title: UNDO: a Bioconductor R package for unsupervised deconvolution of mixed gene expressions in tumor samples.
abstract: CONCLUSIONS
  We develop a novel unsupervised deconvolution method, within a well-grounded mathematical framework, to dissect mixed gene expressions in heterogeneous tumor samples. We implement an R package, UNsupervised DecOnvolution (UNDO), that can be used to automatically detect cell-specific marker genes (MGs) located on the scatter radii of mixed gene expressions, estimate cellular proportions in each sample and deconvolute mixed expressions into cell-specific expression profiles. We demonstrate the performance of UNDO over a wide range of tumor-stroma mixing proportions, validate UNDO on various biologically mixed benchmark gene expression datasets and further estimate tumor purity in TCGA/CPTAC datasets. The highly accurate deconvolution results obtained suggest not only the existence of cell-specific MGs but also UNDO's ability to detect them blindly and correctly. Although the principal application here involves microarray gene expressions, our methodology can be readily applied to other types of quantitative molecular profiling data.
  
  
  METHODS
  UNDO is available at http://bioconductor.org/packages.
authors.affiliation: Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231 and Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Niya
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231 and Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Gong
authors.affiliation: Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231 and Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Clarke
authors.affiliation: Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231 and Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Lulu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231 and Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
authors.affiliation: Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231 and Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231 and Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.affiliation: Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231 and Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xuan
authors.affiliation: Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231 and Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D001943:Breast Neoplasms / Q000235:genetics*; D003198:Computer Simulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017423:Sequence Analysis, RNA / Q000379:methods*; D012984:Software; D014407:Tumor Cells, Cultured