Project description:To evaluate the accuracy and effectiveness of a novel screening method based on plasma multi-omics combining with artificial intelligence in a large prospective cohort for the detection of colorectal cancer and advanced adenomas.
Project description:The aim of the study is to identify differences in the global phosphoproteome across a BRCA1-deficient mouse mammary tumor panel. We have matched PARPi-naive and PARPi-resistant tumors, in which resistance was induced in vivo (mice bearing tumors were treated with PARPi untill the tumors stopped responding). Each pair of matched naive/resistant tumors originate from a different original tumor donor (one can consider each individual donor as an individual patient). From another analysis (RAD51 IRIF) we know that the mechanism of PARPi-resistance in a number of the tumors is driven by alterations in DNA damage response. Therefore, we can divide the tumors into four groups: (A) HR proficient, the exact mechanism not known, (B) HR proficient due to the loss of 53bp1 (TP53BP1), (C) HR proficient due to loss of Rev7 (MAD2L2) and (D) HR deficient, mechanism of resistance not known. Additionally, each tumor from our panel was retransplanted and challenged with 15 Gy irradiation to trigger a DNA damage response, therefore for each tumor we have an irradiated (IR) and a non-irradiated (NIR) sample. In this experiment each sample was processed in duplicate. Given all this, group (A) consists of 6 individual donors x 2 (matched naive/resistant) x 2 (NIR/IR) x 2 (duplicate) = 48 samples (samples 1-48); groups (B)-(D): 2 donors (per group) x 2 (naive/resistant) x 2 (NIR/IR) x 2 (duplicate) = 16 samples/group (B: samples 65-80, C: samples 81-96 and D: 49-64, according to the OPL label). In total this gives: 48 + 16 +16 +16 = 96 samples. Part of this analysis is used in the paper that also describes data from PXD031711
Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we apply multi-omics to comprehensively define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Integrating the chromatin-bound proteome and histone modification data sets reveals differences in the relative abundance and activities of distinct chromatin modules, identifying a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin. Single-cell approaches and human blastoid models reveal that PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, and inhibiting PRC2 promotes trophoblast fate induction and cavity formation. Our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates. Data originating from the LC-MS/MS analysis of the histone PTMs can be consulted via this project.
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: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.