Project description:In an effort to map the deeply map the structure of the genome at loci of interest, we applied Region Capture Micro-C and revealed focal patterns of contact between enhancers & promoters that we term microcompartments. We have mapped genomic structure at 0.4-1.9 Mb-sized regions at the Klf1, Ppm1g, Fbn2, Sox2, and Nanog loci across 4 conditions: wild-type and transcriptionally inhibited mouse Embryonic Stem Cells (mESCs), and cohesin-depletion & control treatments in a RAD21-AID genome-edited mESC line.
Project description:We performed Hi-C, Micro-C, and capture Micro-C in human prostate cancer cells and compared chromatin interactions called using different methods. By integrating Micro-C with NOMe-seq, ChIP-seq, and RNA-seq, we investigated the relationships among nucleosome positioning of regulatory elements, chromatin interactions, and transcription. This work provides a framework for understanding the chromatin interactions among regulatory elements, nucleosome-depleted regions, and transcription.
Project description:The research objectives is to compare vitro 3D drug sensitivity test results of micro tumor (PTC) with the clinical outcomes of patients, evaluate the consistency between the test results of the technology platform and the clinical prognosis, and explore the decision-making value and guiding significance of this technology in assisting the precise treatment of colorectal cancer. The completion of this study will provide real-world data support for the clinical application of micro tumor (PTC) in vitro 3D drug sensitivity detection technology, and provide more valuable reference basis for realizing the individualization and accuracy of colorectal cancer treatment and improving the clinical benefit rate.
Project description:Quantitative protein mapping on whole-tissue levels provides important insights into the spatially-organized regulatory processes/networks related to diseases and therapy, but remains a tremendous challenge. We describe a micro-scaffold assisted spatial proteomics(MASP) method, based on precise tissue spatial-compartmentalization using a 3D-printed micro-scaffold, capable of mapping thousands of proteins across a whole-tissue slice with excellent quantitative quality. The mapping accuracy was validated and applied in mapping >5,000 cerebral proteins in mouse brain. Under stringent cutoffs, 5019 unique proteins were mapped(N=208 micro-specimens) and 4577 proteins were mapped in all regions.
Project description:The three-dimensional (3D) organization of genome is fundamental to cell biology. To explore 3D genome, emerging high-throughput approaches have produced billions of sequencing reads, which is challenging and time-consuming to analyze. Here we present Microcket, a package for mapping and extracting interacting pairs from 3D genomics data, including Hi-C, Micro-C, and derivant protocols. Microcket utilizes a unique read-stitch strategy that takes advantage of the long read cycles in modern DNA sequencers; benchmark evaluations reveal that Microcket runs much faster than the current tools along with improved mapping efficiency, and thus shows high potential in accelerating and enhancing the biological investigations into 3D genome. Microcket is freely available at https://github.com/hellosunking/Microcket.
Project description:We report the application of in situ Hi-C technology to 40 colorectal cancer patients and 10 paired-normal tissue to identify CRC specific changes in 3D chromatin structure. The chromatin contact matrices were generated by the sequencing data and image processing/deep learning-based algorithm was proposed to identify long-range abnormal chromatin interaction patterns in the contact matrices. The tumor specific 3D chromatin structure changes and the enhancer-promoter rewiring mediated by the identified chromatin structure changes were analyzed. The complex chromosome-wide rearrangements such as chromothripsis and its effect to 3D chromatin structure were also observed.