A5046119730- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Genomics and Phylogenetic Studies
- Peroxisome Proliferator-Activated Receptors
- T-cell and B-cell Immunology
- Gene Regulatory Network Analysis
- Immunotherapy and Immune Responses
- Adipose Tissue and Metabolism
- Chromosomal and Genetic Variations
- Glycosylation and Glycoproteins Research
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Galectins and Cancer Biology
- Genetics, Bioinformatics, and Biomedical Research
- Molecular Biology Techniques and Applications
- Genetic Associations and Epidemiology
- Heme Oxygenase-1 and Carbon Monoxide
- Epigenetics and DNA Methylation
- Sphingolipid Metabolism and Signaling
- Hedgehog Signaling Pathway Studies
- Machine Learning in Bioinformatics
University of Pennsylvania
2021-2024
Ulsan National Institute of Science and Technology
2014-2023
Cancer Research Institute
2023
California University of Pennsylvania
2022
Korea University of Science and Technology
2019
Abstract The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, mitochondria, respectively; all play important roles tumorigenesis by regulating protein homeostasis response to stress. Thus, simultaneous inhibition of paralogs is a reasonable strategy for cancer therapy. However, since existing pan-Hsp90 inhibitor does not accumulate potential anticancer activity has yet been fully examined vivo. Analysis Cancer Genome Atlas database...
Abstract Meta-analyses increase statistical power by combining statistics from multiple studies. Meta-analysis methods have mostly been evaluated under the condition that all data in each study an association with given phenotype. However, specific experimental conditions or genetic heterogeneity can result “unassociated statistics” are derived null distribution. Here, we show of conventional meta-analysis rapidly decreases as increasing number unassociated included, whereas classical...
Abstract Architectural stripes tend to form at genomic regions harboring genes with salient roles in cell identity and function. Therefore, the accurate identification quantification of these features are essential for understanding lineage-specific gene regulation. Here, we present Stripenn, an algorithm rooted computer vision systematically detect quantitate architectural from chromatin conformation measurements using various technologies. We demonstrate that Stripenn outperforms existing...
Abstract Integration of single-cell RNA sequencing data between different samples has been a major challenge for analyzing cell populations. However, strategies to integrate differential expression analysis remain underinvestigated. Here, we benchmark 46 workflows with multiple batches. We show that batch effects, depth and sparsity substantially impact their performances. Notably, find the use batch-corrected rarely improves sparse data, whereas covariate modeling substantial effects. low...
Pathway-based analysis in genome-wide association study (GWAS) is being widely used to uncover novel multi-genic functional associations. Many of these pathway-based methods have been test the enrichment associated genes pathways, but exhibited low powers and were highly affected by free parameters. We present method software GSA-SNP2 for pathway GWAS P-value data. provides high power, decent type I error control fast computation incorporating random set model SNP-count adjusted gene score....
Benchmarking RNA-seq differential expression analysis methods using spike-in and simulated data has often yielded inconsistent results. The data, which were generated from the same bulk RNA sample, only represent technical variability, making test results less reliable. We compared performance of 12 for including recent variants in widely used software packages, both simulation negative binomial (NB) model. Performance edgeR, DESeq2, ROTS was particularly different between two benchmark...
Dysregulation of extracellular matrix proteins in obese adipose tissue (AT) induces systemic insulin resistance. The metabolic roles type VI collagen and its cleavage peptide endotrophin AT are well established. However, the mechanisms regulating generation remain elusive. Herein, we identified that several endotrophin-containing peptides (pre-endotrophins) were generated from COL6A3 chain a stepwise manner for efficient production mature endotrophin, partly through action hypoxia-induced...
Abstract O-GlcNAcylated proteins are abundant in the brain and associated with neuronal functions neurodegenerative diseases. Although several studies have reported effects of aberrant regulation O-GlcNAcylation on function, roles synaptic function remain unclear. To understand effect brain, we used Oga +/− mice which an increased level O-GlcNAcylation, found that exhibited impaired spatial learning memory. Consistent this result, showed a defect hippocampal plasticity. heterozygosity causes...
Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor that regulates adipocyte differentiation and glucose homeostasis. The transcriptional activity of PPARγ regulated not only by ligands but also post-translational modifications (PTMs). In this study, we demonstrate novel E3 ligase PPARγ, tripartite motif-containing 25 (TRIM25), directly induced the ubiquitination leading to its proteasome-dependent degradation. During differentiation, both...
Abstract Emerging evidence suggests that aberrant O-GlcNAcylation is associated with tumorigenesis. Many oncogenic factors are O-GlcNAcylated, which modulates their functions. However, it remains unclear how and O-GlcNAc cycling enzymes, transferase (OGT) O-GlcNAcase (OGA), affect the development of cancer in animal models. In this study, we show reduced level OGA attenuates colorectal tumorigenesis induced by Adenomatous polyposis coli ( Apc ) mutation. The levels enzymes were...
Deregulated pathways identified from transcriptome data of two sample groups have played a key role in many genomic studies. Gene-set enrichment analysis (GSEA) has been commonly used for pathway or functional microarray data, and it is also being applied to RNA-seq data. However, most so far only small replicates. This enforces apply the gene-permuting GSEA method (or preranked GSEA) which results great number false positives due inter-gene correlation each gene-set. We demonstrate that...
In differential expression analysis of RNA-sequencing (RNA-seq) read count data for two sample groups, it is known that highly expressed genes (or longer genes) are more likely to be differentially which called bias gene length bias). This had great effect on the downstream Gene Ontology over-representation analysis. However, such a has not been systematically analyzed different replicate types RNA-seq data. We show dispersion coefficient in negative binomial modeling counts critical...
Abstract Dysregulation of the adipo‐osteogenic differentiation balance mesenchymal stem cells (MSCs), which are common progenitor adipocytes and osteoblasts, has been associated with many pathophysiologic diseases, such as obesity, osteopenia, osteoporosis. Growing evidence suggests that lipid metabolism is crucial for maintaining cell homeostasis differentiation; however, detailed underlying mechanisms largely unknown. Here, we demonstrate glucosylceramide (GlcCer) its synthase, synthase...
We present a novel approach to identify human microRNA (miRNA) regulatory modules (mRNA targets and relevant cell conditions) by biclustering large collection of mRNA fold-change data for sequence-specific targets. Bicluster were assessed using validated messenger RNA (mRNA) exhibited on an average 17.0% (median 19.4%) improved gain in certainty (sensitivity + specificity). The net was further increased up 32.0% 33.4%) incorporating functional networks analyzed cancer-specific biclusters...
Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipose tissue biology. In obesity, phosphorylation PPARγ at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated (ERK) orchestrates diabetic gene reprogramming via dysregulation specific expression. Although many recent studies have focused on the development non-classical agonist drugs that inhibit Ser273, molecular mechanism dephosphorylation not well characterized. Here, we report...
Gene-set analysis (GSA) has been commonly used to identify significantly altered pathways or functions from omics data. However, GSA often yields a long list of gene-sets, necessitating efficient post-processing for improved interpretation. Existing methods cluster the gene-sets based on extent their overlap summarize results without considering interactions between gene-sets.Here, we presented novel network-weighted gene-set clustering that incorporates both and protein-protein interaction...
Abstract Summary We present an R-Shiny package, netGO, for novel network-integrated pathway enrichment analysis. The conventional Fisher’s exact test (FET) considers the extent of overlap between target genes and gene-sets, while recent network-based analysis tools consider only network interactions two. netGO implements intuitive framework to integrate both networks into a single score, adaptively resamples based on degrees assess enrichment. In benchmark tests gene expression genome-wide...