A5068072367- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Gene Regulatory Network Analysis
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Image Analysis Techniques
- Bioinformatics and Genomic Networks
- Computational Drug Discovery Methods
- Gene expression and cancer classification
- Cancer Genomics and Diagnostics
- Plant-Microbe Interactions and Immunity
- Inflammatory mediators and NSAID effects
- MicroRNA in disease regulation
- Immune cells in cancer
- Molecular Biology Techniques and Applications
- Plant Pathogenic Bacteria Studies
- Human Mobility and Location-Based Analysis
- Education Practices and Challenges
- Salivary Gland Tumors Diagnosis and Treatment
- Data-Driven Disease Surveillance
- Salivary Gland Disorders and Functions
- Seismology and Earthquake Studies
Salk Institute for Biological Studies
2017-2025
University of California, San Diego
2017-2025
Palo Alto Institute
2024-2025
Arc Research Institute
2024-2025
Beijing Institute of Technology
2024
University of Science and Technology of China
2024
La Jolla Alcohol Research
2023
Beijing Normal University
2022
Tsinghua University
2015-2018
The emergence of large-scale genomic, chemical and pharmacological data provides new opportunities for drug discovery repositioning. In this work, we develop a computational pipeline, called DTINet, to predict novel drug-target interactions from constructed heterogeneous network, which integrates diverse drug-related information. DTINet focuses on learning low-dimensional vector representation features, accurately explains the topological properties individual nodes in then makes prediction...
Methylation and the single neuronal cell The presence or absence of methylation on chromosomal DNA can drive repress gene expression. Now, a comprehensive map variation in populations, including between-species comparison, illustrates how epigenetic diversity plays important roles development. Luo et al. examined is both similar different within neurons at single-nucleus level humans mice. They identified 16 mouse 21 human clusters, with greater complexity excitatory deep brain layers than...
Here we report the generation of a multimodal cell census and atlas mammalian primary motor cortex as initial product BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved morphological electrophysiological properties cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance collective knowledge...
RNA-binding proteins (RBPs) play important roles in the post-transcriptional control of RNAs. Identifying RBP binding sites and characterizing preferences are key steps toward understanding basic mechanisms gene regulation. Though numerous computational methods have been developed for modeling preferences, discovering a complete structural representation targets by integrating their available features all three dimensions is still challenging task. In this paper, we develop general flexible...
Abstract Mammalian brain cells show remarkable diversity in gene expression, anatomy and function, yet the regulatory DNA landscape underlying this extensive heterogeneity is poorly understood. Here we carry out a comprehensive assessment of epigenomes mouse cell types by applying single-nucleus methylation sequencing 1,2 to profile 103,982 nuclei (including 95,815 neurons 8,167 non-neuronal cells) from 45 regions cortex, hippocampus, striatum, pallidum olfactory areas. We identified 161...
Abstract Single-cell DNA methylome profiling has enabled the study of epigenomic heterogeneity in complex tissues and during cellular reprogramming. However, broader applications method have been impeded by modest quality sequencing libraries. Here we report snmC-seq2, which provides improved read mapping, reduced artifactual reads, enhanced throughput, as well increased library complexity coverage uniformity compared to snmC-seq. snmC-seq2 is an efficient strategy suited for large-scale...
Three-dimensional genome structure plays a pivotal role in gene regulation and cellular function. Single-cell analysis of architecture has been achieved using imaging chromatin conformation capture methods such as Hi-C. To study variation chromosome between different cell types, computational approaches are needed that can utilize sparse heterogeneous single-cell Hi-C data. However, few exist able to accurately efficiently cluster data into constituent types. Here, we describe scHiCluster,...
Single-cell technologies measure unique cellular signatures but are typically limited to a single modality. Computational approaches allow the fusion of diverse single-cell data types, their efficacy is difficult validate in absence authentic multi-omic measurements. To comprehensively assess molecular phenotypes cells, we devised single-nucleus methylcytosine, chromatin accessibility, and transcriptome sequencing (snmCAT-seq) applied it postmortem human frontal cortex tissue. We developed...
Delineating the gene-regulatory programs underlying complex cell types is fundamental for understanding brain function in health and disease. Here, we comprehensively examined human epigenomes by probing DNA methylation chromatin conformation at single-cell resolution 517 thousand cells (399 neurons 118 non-neurons) from 46 regions of three adult male brains. We identified 188 characterized their molecular signatures. Integrative analyses revealed concordant changes methylation,...
Cytosine DNA methylation is essential in brain development and implicated various neurological disorders. Understanding diversity across the entire a spatial context fundamental for complete molecular atlas of cell types their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) multi-omic (snm3C-seq)
Abstract Plant leaf intercellular space provides a nutrient-rich and heterogeneous niche for microbes that critically impacts plant health. However, how individual cells respond to microbial colonization remains largely elusive. Here, by time-resolved simultaneous single-cell transcriptome epigenome profiling of plants ( Arabidopsis thaliana ) infected virulent avirulent bacterial pathogens Pseudomonas syringae ), we present cell atlases with gene regulatory logic involving transcription...
Abstract The proliferation of single-cell RNA-sequencing data has led to the widespread use cellular deconvolution, aiding extraction cell-type-specific information from extensive bulk data. However, those advances have been mostly limited transcriptomic With recent developments in DNA methylation (scDNAm), there are emerging opportunities for deconvolving DNAm data, particularly solid tissues like brain that lack cell-type references. Due technical limitations, current scDNAm sequences...
Abstract Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution characterization of type diversity the brain 1 , neuronal often studied out context anatomical properties. To improve our understanding relationship between features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing link neural epigenomic...
Abstract Divergence of cis- regulatory elements drives species-specific traits 1 , but how this manifests in the evolution neocortex at molecular and cellular level remains unclear. Here we investigated gene programs primary motor cortex human, macaque, marmoset mouse using single-cell multiomics assays, generating expression, chromatin accessibility, DNA methylome chromosomal conformation profiles from a total over 200,000 cells. From these data, show evidence that divergence transcription...
Abstract Recent advances in single-cell technologies have led to the discovery of thousands brain cell types; however, our understanding gene regulatory programs these types is far from complete 1–4 . Here we report a comprehensive atlas candidate cis -regulatory DNA elements (cCREs) adult mouse brain, generated by analysing chromatin accessibility 2.3 million individual cells 117 anatomical dissections. The includes approximately 1 cCREs and their across 1,482 distinct populations, adding...
Abstract Single-cell analyses parse the brain’s billions of neurons into thousands ‘cell-type’ clusters residing in different brain structures 1 . Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific types. Here we used epi-retro-seq 2 to link single-cell epigenomes and for 33,034 dissected from 32 regions projecting 24 targets (225 source-to-target combinations) across whole mouse brain. We highlight uses these data...
Abstract Plants lack specialized and mobile immune cells. Consequently, any cell type that encounters pathogens must mount responses communicate with surrounding cells for successful defence. However, the diversity, spatial organization function of cellular states in pathogen-infected plants are poorly understood 1 . Here we infect Arabidopsis thaliana leaves bacterial trigger or supress integrate time-resolved single-cell transcriptomic, epigenomic transcriptomic data to identify states. We...
The human hippocampus and prefrontal cortex play critical roles in learning cognition
Abstract Cellular organization is central to tissue function and homeostasis, influencing development, disease progression, therapeutic outcomes. The emergence of spatial omics technologies, including transcriptomics proteomics, has enabled the integration molecular histological features within tissues. Analyzing these multimodal data presents unique challenges, variable resolutions, imperfect alignment, limited or coverage. To address issues, we introduce CORAL, a probabilistic deep...
Higher-order chromatin structure and DNA methylation are critical for gene regulation, but how these vary across the human body remains unclear. We performed multi-omic profiling of 3D genome 86,689 single nuclei 16 tissues, identifying 35 major 206 cell subtypes. revealed extensive changes in CG non-CG almost all types characterized at an unprecedented cellular resolution. Intriguingly, discrepancies exist between delineated by structure, indicating that role distinct epigenomic features...
Abstract The emergence of large-scale genomic, chemical and pharmacological data provides new opportunities for drug discovery repositioning. Systematic integration these heterogeneous not only serves as a promising tool identifying drug-target interactions (DTIs), which is an important step in development, but also more complete understanding the molecular mechanisms action. In this work, we integrate diverse drug-related information, including drugs, proteins, diseases side-effects,...
Cytosine DNA methylation is essential in brain development and has been implicated various neurological disorders. A comprehensive understanding of diversity across the entire context brain's 3D spatial organization for building a complete molecular atlas cell types their gene regulatory landscapes. To this end, we employed optimized single-nucleus methylome (snmC-seq3) multi-omic (snm3C-seq