A5008711275- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- CAR-T cell therapy research
- Chromatography in Natural Products
- Pharmacological Effects of Natural Compounds
- Natural product bioactivities and synthesis
- Genomic variations and chromosomal abnormalities
- Medicinal Plant Pharmacodynamics Research
- Semiconductor materials and devices
- Histone Deacetylase Inhibitors Research
- Genetics and Neurodevelopmental Disorders
- Natural Language Processing Techniques
- Parallel Computing and Optimization Techniques
- Cell Image Analysis Techniques
- Superconducting Materials and Applications
- Complement system in diseases
- Simulation Techniques and Applications
- Hemoglobinopathies and Related Disorders
- Protein Degradation and Inhibitors
- Chromosomal and Genetic Variations
Fred Hutch Cancer Center
2020-2025
Hebei University of Technology
2025
Guangzhou University
2025
Wenzhou City People's Hospital
2025
The University of Texas MD Anderson Cancer Center
2024
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2024
Sichuan University
2024
West China Hospital of Sichuan University
2024
University of Wisconsin–Madison
2015-2022
Cancer Research Center
2021-2022
Abstract Background Diffuse midline gliomas (DMGs), including diffuse intrinsic pontine (DIPGs), have a dismal prognosis, with less than 2% surviving 5 years postdiagnosis. The majority of DIPGs and all DMGs harbor mutations altering the epigenetic regulatory histone tail (H3 K27M). Investigations addressing DMG epigenetics identified few promising drugs, HDAC inhibitor (HDACi) panobinostat. Here, we use clinically relevant models to identify validate other effective HDACi their biomarkers...
Single-cell high-throughput chromatin conformation capture methodologies (scHi-C) enable profiling of long-range genomic interactions. However, data from these technologies are prone to technical noise and biases that hinder downstream analysis. We develop a normalization approach, BandNorm, deep generative modeling framework, scVI-3D, account for scHi-C specific biases. In benchmarking experiments, BandNorm yields leading performances in time memory efficient manner cell-type separation,...
The development and function of stem progenitor cells that produce blood are vital in physiology. GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, acute myeloid leukemia. physiological activities necessitate it be strictly regulated, cell type-specific enhancers fulfill this role. +9.5 intronic enhancer harbors multiple conserved cis-elements, germline these cis-elements pathogenic humans. Since mechanisms...
Genome-wide hypertranscription is common in human cancer and predicts poor prognosis. To understand how might drive cancer, we applied our formalin-fixed paraffin-embedded (FFPE)–cleavage under targeted accessible chromatin method for mapping RNA polymerase II (RNAPII) genome-wide FFPE sections. We demonstrate global RNAPII elevations mouse gliomas assorted tumors small clinical samples discover regional corresponding to de novo HER2 amplifications punctuated by likely selective sweeps....
Aneuploidy is observed as gains or losses of whole chromosomes chromosome arms and a common hallmark cancer. Whereas models for the generation aneuploidy in cancer invoke mitotic errors, whole-arm might occur simply result centromere breakage. We recently showed that elevated RNA Polymerase II (RNAPII) level over S-phase-dependent histone genes predicts rapid recurrence human meningioma correlated with total relative to gains. To explain this imbalance arm gains, we have proposed...
Chronic skin ulcers, although rare, pose severe and debilitating challenges. The identification of causal metabolite biomarkers presents an opportunity to refine effective risk assessment strategies for this condition. In study, we conducted a comprehensive Two-Sample Mendelian Randomization (TSMR) investigation delineate the potential effects plasma metabolites on chronic ulcer risk. Exposure data comprised 14,296 participants with 913 from INTERVAL/EPIC-Norfolk, 8,299 1,091 309 ratios...
Current Hi-C analysis approaches are unable to account for reads that align multiple locations, and hence underestimate biological signal from repetitive regions of genomes. We developed validated mHi-C, a multi-read mapping strategy probabilistically allocate multi-reads. mHi-C exhibited superior performance over utilizing only uni-reads heuristic aimed at rescuing multi-reads on benchmarks. Specifically, increased the sequencing depth by an average 20% resulting in higher reproducibility...
Protein ensembles control genome function by establishing, maintaining, and deconstructing cell-type-specific chromosomal landscapes. A plethora of small molecules orchestrate cellular functions therefore may link physiological processes with biology. The metabolic enzyme hemoglobin cofactor heme induces proteolysis a transcriptional repressor, Bach1, regulates gene expression post-transcriptionally. However, whether controls broadly or through prescriptive actions is unclear. Using assay...
Pauses, disfluencies and language problems in Alzheimer’s disease can be naturally modeled by fine-tuning Transformer-based pre-trained models such as BERT ERNIE. Using this method with pause-encoded transcripts, we achieved 89.6% accuracy on the test set of ADReSS ( A lzheimer’s D ementia Re cognition through S pontaneous peech) Challenge. The best was obtained ERNIE, plus an encoding pauses. Robustness is a challenge for large small training sets. Ensemble over many runs BERT/ERNIE reduced...
This work concentrates on extending the utilization of multiple dual mode (MDM) counter-current chromatography in chiral separations. Two aromatic acids, 2-(6-methoxy-2-naphthyl)propionic acid (NAP) and 2-phenylpropionic (2-PPA), were enantioseparated by MDM using hydroxypropyl-β-cyclodextrin (HP-β-CD) as selector. The two-phase solvent systems consisting n-hexane/ethyl acetate 0.1 mol/L phosphate buffer pH 2.67 containing HP-β-CD (7.5:2.5:10 for NAP 7:3:10 2-PPA, v/v/v) used. Conventional...
Hypertranscription is common in human cancers and predicts poor prognosis. However detection of hypertranscription indirect, relying on accurately quantifying mRNA levels estimating cell numbers. Previously, we introduced FFPE-CUTAC, a genome-wide method for mapping RNA Polymerase II (RNAPII) formalin-fixed paraffin-embedded (FFPE) sections. Here use FFPE-CUTAC to demonstrate both transgene-driven mouse gliomas assorted tumors at active regulatory elements replication-coupled histone genes...
Abstract Several polymorphic cytochrome P‐450 and glutathione S‐transferase (GST) enzymes are involved in the activation detoxification of many potential carcinogens may therefore be important susceptibility to cancer induction. CYP1A1 Msp I, GSTM1 , GSTT1 some alleles have been correlated with an increased risk developing cancers. In present study, we examined possible associations between genetic polymorphisms colon a United Kingdom population. An excess null genotypes was observed amongst...
This tutorial is designed for processing and analyzing CUT&Tag data following the Benchtop V.3 protocol. The illustration used in this profiling of histone modifications human lymphoma K562 cell line, but generally applicable to any chromatin protein, including transcription factors, RNA polymerase II, epitope-tagged proteins. For reproducible analysis, also available on GitHub at https://yezhengstat.github.io/CUTTag_tutorial/.
Abstract CITE-seq enables paired measurement of surface protein and mRNA expression in single cells using antibodies conjugated to oligonucleotide tags. Due the high copy number molecules, sequencing antibody-derived tags (ADTs) allows for robust detection, improving cell-type identification. However, variability antibody staining leads batch effects ADT expression, obscuring biological variation, reducing interpretability, obstructing cross-study analyses. Here, we present ADTnorm (...
Recent advances in consortium-scale genome-wide association studies (GWAS) have highlighted the involvement of common genetic variants autism spectrum disorder (ASD), but our understanding their etiologic roles, especially interplay with rare variants, is incomplete. In this work, we introduce an analytical framework to quantify transmission disequilibrium genetically regulated gene expression from parents offspring. We applied conduct a transcriptome-wide study (TWAS) on 7,805 ASD...