A5102963446- Protein Structure and Dynamics
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Enzyme Structure and Function
- Genomics and Phylogenetic Studies
- RNA Research and Splicing
- Retinal Development and Disorders
- DNA and Nucleic Acid Chemistry
- Gene expression and cancer classification
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- Olfactory and Sensory Function Studies
- Crystallization and Solubility Studies
- Genetics and Neurodevelopmental Disorders
- Mass Spectrometry Techniques and Applications
- Electrostatics and Colloid Interactions
- Radiomics and Machine Learning in Medical Imaging
- Simulation Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Cell Image Analysis Techniques
- Computational Physics and Python Applications
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Distributed and Parallel Computing Systems
- Microbial Metabolic Engineering and Bioproduction
Jackson Laboratory
2017-2024
Florida State University
2007-2010
The SOX2 transcription factor is critical for neural stem cell (NSC) maintenance and brain development. Through chromatin immunoprecipitation (ChIP) interaction analysis (ChIA-PET), we determined genome-wide SOX2-bound regions Pol II-mediated long-range interactions in brain-derived NSCs. DNA was highly enriched distal interacting with promoters carrying epigenetic enhancer marks. Sox2 deletion caused widespread reduction of decreased gene expression. Genes showing reduced expression...
truncation variants (TTNtvs) are the most common genetic lesion identified in individuals with dilated cardiomyopathy, a disease high morbidity and mortality rates. TTNtvs reduce normal TTN (titin) protein levels, produce truncated proteins, impair sarcomere content function. Therapeutics targeting have been elusive because of immense size TTN, rarity specific TTNtvs, incomplete knowledge TTNtv pathogenicity.
The Poisson-Boltzmann (PB) equation is widely used for modeling electrostatic effects and solvation macromolecules. generalized Born (GB) model has been developed to mimic PB results at substantial lower computational cost. Here, we report an analytical GB method that reproduces with high accuracy. approach builds on previous work of Gallicchio Levy (J. Comput. Chem. 2004, 25, 479), incorporates improvement, proposed by Grycuk Phys. 2003, 119, 4817), the Coulomb-field approximation in most...
ChIA-PET (chromatin interaction analysis with paired-end tags) enables genome-wide discovery of chromatin interactions involving specific protein factors, base pair resolution. Interpretation data requires a robust analytic pipeline. Here, we introduce ChIA-PIPE, fully automated pipeline for processing, quality assessment, visualization, and analysis. ChIA-PIPE performs linker filtering, read mapping, peak calling, loop calling automates control assessment each dataset. To enable generates...
Connecting genes to their cis-regulatory elements has been enabled by genome-wide mapping of chromatin interactions using proximity ligation in ChIA-PET, Hi-C, and derivatives. However, these methods require millions input cells for high-quality data thus are unsuitable many studies when only limited available. Conversely, epigenomic profiling via transposase digestion ATAC-seq requires hundreds thousands robustly map open associated with transcription activity, but it cannot directly...
The side chains of the 20 types amino acids, owing to a large extent their different physical properties, have characteristic distributions in interior/surface regions individual proteins and interface/non-interface portions protein surfaces that bind or nucleic acids. These important structural functional implications. We developed accurate methods for predicting solvent accessibility acids from sequence interface residues structure protein-binding DNA-binding protein. are called WESA,...
Ca(2+ )binding proteins are essential for regulating the role of )in cell signaling and maintaining )homeostasis. Negatively charged residues such as Asp Glu often found in known to influence affinity protein stability. In this paper, we report a systematic investigation local charge number type coordination stability using de novo designed proteins. The approach design was chosen avoid complications cooperative binding Ca(2+)-induced conformational change associated with natural We show...
The Poisson−Boltzmann (PB) equation is widely used for modeling solvation effects. computational cost of PB has restricted its applications largely to single-conformation calculations. generalized Born (GB) model provides an approximation at substantially reduced cost. Currently the best GB methods reproduce results electrostatic energies with errors ∼5 kcal/mol. When two proteins form a complex, net contributions binding free energy are typically order 5 10 Similarly, individual residues...
Abstract The Retinoid-related orphan receptor beta (RORβ) gene encodes a developmental transcription factor and has 2 predominant isoforms created through alternative first exon usage; one specific to the retina another present more broadly in central nervous system, particularly regions involved sensory processing. RORβ belongs nuclear family plays important roles cell fate specification cortical layer formation. In mice, loss of causes disorganized layers, postnatal degeneration,...
Abstract Acquired genomic structural variants (SVs) are major hallmarks of the cancer genome. Their complexity has been challenging to reconstruct from short-read sequencing data. Here, we exploit long-read capability nanopore platform using our customized pipeline, Picky , reveal SVs diverse architecture in a breast model. From modest coverage, identified full spectrum with superior specificity and sensitivity relative analyses uncovered repetitive DNA as source variation. Examination...
Abstract ChIA-PET enables the genome-wide discovery of chromatin interactions involving specific protein factors, with base-pair resolution. Interpreting data depends on having a robust analytic pipeline. Here, we introduce ChIA-PIPE, fully automated pipeline for processing, quality assessment, analysis, and visualization. ChIA-PIPE performs linker filtering, read mapping, peak calling, loop chromatin-contact-domain can resolve allele-specific peaks loops. also automates quality-control...
Summary Extrachromosomal, circular DNA (ecDNA) is a prevalent oncogenic alteration in cancer genomes, often associated with aggressive tumor behavior and poor patient outcome. While previous studies proposed chromatin-based mobile enhancer model for ecDNA-driven oncogenesis, its precise mechanism impact remains unclear across diverse types. Our study, utilizing advanced multi-omics profiling, epigenetic editing, imaging approaches three models, reveals that ecDNA hubs are an integrated part...
Rorb encodes the Retinoic Acid Receptor-related orphan receptor beta. Mutations in either of two transcripts cause defects multiple systems, including abnormal photoreceptor abundance and morphology retina a characteristic high-stepper or duck-like gait arising from dysfunction interneurons spinal cord. is also important for cortical development cell fate specification mice. variants segregate with epilepsy comorbidities such as intellectual disability numerous clinical cases. Here we...