Project description:We used a multi-omics approach in an attempt to identify mechanisms driving the transcriptional abnormalities in peripheral blood CD4+ T cells of children with active JIA. We demonstrate that active JIA is associated with distinct alterations in CD4+ T cell chromatin, as assessed by ATAC-seq studies. However, 3D chromatin architecture, assessed by HiChIP and simultaneous mapping of CTCF anchors of chromatin loops, reveals that normal 3D chromatin architecture is largely preserved in JIA CD4+ T cells. However, overlapping CTCF binding, ATACseq, and RNAseq data with known JIA genetic risk loci demonstrated the presence of genetic influences on the observed transcriptional abnormalities and identified candidate target genes. These studies demonstrate the utility of multi-omics approaches for unraveling some of the most vexing questions regarding the pathobiology of autoimmune diseases.
Project description:We used a multi-omics approach in an attempt to identify mechanisms driving the transcriptional abnormalities in peripheral blood CD4+ T cells of children with active JIA. We demonstrate that active JIA is associated with distinct alterations in CD4+ T cell chromatin, as assessed by ATAC-seq studies. However, 3D chromatin architecture, assessed by HiChIP and simultaneous mapping of CTCF anchors of chromatin loops, reveals that normal 3D chromatin architecture is largely preserved in JIA CD4+ T cells. However, overlapping CTCF binding, ATACseq, and RNAseq data with known JIA genetic risk loci demonstrated the presence of genetic influences on the observed transcriptional abnormalities and identified candidate target genes. These studies demonstrate the utility of multi-omics approaches for unraveling some of the most vexing questions regarding the pathobiology of autoimmune diseases.
Project description:Investigation of lung adenocarcinoma (LUAD) and breast cancer cells cultured in either a nutrient-rich or -restricted culture conditions trough a multi-omics approach, including transcriptomics, to explore the molecular changes underlying the transition from 2D to 3D cultures.
Project description:We used a multi-omics approach in an attempt to identify mechanisms driving the transcriptional abnormalities in peripheral blood CD4+ T cells of children with active JIA. We demonstrate that active JIA is associated with distinct alterations in CD4+ T cell chromatin, as assessed by ATAC-seq studies. However, 3D chromatin architecture, assessed by HiChIP and simultaneous mapping of CTCF anchors of chromatin loops, reveals that normal 3D chromatin architecture is largely preserved in JIA CD4+ T cells. However, overlapping CTCF binding, ATACseq, and RNAseq data with known JIA genetic risk loci demonstrated the presence of genetic influences on the observed transcriptional abnormalities and identified candidate target genes. These studies demonstrate the utility of multi-omics approaches for unraveling some of the most vexing questions regarding the pathobiology of autoimmune diseases.
Project description:Relapse remains a determinant of treatment failure and contributes significantly to mortality in acute myeloid leukemia (AML) patients. Despite efforts to understand AML progression and relapse mechanisms, findings on acquired gene mutations in relapse vary, suggesting inherent genetic heterogeneity and emphasizing the role of epigenetic modifications. Herein, we characterized genetic and epigenetic changes in AML progression using multi-omics approaches to elucidate the underlying mechanisms of relapse. Differential interaction analysis showed significant 3D chromatin landscape reorganization between relapse and diagnosis samples. Comparing global open chromatin profiles revealed that relapse samples had significantly fewer accessible chromatin regions than diagnosis samples. In addition, we discovered that relapse-related upregulation was achieved either by forming new active enhancer contacts or by losing interactions with poised enhancers/potential silencers. Altogether, our study highlights the impact of genetic and epigenetic changes on AML progression, underlining the importance of multi-omics approaches in understanding disease relapse mechanisms and guiding potential therapeutic interventions.
Project description:Understanding the molecular underpinnings of adipogenesis is of fundamental importance for the development of novel therapeutics against metabolic disorders. However, translational approaches are hampered as current models do not accurately recapitulate adipogenesis. Here, a scaffold-free versatile 3D adipocyte culture platform with chemically defined conditions is presented in which primary human preadipocytes accurately recapitulate adipogenesis. Following differentiation, multi-omics profiling and functional tests demonstrate that 3D adipocyte cultures feature mature molecular and cellular phenotypes similar to freshly isolated mature adipocytes. Spheroids exhibit physiologically relevant gene expression signatures with 4704 differentially expressed genes compared to conventional 2D cultures (false discovery rate < 0.05), including the concerted expression of factors shaping the adipogenic niche. Furthermore, lipid profiles of >1000 lipid species closely resemble patterns of the corresponding isogenic mature adipocytes in vivo (R^2 = 0.97). Integration of multi-omics signatures with analyses of the activity profiles of 503 transcription factors using global promoter motif inference reveals a complex signaling network, involving YAP, Hedgehog, and TGFβ signaling, that links the organotypic microenvironment in 3D culture to the activation and reinforcement of PPARγ and CEBP activity resulting in improved adipogenesis.
Project description:We combine state-of-the-art data acquisition platforms and bioinformatics tools to devise PAMAF, a workflow that simultaneously examines twelve omics modalities, i.e., protein abundance from whole-cells, nucleus, exosomes, secretome and membrane; N-glycosylation, phosphorylation; metabolites; mRNA, miRNA; and, in parallel, single-cell transcriptomes. Here we apply PAMAF in an established in vitro model of TGFβ-induced epithelial to mesenchymal transition (EMT) to quantify >61,000 molecules from 12 omics and 10 timepoints over 12 days. Bioinformatics analysis of this EMT-ExMap resource allowed us to identify; –unexpected topological coupling between omics, –four distinct cell states during EMT (E, E/M-1, E/M-2, M), –omics-specific kinetic paths, –stage-specific multi-omics characteristics, –distinct regulatory classes of genes, –ligand–receptor mediated intercellular crosstalk using an innovative pipeline integrating scRNAseq and subcellular proteomics, and –novel combinatorial drug targets (e.g., Hedgehog signaling and CAMK-II) to inhibit EMT, which we validate using a 3D mammary duct-on-a-chip platform. Overall, while this study provides an unprecedented resource on TGFβ signaling and EMT, PAMAF-like workflows can be applied to generate comprehensive molecular landscapes of other multifaceted biological processes.
Project description:We use Saccharomyces cerevisiae to perform absolute quantitative multi-omics analysis to map interactions of different cellular processes during the yeast cell cycle.
Project description:Florida’s coral reefs are currently experiencing a multi-year disease-related mortality event, that has resulted in massive die-offs in multiple coral species. Coral monitoring data and disease prevention/treatment efforts from recent years have identified individual Orbicella faveolata that possess high, moderate, or low resistance to stony coral tissue loss disease (SCTLD). Ninety samples of high, moderate, or low SCTLD resistance were collected from 3 reefs for bottom-up LC-MS/MS analysis (n=30 for each resistance category).