A5069677416- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Genetics, Bioinformatics, and Biomedical Research
- Gene expression and cancer classification
- RNA modifications and cancer
- Adrenal and Paraganglionic Tumors
- Cell Image Analysis Techniques
- Biomedical Text Mining and Ontologies
- Cancer therapeutics and mechanisms
- Estrogen and related hormone effects
- Molecular Biology Techniques and Applications
- Molecular Sensors and Ion Detection
- Lung Cancer Research Studies
- Glioma Diagnosis and Treatment
- Inflammatory mediators and NSAID effects
- DNA Repair Mechanisms
- Analytical Methods in Pharmaceuticals
- MicroRNA in disease regulation
- Lung Cancer Treatments and Mutations
- Biochemical and Molecular Research
- Hormonal Regulation and Hypertension
- Click Chemistry and Applications
National Cancer Institute
2016-2025
National Institutes of Health
2013-2024
Center for Cancer Research
2015-2024
Laboratory of Molecular Genetics
2006-2023
Creative Research Enterprises (United States)
2015
Institute of Developmental Physiology
2015
Mayo Clinic
2012
SRA International (United States)
2012
Georgetown University
2007-2011
Georgetown University Medical Center
2007-2011
Abstract We have developed GoMiner, a program package that organizes lists of 'interesting' genes (for example, under- and overexpressed from microarray experiment) for biological interpretation in the context Gene Ontology. GoMiner provides quantitative statistical output files two useful visualizations. The first is tree-like structure analogous to AmiGO browser second compact, dynamically interactive 'directed acyclic graph'. Genes displayed are linked major public bioinformatics resources.
Abstract High-throughput and high-content databases are increasingly important resources in molecular medicine, systems biology, pharmacology. However, the information usually resides unwieldy databases, limiting ready data analysis integration. One resource that offers substantial potential for improvement this regard is NCI-60 cell line database compiled by U.S. National Cancer Institute, which has been extensively characterized across numerous genomic pharmacologic response platforms. In...
In an effort to develop a genomics-based approach the prediction of drug response, we have developed algorithm for classification cell line chemosensitivity based on gene expression profiles alone. Using oligonucleotide microarrays, levels 6,817 genes were measured in panel 60 human cancer lines (the NCI-60) which thousands chemical compounds been determined. We sought determine whether signatures untreated cells sufficient chemosensitivity. Gene expression-based classifiers sensitivity or...
Because most potential molecular markers and targets are proteins, proteomic profiling is expected to yield more direct answers functional pharmacological questions than does transcriptional profiling. To aid in such studies, we have developed a protocol for making reverse-phase protein lysate microarrays with larger numbers of spots previously feasible. Our first application these arrays was the 60 human cancer cell lines (NCI-60) used by National Cancer Institute screen compounds...
Expression of the vascular permeability factor/vascular endothelial growth factor (VEGPF) gene was investigated in human central nervous system (CNS) neoplasms and normal brain. Adsorption capillary activity from glioblastoma multiforme (GBM) cell conditioned medium GBM cyst fluids by anti-VEGPF antibodies demonstrated that VEGPF is secreted cells present sufficient quantities vivo to induce permeability. Cloning sequencing polymerase chain reaction-amplified brain cDNA three forms coding...
Abstract The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. NCI-60 has been characterized pharmacologically and at molecular level more extensively than any other set lines. However, no systematic mutation analysis genes causally implicated in oncogenesis reported. This study reports sequence 24 known an assessment 4 homozygous deletions. One hundred thirty-seven oncogenic mutations were...
MicroRNAs are strongly implicated in such processes as development, carcinogenesis, cell survival, and apoptosis. It is likely, therefore, that they can also modulate sensitivity resistance to anticancer drugs substantial ways. To test this hypothesis, we studied the pharmacologic roles of three microRNAs previously cancer biology (let-7i, mir-16, mir-21) used silico methods microRNA effects more broadly. In experimental system, increased expression individual by transfecting their...
Advances in the high-throughput omic technologies have made it possible to profile cells a large number of ways at DNA, RNA, protein, chromosomal, functional, and pharmacological levels. A persistent problem is that some classes molecular data are labeled with gene identifiers, others transcript or protein still chromosomal locations. What has lagged behind ability integrate resulting uncover complex relationships patterns. Those issues reflected full form by on panel 60 diverse human cancer...
Abstract To evaluate the utility of transcript profiling for prediction protein expression levels, we compared profiles across NCI-60 cancer cell panel, which represents nine tissues origin. For that analysis, present here two new profile data sets (A based on Affymetrix HG-U95 and HG-U133A chips; Affymetrix, Santa Clara, CA) one set (based reverse-phase lysate arrays). The are available online at http://discover.nci.nih.gov in CellMiner program package. Using combination with our previously...
DNA-damaging agents (DDAs) constitute the backbone of treatment for most human tumors. Here we used National Cancer Institute Antitumor Cell Line Panel (the NCI-60) to identify predictors cancer cell response topoisomerase I (Top1) inhibitors, a widely class DDAs. We assessed NCI-60 transcriptome using Affymetrix Human Exon 1.0 ST microarrays and correlated in vitro activity four Top1 inhibitors with gene expression 60 lines. A single gene, Schlafen-11 (SLFN11), showed an extremely...
Abstract The NCI-60 cell lines are the most frequently studied human tumor in cancer research. This panel has generated extensive pharmacology database worldwide. In addition, these have been intensely investigated, providing a unique platform for hypothesis-driven research focused on enhancing our understanding of biology. Here, we report comprehensive analysis coding variants identified by whole exome sequencing, list possible specific community. Furthermore, identify pharmacogenomic...
Abstract CellMiner Cross-Database (CellMinerCDB, discover.nci.nih.gov/cellminercdb) allows integration and analysis of molecular pharmacological data within across cancer cell line datasets from the National Cancer Institute (NCI), Broad Institute, Sanger/MGH MD Anderson Center (MDACC). We present CellMinerCDB 1.2 with updates to NCI-60, Cell Line Encyclopedia Sanger/MGH, addition new datasets, including NCI-ALMANAC drug combination, MDACC Project proteomic, NCI-SCLC DNA copy number...
Abstract Membrane transporters and channels (collectively the transportome) govern cellular influx efflux of ions, nutrients, drugs. We used oligonucleotide arrays to analyze gene expression transportome in 60 human cancer cell lines by National Cancer Institute for drug screening. Correlating with potencies 119 standard anticancer drugs identified known drug-transporter interactions suggested novel ones. Folate, nucleoside, amino acid positively correlated chemosensitivity their respective...
Abstract Advances in the understanding of cancer cell biology and response to drug treatment have benefited from new molecular technologies methods for integrating information multiple sources. The NCI-60, a panel 60 diverse human lines, has been used by National Cancer Institute screen >100,000 chemical compounds natural product extracts anticancer activity. NCI-60 also profiled mRNA protein expression, mutational status, chromosomal aberrations, DNA copy number, generating an...
Abstract Chromosome rearrangement, a hallmark of cancer, has profound effects on carcinogenesis and tumor phenotype. We used panel 60 human cancer cell lines (the NCI-60) as model system to identify relationships among DNA copy number, mRNA expression level, drug sensitivity. For each 64 cancer-relevant genes, we calculated all 4,096 possible Pearson's correlation coefficients relating number (assessed by comparative genomic hybridization using bacterial artificial chromosome microarrays)...
Abstract The National Cancer Institute's NCI-60 cell line panel, the most extensively characterized set of cells in existence and a public resource, is frequently used as screening tool for drug discovery. Because many laboratories around world rely on data from cells, confirmation their genetic identities represents an essential step validating results them. Given consequences contamination or misidentification, quality control measures should routinely include DNA fingerprinting. We have,...
VARICELLA is a common exanthematous disease that affects most persons during childhood. Zoster prevalent in the elderly and characterized by vesicular lesions similar to those of varicella but typically confined single cutaneous dermatome.1 A series careful clinical epidemiologic studies conducted over past century have led recognition zoster are closely related infections.2 3 4 Those observations determination viruses behave similarly on vitro cultivation Hope-Simpson postulate represents...
Abstract Topoisomerase I (Top1) is a proven target for cancer therapeutics, and the level of Top1 in tumors has been used as biomarker chemotherapeutic efficacy. In this study, we report development validation two-site enzyme chemiluminescent immunoassay Top1, which to measure levels NCI-60 cell line panel. ranged from 0.9 9.8 ng/mL/μg protein extract these lines. Levels varied both within between types but were generally highest colon leukemia lines lowest central nervous system renal mRNA...
CellMinerCDB provides a web-based resource (https://discover.nci.nih.gov/cellminercdb/) for integrating multiple forms of pharmacological and genomic analyses, unifying the richest cancer cell line datasets (the NCI-60, NCI-SCLC, Sanger/MGH GDSC, Broad CCLE/CTRP). enables data queries genomics gene regulatory network exploration pharmacogenomic determinants drug signatures. It leverages overlaps lines drugs across databases to examine reproducibility expand pathway analyses. We illustrate...
Platinum-derived drugs such as cisplatin and carboplatin are among the most commonly used cancer chemotherapy drugs, but very few specific molecular cellular markers predicting differential sensitivity to these agents in a given tumor type have been clearly identified. Epigenetic gene silencing is increasingly being recognized factor conferring distinct tumoral drug sensitivity, so we comprehensive DNA methylation microarray platform interrogate widely characterized NCI60 panel of human cell...
Abstract As part of the Spotlight on Molecular Profiling series, we present here new profiling studies mRNA and microRNA expression for 60 cell lines National Cancer Institute (NCI) Developmental Therapeutics program (DTP) drug screen (NCI-60) using 41,000-probe Agilent Whole Human Genome Oligo Microarray 15,000-feature V2. The levels ∼21,000 genes 723 human microRNAs were measured. These include quadruplicate technical replicates six eight microRNA, respectively, duplicates remaining lines....
CellMiner-SCLC (https://discover.nci.nih.gov/SclcCellMinerCDB/) integrates drug sensitivity and genomic data, including high-resolution methylome transcriptome from 118 patient-derived small cell lung cancer (SCLC) lines, providing a resource for research into this "recalcitrant cancer." We demonstrate the reproducibility stability of data multiple sources validate SCLC consensus nomenclature on basis expression master transcription factors NEUROD1, ASCL1, POU2F3, YAP1. Our analyses reveal...