A5066328638- Gene expression and cancer classification
- Genetics, Bioinformatics, and Biomedical Research
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Genomics and Phylogenetic Studies
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Molecular Biology Techniques and Applications
- Scientific Computing and Data Management
- Cell Image Analysis Techniques
- Protease and Inhibitor Mechanisms
- Computational Drug Discovery Methods
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Research Data Management Practices
- T-cell and B-cell Immunology
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Gene Regulatory Network Analysis
University of California, San Diego
2016-2025
Broad Institute
2011-2022
University of California San Diego Medical Center
2021-2022
La Jolla Alcohol Research
2018
Massachusetts Institute of Technology
2001-2014
University of North Carolina at Chapel Hill
2014
University of Tübingen
2004-2012
Universität Ulm
2008-2011
Harvard University Press
2008
Harvard University
2006-2008
To pursue a systematic approach to the discovery of functional connections among diseases, genetic perturbation, and drug action, we have created first installment reference collection gene-expression profiles from cultured human cells treated with bioactive small molecules, together pattern-matching software mine these data. We demonstrate that this "Connectivity Map" resource can be used find molecules sharing mechanism chemicals physiological processes, diseases drugs. These results...
The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination clinical and histopathological data. In some instances, this task is difficult or impossible because atypical presentation histopathology. To determine whether the diagnosis multiple common adult malignancies could be achieved purely molecular classification, we subjected 218 tumor samples, spanning 14 types, 90 normal tissue samples to oligonucleotide microarray gene...
It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk recurrence. Such high-risk could receive novel interventional measures. An obstacle the development of genome-based predictors outcome in with carcinoma has been lack means carry out genomewide expression profiling fixed, as opposed frozen, tissue.We aimed demonstrate feasibility gene-expression more than 6000 human genes formalin-fixed,...
Abstract Summary: RNA-seq, the application of next-generation sequencing to RNA, provides transcriptome-wide characterization cellular activity. Assessment performance and library quality is critical interpretation RNA-seq data, yet few tools exist address this issue. We introduce RNA-SeQC, a program which key measures data quality. These metrics include yield, alignment duplication rates; GC bias, rRNA content, regions (exon, intron intragenic), continuity coverage, 3′/5′ bias count...
MHC–peptide complexes mediate key functions in adaptive immunity. In a classical view, MHC-I molecules present peptides from intracellular source proteins, whereas MHC-II antigenic exogenous and membrane proteins. Nevertheless, substantial crosstalk between these two pathways has been observed. We investigated the influence of autophagy on ligandome demonstrated that peptide presentation is altered considerably upon induction autophagy. The lysosomal proteins was strongly increased contrast...
Identifying the genes responsible for human diseases requires combining information about gene position with clues biological function. The recent availability of whole-genome data sets RNA and protein expression provides powerful new sources functional insight. Here we illustrate how such can expedite disease-gene discovery, by using them to identify causing Leigh syndrome, French-Canadian type (LSFC, Online Mendelian Inheritance in Man no. 220111), a cytochrome c oxidase deficiency that...
Abstract Using a genome-scale, lentivirally delivered shRNA library, we performed massively parallel pooled screens in 216 cancer cell lines to identify genes that are required for proliferation and/or viability. Cell line dependencies on 11,000 were interrogated by 5 shRNAs per gene. The effect of each was assessed transducing population 11M cells with one shRNA-virus and determining the relative enrichment or depletion 54,000 after 16 doublings using Next Generation Sequencing. All...
Abstract Using gene expression data to classify tumor types is a very promising tool in cancer diagnosis. Previous works show several pairs of can be successfully distinguished by their patterns (Golub et al. 1999, Ben-Dor 2000, Alizadeh 2000). However, the simultaneous classification across heterogeneous set has not been well studied yet. We obtained 190 samples from 14 classes and generated combined dataset containing 16063 genes for each those samples. performed multi-class combining...
<ns4:p>Modern genomic analysis often requires workflows incorporating multiple best-of-breed tools. GenomeSpace is a web-based visual workbench that combines selection of these tools with mechanisms create data flows between them. One such tool Cytoscape 3, popular application enables and visualization graph-oriented networks. As runs on the desktop, not in web browser, integrating it into required special care creating seamless user experience enabling appropriate flows. In this paper, we...
Abstract Motivation: An important step in analyzing expression profiles from microarray data is to identify genes that can discriminate between distinct classes of samples. Many statistical approaches for assigning significance values have been developed. The Comparative Marker Selection suite consists three modules allow users apply and compare different methods computing each marker gene, a viewer assess the results, tool create derivative datasets lists based on user-defined criteria....
We introduce neutron-encoded (NeuCode) amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model Bap1, tumor suppressor and deubiquitinase whose vivo roles outside cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation cholesterol biosynthetic machinery coincident with reduced expression gluconeogenic lipid...
Abstract Summary: GeneCluster 2.0 is a software package for analyzing gene expression and other bioarray data, giving users variety of methods to build evaluate class predictors, visualize marker lists, cluster data validate results. greatly expands the analysis capabilities 1.0 by adding classification, discovery permutation test methods. It includes algorithms building testing supervised models using weighted voting k-nearest neighbor algorithms, module systematically finding evaluating...
Abstract The asparagine-specific endoprotease (AEP) controls lysosomal processing of the potential autoantigen myelin basic protein (MBP) by human B lymphoblastoid cells, a feature implicated in immunopathogenesis multiple sclerosis. In this study, we demonstrate that freshly isolated lymphocytes lack significant AEP activity and cleavage is dispensable for proteolytic MBP type cell. Instead, cathepsin (Cat) G, serine protease not endogenously synthesized lymphocytes, internalized from...
Abstract Multiple sclerosis (MS) is a detrimental disease of the central nervous system (CNS) leading to long‐term disability. In course animal models multiple (experimental autoimmune encephalomyelitis), we find enhanced activity proteasome subunits b1i, b2, b2i and b5 in CNS. We demonstrate that pharmacological inhibition by bortezomib ameliorates experimental encephalomyelitis mice rats prophylactic therapeutic treatment with reduced numbers T‐cells secreting proinflammatory cytokines....