the first integrated proteomic, phosphoproteomic and transcriptomic atlas of the animal model Mus musculu . We measured 66 murine pancreatic ductal adenocarcinoma cell lines (66 proteomes and 66 phosphoproteome) and 41 healthy tissues (41 proteomes, 41 phosphoproteome, and 29 transcriptomes). The employed MS-based and bioinformatics strategy identified >17,000 proteins and >50,000 phosphorylation sites, providing expression evidence for ~76% of the 22,437 protein-coding genes reported in UniProtKB. The RNA-Seq strategy resulted in the quantification of 21,261 unique gene that were expressed in at least one of the 29 sequenced tissue.
Project description:We aimed to clarify the cell-free DNA (cfDNA) physiological role. We exposed THP1 cells to plasma from healthy individuals with and without cfDNA and compared their transcriptomes and proteomes.
Project description:Multi-omics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren’s syndrome (SS) pathology. We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Our multi-omics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.
Project description:Multi-omics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren’s syndrome (SS) pathology. We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Our multi-omics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.