A5057117181- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Metabolomics and Mass Spectrometry Studies
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Pancreatic and Hepatic Oncology Research
- Ubiquitin and proteasome pathways
- RNA regulation and disease
- Cancer-related molecular mechanisms research
- Plant-based Medicinal Research
- Biomedical Text Mining and Ontologies
- Cancer, Hypoxia, and Metabolism
- Hepatocellular Carcinoma Treatment and Prognosis
- Machine Learning in Bioinformatics
- Genomics and Phylogenetic Studies
- SARS-CoV-2 and COVID-19 Research
- DNA Repair Mechanisms
- Advanced X-ray and CT Imaging
Beijing Radiation Center
2016-2025
Academy of Military Medical Sciences
2024-2025
Anhui Medical University
2025
Peking University Shougang Hospital
2025
Huazhong University of Science and Technology
2023-2024
State Key Laboratory of Information Engineering in Surveying Mapping and Remote Sensing
2023-2024
Union Hospital
2024
Indiana University
2023
Broad Institute
2023
Union Hospital
2023
Chromatin insulators are DNA elements that regulate the level of gene expression either by preventing silencing through maintenance heterochromatin boundaries or activation blocking interactions between enhancers and promoters. CCCTC-binding factor (CTCF), a ubiquitously expressed 11-zinc-finger DNA-binding protein, is only protein implicated in establishment vertebrates. While CTCF has been diverse regulatory functions, studied limited number cell types across human genome. Thus, it not...
The vast noncoding portion of the human genome harbors a rich array functional elements and disease-causing regulatory variants. Recent high-throughput chromosome conformation capture studies have outlined principles these interacting regulating expression distal target genes through three-dimensional (3D) chromatin looping. Here we present 3DSNP, an integrated database for annotating variants by exploring their roles in interactions between elements. 3DSNP integrates 3D interactions, local...
Hi-C is commonly used to study three-dimensional genome organization. However, due the high sequencing cost and technical constraints, resolution of most datasets coarse, resulting in a loss information biological interpretability. Here we develop DeepHiC, generative adversarial network, predict high-resolution contact maps from low-coverage data. We demonstrated that DeepHiC capable reproducing data as few 1% downsampled reads. Empowered by training, our method can restore fine-grained...
Abstract As the largest substructures in nucleus, nucleoli are sites of ribosome biogenesis. Increasing evidence indicates that play a key role organization 3D genome architecture, but systematic studies nucleolus-associated chromatin interactions lacking. Here, we developed nucleolus Hi-C (nHi-C) experimental technique to enrich interactions. Using nHi-C experiment, identify 264 high-confidence domains (hNADs) form strong heterochromatin associated with and consist 24% whole HeLa cells....
CD8+ exhausted T cells (Tex) are heterogeneous. PD-1 inhibitors reinvigorate progenitor Tex, which subsequently differentiate into irresponsive terminal Tex. The ability to maintain a capacity for durable proliferation of Tex is important, but the mechanism remains unclear. Here, we showed pretreated with decitabine, low-dose DNA demethylating agent, had enhanced and effector function against tumors after anti–PD-1 treatment in vitro. Treatment decitabine plus promoted activation expansion...
Abstract Cancer is rarely the straightforward consequence of an abnormality in a single gene, but rather reflects complex interplay many genes, represented as gene modules. Here, we leverage recent advances model-agnostic interpretation approach and develop CGMega, explainable graph attention-based deep learning framework to perform cancer module dissection. CGMega outperforms current approaches prediction, it provides promising integrate multi-omics information. We apply breast cell line...
Essential genes are those whose loss of function compromises organism viability or results in profound fitness. Recent gene-editing technologies have provided new opportunities to characterize essential genes. Here, we present an integrated analysis that comprehensively and systematically elucidates the genetic regulatory characteristics human First, found act as 'hubs' protein-protein interaction networks, chromatin structure epigenetic modification. Second, represent conserved biological...
Abstract Chromatin accessibility plays important roles in revealing the regulatory networks of gene expression, while its application bladder cancer is yet to be fully elucidated. Chloride intracellular channel 3 (CLIC3) protein has been reported associated with progression some tumors, whereas specific mechanism CLIC3 tumor remains unclear. Here, we screened for key genes through identification transcription factor binding site clustered region (TFCR) on basis chromatin and TF motif. was...
Abstract Structural variations (SVs) are the greatest source of in genome and can lead to oncogenesis. However, identification interpretation SVs human cancer remain technologically challenging. Here, long‐read sequencing is first employed depict signatures structural carcinogenesis pancreatic ductal epithelium. Then widespread reprogramming 3D chromatin architecture revealed by an situ Hi‐C technique. Integrative analyses indicate that distribution pattern among highly cell‐type specific...
CCCTC-binding factor (CTCF), a ubiquitously expressed architectural protein, has emerged as key regulator of cell identity gene transcription. However, the precise molecular mechanism underlying specialized functions CTCF remains elusive. Here, we investigate through integrative analyses primary hepatocytes, myocytes, and B cells from mouse human. We demonstrate that cooperates with lineage-specific pioneer transcription factors (TFs), including MyoD, FOXA, PU.1, to control at 1D 3D levels....
Abstract CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein regulate numerous cellular processes. However, effects PTMs on genome-wide binding CTCF organization three-dimensional (3D) structure have not been fully understood. In this study, we uncovered PTM profiling demonstrated that can be O-GlcNAcylated arginine methylated....
Abstract Cyclic GMP–AMP synthase (cGAS), a cytosolic DNA sensor that initiates STING-dependent innate immune response, binds tightly to chromatin, where its catalytic activity is inhibited; however, mechanisms underlying cGAS recruitment chromatin and functions of chromatin-bound (ccGAS) remain unclear. Here we show mTORC2-mediated phosphorylation human serine 37 promotes localization in colorectal cancer cells, regulating cell growth drug resistance independently STING. We discovered ccGAS...
Abstract DNase I hypersensitive sites (DHSs) define the accessible chromatin landscape and have revolutionised discovery of distinct cis -regulatory elements in diverse organisms. Here, we report first comprehensive map human transcription factor binding site (TFBS)-clustered regions using Gaussian kernel density estimation based on genome-wide mapping TFBSs 133 cell tissue types. Approximately 1.6 million TFBS-clustered regions, collectively spanning 27.7% genome, were discovered. The TFBS...
Abstract Chemoresistance limits its clinical implementation for pancreatic ductal adenocarcinoma (PDAC). We previously generated an EGFR/HER2 targeted conjugate, dual-targeting ligand-based lidamycin (DTLL), which shows a highly potent antitumor effect. To overcome chemoresistance in PDAC, we aim to study DTLL efficacy when combined with gemcitabine and explore mechanisms of action. combination show superior inhibitory effect on the growth gemcitabine-resistant/sensitive tumors. sensitizes...
Abstract Background DNA double-strand breaks (DSBs) are among the most deleterious lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled identification of relationships between 3D chromatin structure DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions DSB formation. Results Here, we propose a framework that integrates graph neural...
Accurately measuring biological age is crucial for improving healthcare the elderly population. However, complexity of aging biology poses challenges in how to robustly estimate and interpret significance traits used estimation. Here we present SCALE, a statistical pipeline that quantifies different tissues using explainable features learned from literature single-cell transcriptomic data. Applying SCALE "Mouse Aging Cell Atlas" (Tabula Muris Senis) data, identified tissue-level programs...
The development of sequence-based deep learning methods has greatly increased our understanding how sequence determines function. In parallel, numerous interpretable algorithms have been developed to address complex tasks, such as elucidating regulatory syntax and analyzing non-coding variants from trained models. However, few studies systematically compared evaluated the performance interpretability these algorithms. Here, we introduce a comprehensive benchmark framework for evaluating...
Tandem repeat sequences (TRs), a class of repetitive genomic elements, are broadly distributed in both coding and non-coding regions. Investigating the relationship between function is essential for understanding genome. Saccharomyces cerevisiae serves as vital model organism widely used an engineered strain. Although transcriptional regulatory functions TRs promoters S.cerevisiae have been elucidated, our their roles within (CDS) remains limited. In this study, we integrate RNA-seq,...
Colorectal carcinoma (CRC) is a deadly cancer with an aggressive nature, and how CRC tumor cells manage to translocate proliferate in new tissue environment remains not fully understood. Recently, higher-order chromatin structures spatial genome organization are increasingly implicated diseases including cancer, but in-depth studies of three-dimensional (3D genome) metastatic currently lacking, preventing the understanding roles during metastasis. Here we perform multi-omics profiling...