A5047714102- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- Acute Myeloid Leukemia Research
- Microbial Metabolic Engineering and Bioproduction
- Neural Networks and Applications
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Glioma Diagnosis and Treatment
- Developmental Biology and Gene Regulation
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- VLSI and FPGA Design Techniques
- Semiconductor materials and devices
- Genetics, Bioinformatics, and Biomedical Research
- Lung Cancer Research Studies
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Fungal and yeast genetics research
- Peptidase Inhibition and Analysis
- Advanced Data Storage Technologies
- VLSI and Analog Circuit Testing
Benaroya Research Institute
2020-2024
Fred Hutch Cancer Center
2014-2023
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2014-2019
Cancer Research Center
2017-2019
Seattle University
2004-2019
Allen Institute for Immunology
2019
Allen Institute
2019
University of Washington
2005-2018
California Institute of Technology
1998-2011
Institute for Systems Biology
2002-2008
Abstract Motivation: Molecular biotechnology now makes it possible to build elaborate systems models, but the biology community needs information standards if models are be shared, evaluated and developed cooperatively. Results: We summarize Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is software-independent language describing common research in many areas of computational biology, including cell...
Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying differences between these two tumor types, immune-related cell content potentially important contributors. In order to investigate role of IDH immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) wtIDH1 gliomas...
Different experimental technologies measure different aspects of a system and to differing depth breadth. High-throughput assays have inherently high false-positive false-negative rates. Moreover, each technology includes systematic biases nature. These differences make network reconstruction from multiple data sets difficult error-prone. Additionally, because the rapid rate progress in biotechnology, there is usually no curated exemplar set which one might estimate integration parameters....
Immune checkpoint inhibitor (ICI) treatment has recently become a first-line therapy for many non–small cell lung cancer (NSCLC) patients. Unfortunately, most NSCLC patients are refractory to ICI monotherapy, and initial attempts address this issue with secondary therapeutics have proven unsuccessful. To identify entities precluding CD8+ T accumulation in process, we performed unbiased analyses on flow cytometry, gene expression, multiplexed immunohistochemical data from patient cohort. The...
Researchers in quantitative systems biology make use of a large number different software packages for modelling, analysis, visualization, and general data manipulation. In this paper, we describe the Systems Biology Workbench (SBW), framework that allows heterogeneous application components—written diverse programming languages running on platforms—to communicate each others' capabilities via fast binary encoded-message system. Our goal was to create simple, high performance, opensource...
We describe Dizzy, a software tool for stochastically and deterministically modeling the spatially homogeneous kinetics of integrated large-scale genetic, metabolic, signaling networks. Notable features include modular simulation framework, reusable elements, complex kinetic rate laws, multi-step reaction processes, steady-state noise estimation, spatial compartmentalization.
A model was built to examine the kinetics of regulatory cascades such as occur in developmental gene networks. The relates occupancy cis-regulatory target sites transcriptional initiation rate, and thence RNA protein output. used simulate which genes encoding transcription factors are successively activated. Using realistic parameter ranges based on extensive earlier measurements sea urchin embryos, we find that transitions states sharply these simulations, with respect time or changing...
ABSTRACT The endo16 gene of Strongylocentrotus purpuratus encodes a secreted protein the embryonic and larval midgut. overall functional organization spatial temporal control system this are relatively well known from series earlier cis-regulatory studies. Our recent computational model for logic operations proximal region (Module A) specifies function interactions at each transcription factor target site Module A. Here, we extend sequence level analysis to adjacent region, B. is broadened...
To identify therapeutic targets for glioblastoma (GBM), we performed genome-wide CRISPR-Cas9 knockout (KO) screens in patient-derived GBM stem-like cells (GSCs) and human neural stem/progenitors (NSCs), non-neoplastic stem cell controls, genes required their vitro growth. Surprisingly, the vast majority GSC-lethal hits were found outside of molecular networks commonly altered GSCs (e.g., oncogenic drivers). In vivo validation GSC-specific revealed several strong hits, including wee1-like...
, encoding an acetyltransferase, is among the most frequently mutated genes in small cell lung cancer (SCLC), a deadly neuroendocrine tumor type. We report acceleration of SCLC upon
Recent updating of the World Health Organization (WHO) classification central nervous system (CNS) tumors in 2016 demonstrates first organized effort to restructure brain tumor by incorporating histomorphologic features with recurrent molecular alterations. Revised CNS diagnostic criteria also attempt reduce interobserver variability histological interpretation and provide more accurate stratification related clinical outcome. As an example, diffuse gliomas (WHO grades II–IV) are now...
The integration of data from multiple global assays is essential to understanding dynamic spatiotemporal interactions within cells. In a companion paper, we reported methodology, designated Pointillist, that can handle types technologies with different noise characteristics. Here demonstrate its application the 18 sets relating galactose utilization in yeast. These include changes mRNA and protein abundance, genome-wide protein–DNA interaction data, database information, computational...