Project description:Joint profiling of chromatin accessibility and gene expression from the same single cell provides critical information about cell types in a tissue and cell states during a dynamic process. These emerging multi-omics techniques help the investigation of cell-type resolved gene regulatory mechanisms. Here, we developed in situ SHERRY after ATAC-seq (ISSAAC-seq), a highly sensitive and flexible single cell multi-omics method to interrogate chromatin accessibility and gene expression from the same single cell. We demonstrated that ISSAAC-seq is sensitive and provides high quality data with orders of magnitude more features than existing methods. Using the joint profiles from thousands of nuclei from the mouse cerebral cortex, we uncovered major and rare cell types together with their cell-type specific regulatory elements and expression profiles. Finally, we revealed distinct dynamics and relationships of transcription and chromatin accessibility during an oligodendrocyte maturation trajectory.
Project description:Multi-omics molecular profiling was performed on post-radical prostatectomy material from a cohort of 132 patients with localized prostate adenocarcinoma. Unsupervised classification techniques were used to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression.
Project description:Multi-omics molecular profiling was performed on post-radical prostatectomy material from a cohort of 132 patients with localized prostate adenocarcinoma. Unsupervised classification techniques were used to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression.
Project description:Multi-omics molecular profiling was performed on post-radical prostatectomy material from a cohort of 132 patients with localized prostate adenocarcinoma. Unsupervised classification techniques were used to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression.
Project description:Multi-omics molecular profiling was performed on post-radical prostatectomy material from a cohort of 132 patients with localized prostate adenocarcinoma. Unsupervised classification techniques were used to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression.
Project description:ATAC-seq (assay for transposase-accessible chromatin followed by sequencing) is widely used to decode chromatin accessibility. Here we performed high-sensitive ATAC-seq in 9 human liver samples from normal and T2D donors, and identified a set of differentially accessible regions (DARs). DARs were overlapped with publicly available CREs databases and integrated with multi-omics data to identify candidates for further experimental validations. We identified 7 DARs that mark putative regulatory elements including a candidate enhancer for the ACOT1 gene that regulates the balance of acyl-CoA and free fatty acids in the cytoplasm. The relevance of ACOT1 regulation in T2D was supported by the analysis of transcriptomics and proteomics data in liver tissue. Conclusions: Our strategy that integrates chromatin accessibility with DNA binding and other types of omics provides novel insights towards the role of genetic regulation in complex multifactorial diseases such as T2D.
Project description:Inferring in humans biological responses to external cues such as drugs, chemicals, viruses and hormones, is an essential question in biomedicine and cannot be easily studied in humans. Thus, biomedical research has continuously relied on animal models for studying the impact of these compounds and attempted to M-^StranslateM-^T the results to humans. In this context, the Systems Biology Verification for Industrial Methodology for Process Verification in Research (SBV IMPROVER) initiative had run a Species Translation Challenge for the scientific community to explore and understand the limit of translatability from rodent to human using systems biology. Therefore, a multi-layer omics dataset was generated that comprised of phosphoproteomics, transcriptomics and cytokine data derived from normal human (NHBE) and rat (NRBE) bronchial epithelial cells exposed in parallel to more than 50 different stimuli under identical conditions. The present manuscript describes in detail the experimental settings, the generation, processing and quality control analysis of the multi-layer omics dataset. The datasets are accessible in public repositories could be leveraged for further translation studies.
Project description:Rare cells exert substantial impact on tissue physiology and pathology across a spectrum of biological realms. The elucidation of their physiological functions through multi-omics analysis is pivotal. Nonetheless, advancements in trace-level cell multi-omics technology are impeded by cellular loss during experimental procedures. Mitochondrial DNA (mtDNA) editing facilitates disease modeling of mitochondrial genetic disorders in cell lines and animals, with potential for future therapeutic applications. However, the absence of technology capable of simultaneously assessing the efficiency of mitochondrial gene editors and molecular phenotypes limits the development of mitochondrial gene editors and their in vivo therapeutic applications. Here, to address these challenges, we devised a novel omics carrier microparticle, abbreviated as OmicsCam for driving low-input cells multi-omics. OmicsCam consists of three key components: miniaturized open microparticles for multi-step biochemistry, an enlarged cell chamber boundary for streamline manipulation and minimize cell loss, and tunable permeability to ensure compatibility with key steps of magnetic separation in automated systems. By refining OmicsCam's manufacturing process, optimizing cell permeation conditions, and fine-tuning multi-omics library biochemistry, we demonstrated simultaneous assessment of mtDNA editing efficiency (mtDNA sequencing), post-editing cellular transcriptome, and chromatin accessibility in minute cell samples containing as few as 25,000 cells. Moreover, we can concurrently analyze off-target effects of gene editing. The OmicsCam platform offers a powerful way for microscale cell multi-omics analysis, enabling interrogation mitochondrial gene editing efficiency and molecular phenotypes in a unified framework. This offers a holistic perspective on the consequences of genetic manipulation within the mitochondrial genome, thereby advancing our understanding of mitochondrial biology and facilitating the development of precision therapeutics for mitochondrial disorders.