A5041882348- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- PARP inhibition in cancer therapy
- Gene Regulatory Network Analysis
- RNA Research and Splicing
- Complex Network Analysis Techniques
- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Genomics and Phylogenetic Studies
- Immune cells in cancer
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Microbial Metabolic Engineering and Bioproduction
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Immunotherapy and Immune Responses
- Genomic variations and chromosomal abnormalities
- CAR-T cell therapy research
- Cancer therapeutics and mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Evolution and Genetic Dynamics
- Expert finding and Q&A systems
St. Jude Children's Research Hospital
2017-2025
Yale University
2011-2022
University of Washington
2016
Whitney Museum of American Art
2010-2015
Institute of Molecular Biology and Biophysics
2010
Stony Brook University
2005-2006
Brookhaven National Laboratory
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...
Uniform processing and detailed annotation of human, worm fly RNA-sequencing data reveal ancient, conserved features the transcriptome, shared co-expression modules (many enriched in developmental genes), matched expression patterns across development similar extent non-canonical, non-coding transcription; furthermore, are used to create a single, universal model predict gene-expression levels for all three organisms from chromatin at promoter. In this paper modENCODE consortium reports on...
Abstract The model organism Encylopedia of Regulatory Elements (modERN) project was designed to generate genome-wide binding profiles for the majority transcription... To develop a catalog regulatory sites in two major organisms, Drosophila melanogaster and Caenorhabditis elegans, modERN (model Encyclopedia Networks) consortium has systematically assayed transcription factors (TFs). Combined with data produced by our predecessor, modENCODE (Model Organism ENCyclopedia Of DNA Elements), we...
Hi-C is currently the most widely used assay to investigate 3D organization of genome and study its role in gene regulation, DNA replication, disease. However, experiments are costly perform involve multiple complex experimental steps; thus, accurate methods for measuring quality reproducibility data essential determine whether output should be further a study. Using real simulated data, we profile performance several recently proposed assessing population including HiCRep, GenomeDISCO,...
Statistical models have been used to quantify the relationship between gene expression and transcription factor (TF) binding signals. Here we apply large-scale data generated by ENCODE project study transcriptional regulation TFs. Our results reveal a notable difference in prediction accuracy of levels start sites (TSSs) captured different technologies RNA extraction protocols. In general, TSSs with high CpG content are more predictable than those low content. For genes alternative TSSs,...
We develop a statistical framework to study the relationship between chromatin features and gene expression. This can be used predict expression of protein coding genes, as well microRNAs. demonstrate prediction in variety contexts, focusing particularly on modENCODE worm datasets. Moreover, our reveals positional contribution around genes (upstream or downstream) distinct overall levels.
Genome-wide proximity ligation based assays like Hi-C have opened a window to the 3D organization of genome. In so doing, they present data structures that are different from conventional 1D signal tracks. To exploit 2D nature contact maps, matrix techniques spectral analysis particularly useful. Here, we HiC-spector, collection matrix-related functions for analyzing maps. particular, introduce novel reproducibility metric quantifying similarity between maps on decomposition. The...
Abstract Spatial transcriptomics (ST) has advanced our understanding of tissue regionalization by enabling the visualization gene expression within whole-tissue sections, but current approaches remain plagued challenge achieving single-cell resolution without sacrificing whole-genome coverage. Here we present Spotiphy (spot imager with pseudo-single-cell-resolution histology), a computational toolkit that transforms sequencing-based ST data into single-cell-resolved whole-transcriptome...
We have accumulated a large amount of biological network data and expect even more to come. Soon, we anticipate being able compare many different networks as commonly do for molecular sequences. It has long been believed that these change, or "rewire", at rates. is therefore important develop framework quantify the differences between in unified fashion. developed such formalism based on analogy simple models sequence evolution, used it conduct systematic study rewiring all currently...
We performed computational reconstruction of the in silico gene regulatory networks DREAM3 Challenges. Our task was to learn from two types data, namely expression profiles deletion strains (the 'deletion data') and time series trajectories after some initial perturbation 'perturbation data'). In course developing prediction method, we observed that data contained different complementary information about underlying network. particular, allow for detection direct activities with strong...
We present a network framework for analyzing multi-level regulation in higher eukaryotes based on systematic integration of various high-throughput datasets. The network, namely the integrated regulatory consists three major types regulation: TF→gene, TF→miRNA and miRNA→gene. identified target genes miRNAs set TFs ChIP-Seq binding profiles, predicted targets using annotated 3′UTR sequences conservation information. Making use system-wide RNA-Seq we classified transcription factors into...
The genome has often been called the operating system (OS) for a living organism. A computer OS is described by regulatory control network termed call graph, which analogous to transcriptional in cell. To apply our firsthand knowledge of architecture software systems understand cellular design principles, we present comparison between well-studied bacterium ( Escherichia coli ) and graph canonical (Linux) terms topology evolution. We show that both networks have fundamentally hierarchical...
Gene regulatory networks have been shown to share some common aspects with commonplace social governance structures. Thus, we can get intuition into their organization by arranging them well-known hierarchical layouts. These hierarchies, in turn, be placed between the extremes of autocracies, well-defined levels and clear chains command, democracies, without such defined more co-regulatory partnerships regulators. In general, presence decreases variation information flow amongst nodes within...
The presence of web-based communities is a distinctive signature Web 2.0. feature means that information propagation within each community highly facilitated, promoting complex collective dynamics in view exchange. In this work, we focus on scientists and study, particular, how the awareness scientific paper spread. Our work based web usage statistics obtained from PLoS Article Level Metrics dataset compiled by PLoS. cumulative number HTML views was found to follow long tail distribution...
Many signaling and other genes known as "hidden" drivers may not be genetically or epigenetically altered differentially expressed at the mRNA protein levels, but, rather, drive a phenotype such tumorigenesis via post-translational modification mechanisms. However, conventional approaches based on genomics differential expression are limited in exposing hidden drivers. Here, we present comprehensive algorithm toolkit NetBID2 (data-driven network-based Bayesian inference of drivers, version...
Abstract Increasingly, high-dimensional genomics data are becoming available for many organisms.Here, we develop OrthoClust simultaneously clustering across multiple species. is a computational framework that integrates the co-association networks of individual species by utilizing orthology relationships genes between It outputs optimized modules fundamentally cross-species, which can either be conserved or species-specific. We demonstrate application using RNA-Seq expression profiles...
Genome-wide proximity ligation based assays such as Hi-C have revealed that eukaryotic genomes are organized into structural units called topologically associating domains (TADs). From a visual examination of the chromosomal contact map, however, it is clear organization not simple or obvious. Instead, TADs exhibit various length scales and, in many cases, nested arrangement. Here, by exploiting resemblance between map and densely connected modules network, we formulate TAD identification...
Many biological networks naturally form a hierarchy with preponderance of downward information flow. In this study, we define score to quantify the degree in network and develop simulated-annealing algorithm maximize hierarchical globally over network. We apply our determine structure phosphorylome detail investigate correlation between its kinase properties. also compare it regulatory network, finding that is more than regulome.
The topology of the gene-regulatory network has been extensively analyzed. Now, given large amount available functional genomic data, it is possible to go beyond this and systematically study regulatory circuits in terms logic elements. To end, we present Loregic, a computational method integrating gene expression characterize cooperativity factors. Loregic uses all 16 two-input-one-output gates (e.g. AND or XOR) describe triplets two factors regulating common target. We attempt find gate...
Worldwide, more than 250 people become infected with HIV every hour [1], yet an individual's chance of becoming after a single sexual exposure, the predominant mode transmission, is often lower one in 100 [2]. When sexually transmitted HIV-1 infection does occur, it usually initiated by virus, called founder strain, despite presence thousands genetically diverse viral strains transmitting partner [3]. Here we review evidence from molecular biology and virology suggesting that heterogeneity...
Pediatric sarcomas represent a heterogeneous group of malignancies that exhibit variable response to DNA-damaging chemotherapy. Schlafen family member 11 protein (SLFN11) increases sensitivity replicative stress and has been implicated as potential biomarker predict agents (DDA). SLFN11 expression was quantified in 220 children with solid tumors using IHC. Sensitivity the PARP inhibitor talazoparib (TAL) topoisomerase I irinotecan (IRN) assessed sarcoma cell lines, including knock-out (KO)...