Project description:we conducted integrative multiple levels of omics data including transcriptome, phosphoproteome, proteome and metabolome in different time-course of sepsis-associated liver dysfunction (SALD). This is the first trial to suggest the statistical pathway of integrative multi-omics data in sepsis. Given the increasing number of studies collecting multi-omics data but limited overview of the methodological framework for integrative analyses (Liu, Ding et al. 2013, Petersen, Zeilinger et al. 2014, Shah, Bonder et al. 2015), integrative approach in sepsis with liver dysfunction in this study will provide novel insights into the development of sepsis and ultimately offer new tools for overcoming the present diagnostic limitation. Therefore, a combined multi-omics dataset will give better accessibility of adoption in disease, and insight to identify the promising candidates for therapeutic strategies.
Project description:Intestinal organoids accurately recapitulate epithelial homeostasis in vivo, thereby representing a powerful in vitro system to investigate lineage specification and cellular differentiation. Here, we applied a multi-omics framework on stem cell-enriched and stem cell-depleted mouse intestinal organoids to obtain a holistic view of the molecular mechanisms that drive differential gene expression during adult intestinal stem cell differentiation. Our data revealed a global rewiring of the transcriptome and proteome between intestinal stem cells and enterocytes, with the majority of dynamic protein expression being transcription-driven. Integrating absolute mRNA and protein copy numbers revealed post-transcriptional regulation of gene expression. Probing the epigenetic landscape identified a large number of cell-type-specific regulatory elements, which revealed Hnf4g as a major driver of enterocyte differentiation. In summary, by applying an integrative systems biology approach, we uncovered multiple layers of gene expression regulation, which contribute to lineage specification and plasticity of the mouse small intestinal epithelium.
Project description:The pathogenesis of Colorectal cancer (CRC) metastasis remains unclear.We collect clinical data from our center and use Integrative omics to analyze and predict candidate biomarkers of colorectal cancer and distant metastasis.
Project description:Background: A pressing challenge in treating non-small cell lung cancer (NSCLC) lies in the significant variability of patient responses to immunotherapy. This issue underscores the critical need for innovative predictive models that can navigate beyond conventional biomarkers to enhance patient outcomes, particularly by addressing immunotherapy resistance or responsiveness. Hypothesis: We hypothesize that an integrated multi-omics approach will uncover interactions within the NSCLC tumor immune microenvironment (TIME) and identify novel biomarkers that are predictive of individual immunotherapy responses, thus aiding in the development of a robust personalized treatment planning model. Objective: To develop a predictive model for NSCLC immunotherapy response/resistance by identifying new biomarkers using co-detection by indexing (CODEX) and Digital Spatial Profiling of whole transcriptome atlas (DSP-WTA). Methods: We utilized a multi-omics approach, combining CODEX for spatial mapping of protein expression at the single-cell level and DSP-WTA for comprehensive transcriptomic insights from the cell types identified by CODEX. This methodology facilitated a detailed examination of the TIME in NSCLC samples from patients undergoing first-line immunotherapy. Results: Our analysis identified three cell types, proliferating tumor cells, granulocytes, and vessels, that are associated with resistance to immunotherapy. The high proportion of these cell types demonstrated a hazard ratio (HR) of 3.8 (p = 0.004) in the training cohort (N = 33) and 1.8 (p = 0.05) in the validation cohort (N = 35). In the response cell type model, higher levels of M1 macrophages, M2 macrophages, and CD4 T cells returned a HR of 0.4 (p = 0.019) in the training set and 0.49 (p = 0.036) in the validation set. Gene signatures related to these cell types also predicted outcomes with high accuracy. The resistant gene model, which included 8 genes associated with epithelial-mesenchymal transition (EMT) and cell migration showed a HR of 5.3 (p < 0.001) in the training set and 2.2 (p = 0.036) in the validation set. The response gene model, consisting of 8 genes associated with immunomodulation, had an HR of 0.22 (p = 0.005) in the training set and 0.38 (p = 0.034) in the validation set. Conclusion: This research highlights the potential of a multi-omics strategy in advancing NSCLC treatment toward precision oncology. By offering insights into the TIME and unveiling novel biomarkers, our model seeks to define resistance and to improve prediction of response to treatment.