A5054640838- PI3K/AKT/mTOR signaling in cancer
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Protein Kinase Regulation and GTPase Signaling
- Bioinformatics and Genomic Networks
- Biochemical and Molecular Research
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Fractal and DNA sequence analysis
- Molecular Biology Techniques and Applications
- CAR-T cell therapy research
- Machine Learning in Bioinformatics
- Genomic variations and chromosomal abnormalities
- Genomics and Phylogenetic Studies
- Genetic Mapping and Diversity in Plants and Animals
- Epigenetics and DNA Methylation
- Biomedical Text Mining and Ontologies
- MicroRNA in disease regulation
- Polyamine Metabolism and Applications
- Hedgehog Signaling Pathway Studies
University of Massachusetts Amherst
2019-2024
University of Massachusetts Boston
2022
Jackson Laboratory
2013-2021
UConn Health
2014-2020
University of Connecticut
2015-2020
Yale University
2017
Stanford University
2007-2014
Howard Hughes Medical Institute
2010-2012
Peking University
2004-2005
State Key Laboratory of Turbulence and Complex Systems
2005
Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; ensemble these binding events forms regulatory network, constituting wiring diagram for cell. To examine principles human transcriptional we determined genomic information 119 transcription-related over 450 distinct experiments. We found combinatorial, co-association transcription be highly context specific: combinations at specific locations. In particular, there are significant differences...
Next-generation sequencing has greatly increased the scope and resolution of transcriptional regulation study. RNA (RNA-Seq) ChIP-Seq experiments are now generating comprehensive data on transcript abundance regulator–DNA interactions. We propose an approach for integrated analysis these based feature extraction signals, principal component analysis, regression-based selection. Compared with traditional methods, our not only offers higher power in predicting gene expression from but also...
Abstract RNA fate and function are affected by their structures interactomes. However, how RNA-binding proteins (RBPs) assemble into higher-order molecules may interact with each other to facilitate functions remain largely unknown. Here we present KARR-seq, which uses N 3 -kethoxal labeling multifunctional chemical crosslinkers covalently trap determine RNA–RNA interactions inside cells, independent of local protein binding RNA. KARR-seq depicts structure detects widespread intermolecular...
Many genes initially identified for their roles in cell fate determination or signaling during development can have a significant impact on tumorigenesis. In the developing cerebellum, Sonic hedgehog (Shh) stimulates proliferation of granule neuron precursor cells (GNPs) by activating Gli transcription factors. Inappropriate activation Shh target results unrestrained division and eventually medulloblastoma, most common pediatric brain malignancy. We find dramatic differences gene networks...
We present an integrative approach, SeqFold, that combines high-throughput RNA structure profiling data with computational prediction for genome-scale reconstruction of secondary structures. SeqFold transforms experimental information into a preference profile (SPP) and uses it to select stable candidates representing the ensemble. Under high-dimensional classification framework, efficiently matches given SPP most likely cluster structures sampled from Boltzmann-weighted is able incorporate...
Adipose tissue macrophages (ATMs) are crucial for maintaining adipose homeostasis and mediating obesity-induced metabolic abnormalities, including prediabetic conditions type 2 diabetes mellitus. Despite their key functions in regulating immunologic under normal obese conditions, a high-resolution transcriptome annotation system that can capture ATM multifaceted activation profiles has not yet been developed. This is primarily attributed to the complexity of differentiation/activation...
Abstract We have developed a strategy for estimating gene expression on Affymetrix Exon arrays. The method includes probe-specific background correction and probe selection in which subset of probes with highly correlated intensities across multiple samples are chosen to summarize expression. Our results demonstrate that the proposed model offers improvements over default arrays may provide more accurate measurements than traditional 3'
Genome-wide 3C technologies (Hi-C) are being increasingly employed to study three-dimensional (3D) genome conformations. Existing computational approaches unable integrate accumulating data facilitate studying 3D chromatin structure and function. We present HSA ( http://ouyanglab.jax.org/hsa/ ), a flexible tool that jointly analyzes multiple contact maps infer at the scale. globally searches latent underlying different cleavage footprints. Its robustness accuracy outperform or rival existing...
DNA methylation is an important epigenetic modification that undergoes dynamic changes in mammalian embryogenesis, during which both parental genomes are reprogrammed. Despite the many immunostaining studies have assessed global methylation, gene-specific patterns bovine preimplantation embryos unknown. Using reduced representation bisulfite sequencing, we determined genome-scale of sperm and individual vivo developed oocytes embryos. We show (1) major wave genome-wide demethylation was...
The oncogenic c-MYC (MYC) transcription factor has broad effects on gene expression and cell behavior. We show that MYC alters the efficiency quality of mRNA translation into functional proteins. Specifically, drives most protein components electron transport chain in lymphoma cells, many these are independent from proliferation. Specific interactions MYC-sensitive RNA-binding proteins (e.g., SRSF1/RBM42) with 5′UTR sequence motifs mediate changes. Moreover, we observe a striking shift...
Pancreatic adenocarcinoma (PDAC) epitomizes a deadly cancer driven by abnormal KRAS signaling. Here, we show that the eIF4A RNA helicase is required for translation of key signaling molecules and pharmacological inhibition has single-agent activity against murine human PDAC models at safe dose levels. EIF4A was uniquely mRNAs with long highly structured 5' untranslated regions, including those multiple G-quadruplex elements. Computational analyses identified these features in encoding...
Basal cell carcinomas (BCCs) are the most common cancers in United States. The histologic appearance distinguishes several subtypes, each of which can have a different biologic behavior. In this study, global miRNA expression was quantified by high-throughput sequencing nodular BCCs, subtype that is slow growing, and infiltrative aggressive tumors extend through dermis invade structures such as cutaneous nerves. Principal components analysis correctly classified seven eight on basis...
The signal transducer and activator of transcription 3 (STAT3) is a factor that, when dysregulated, becomes powerful oncogene found in many human cancers, including diffuse large B-cell lymphoma. Diffuse lymphoma the most common form non-Hodgkin's has two major subtypes: germinal center B-cell-like activated B-cell-like. Compared with form, lymphomas respond much more poorly to current therapies often exhibit overexpression or overactivation STAT3. To investigate how STAT3 might contribute...
Abstract Motivation: At present the computational gene identification methods in microbial genomes have a high prediction accuracy of verified translation termination site (3′ end), but much lower initiation (TIS, 5′ end). The latter is important to analysis and understanding putative protein regulatory machinery translation. Improving TIS one remaining open problems. Results: In this paper, we develop four-component statistical model describe prokaryotic genes. incorporates several features...
Single-cell RNA-sequencing (scRNAseq) technologies are rapidly evolving. Although very informative, in standard scRNAseq experiments, the spatial organization of cells tissue origin is lost. Conversely, RNA-seq designed to maintain cell localization have limited throughput and gene coverage. Mapping genes with information increases coverage while providing location. However, methods perform such mapping not yet been benchmarked. To fill this gap, we organized DREAM Single-Cell...
Recent advances in high-throughput biotechnologies have generated various types of genetic, genomic, epigenetic, transcriptomic and proteomic data across different biological conditions. It is likely that integrating from diverse experiments may lead to a more unified global view systems complex diseases. We present coherent statistical framework for distinct but related conditions through graphical models. Specifically, our designed modeling multiple networks with shared regulatory...
Zika virus (ZIKV) and dengue (DENV) are members of the Flaviviridae family RNA viruses cause severe disease in humans. ZIKV DENV share over 90% their genome sequences, however, clinical features infections very different reflecting tropism cellular effects. Here, we used simultaneous sequencing ribosome footprinting to define transcriptional translational dynamics infection human neuronal progenitor cells (hNPCs). The gene expression data showed induction aminoacyl tRNA synthetases (ARS)...