A5045820772- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Advanced Electron Microscopy Techniques and Applications
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Protein Structure and Dynamics
- Cancer Genomics and Diagnostics
- Computational Physics and Python Applications
- RNA modifications and cancer
- Nuclear Structure and Function
- Single-cell and spatial transcriptomics
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- Genetic Mapping and Diversity in Plants and Animals
- Electron and X-Ray Spectroscopy Techniques
- Cell Image Analysis Techniques
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Gene expression and cancer classification
- Computational Drug Discovery Methods
- Photosynthetic Processes and Mechanisms
- Mass Spectrometry Techniques and Applications
- Genomic variations and chromosomal abnormalities
- Herpesvirus Infections and Treatments
University of Southern California
2014-2025
QB3
2004-2025
University of California, Los Angeles
2019-2025
Quantitative BioSciences
2023
UCLA Health
2022
APLA Health
2020
European Molecular Biology Laboratory
2011
Academy of Mathematics and Systems Science
2010
Institute of Structural and Molecular Biology
2010
Birkbeck, University of London
2010
Numerous features distinguish prokaryotes from eukaryotes, chief among which are the distinctive internal membrane systems of eukaryotic cells. These form elaborate compartments and vesicular trafficking pathways, sequester chromatin within nuclear envelope. The pore complex is portal that specifically mediates macromolecular across Although it generally understood these evolved specialized invaginations prokaryotic plasma membrane, not clear how could have organisms with no analogous...
Genome-wide proximity ligation assays allow the identification of chromatin contacts at unprecedented resolution. Several studies reveal that mammalian chromosomes are composed topological domains (TDs) in sub-mega base resolution, which appear to be conserved across cell types and some extent even between organisms. Identifying is now an important step toward understanding structure functions spatial genome organization. However, current methods for TD demand extensive computational...
We propose a probabilistic method, CancerLocator, which exploits the diagnostic potential of cell-free DNA by determining not only presence but also location tumors. CancerLocator simultaneously infers proportions and tissue-of-origin tumor-derived in blood sample using genome-wide methylation data. outperforms two established multi-class classification methods on simulations real data, even with low proportion scenarios. achieves promising results patient plasma samples sequencing coverage.
In this paper we show that tethering of heterochromatic regions to nuclear landmarks and random encounters chromosomes in the confined volume are sufficient explain higher-order organization budding yeast genome. We have quantitatively characterized contact patterns territories emerge when allowed behave as constrained but otherwise randomly configured flexible polymer chains nucleus. Remarkably, encounter model explains a statistical manner experimental hallmarks S. cerevisiae genome...
Significance We provide a method for population-based structure modeling of whole diploid genomes using Hi-C data. The considers the stochastic nature chromosome structures, which allows detailed analysis dynamic landscape genome organizations. predict and experimentally validate presence chromosome-specific higher-order centromere clusters, can play key role in spatial organization human genome, specifically influencing overall positioning, as well preference specific conformations. Our...
The detection of tumor-derived cell-free DNA in plasma is one the most promising directions cancer diagnosis. major challenge such an approach how to identify tiny amount tumor DNAs out total blood. Here we propose ultrasensitive method, termed 'CancerDetector', using methylation profiles DNAs. key our method probabilistically model joint states multiple adjacent CpG sites on individual sequencing read, order exploit pervasive nature for signal amplification. Therefore, CancerDetector can...
The nuclear pore complex (NPC) consists of multiple copies approximately 30 different proteins [nucleoporins (nups)], forming a channel in the envelope that mediates macromolecular transport between cytosol and nucleus. With <5% nup residues currently available experimentally determined structures, little is known about detailed structure NPC. Here, we use combined computational biochemical approach to assign folds for 95% yeast vertebrate nups. These fold assignments suggest an underlying...
Abstract Background Genome structures are dynamic and non-randomly organized in the nucleus of higher eukaryotes. To maximize accuracy coverage three-dimensional genome structural models, it is important to integrate all available sources experimental information about a genome’s organization. It remains major challenge such data from various complementary methods. Here, we present an approach for integration determine population complete that statistically consistent with both genome-wide...
Abstract Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor DNA, molecular heterogeneity cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a approach address these challenges. It consists an assay, cfMethyl-Seq, for cost-effective sequencing the methylome (with > 12-fold enrichment over whole genome bisulfite in CpG islands), computational method extract methylation information diagnose patients....
Abstract A multitude of sequencing-based and microscopy technologies provide the means to unravel relationship between three-dimensional organization genomes key regulatory processes genome function. Here, we develop a multimodal data integration approach produce populations single-cell structures that are highly predictive for nuclear locations genes bodies, local chromatin compaction spatial segregation functionally related chromatin. We demonstrate can compensate systematic errors in some...
Abstract Summary: Genome-wide proximity ligation assays, e.g. Hi-C and its variant TCC, have recently become important tools to study spatial genome organization. Removing biases from chromatin contact matrices generated by such techniques is a critical preprocessing step of subsequent analyses. The continuing decline sequencing costs has led an ever-improving resolution the data, resulting in very large contacts. Such large-size matrices, however, pose great challenge on memory usage speed...
Neutrophils are responsible for the first line of defense against invading pathogens. Their nuclei uniquely structured as multiple lobes that establish a highly constrained nuclear environment. Here we found neutrophil differentiation was not associated with large-scale changes in number and sizes topologically associating domains (TADs). However, genomes were enriched long-range genomic interactions spanned TADs. Population-based simulation spherical toroid revealed declining radii gyration...
Abstract The dynamic three-dimensional (3D) organization of the human genome (the “4D Nucleome”) is closely linked to function. Here, we integrate a wide variety genomic data generated by 4D Nucleome Project provide detailed view 3D in widely used embryonic stem cells (H1-hESCs) and immortalized fibroblasts (HFFc6). We extensive benchmarking mapping assays these diverse datasets annotate spatial features across scales. reveal rich complexity chromatin domains their sub-nuclear positions,...
Subcellular maps of β cells reveal the coordinated reorganization organelles during insulin secretion.