title: ASSIGN: context-specific genomic profiling of multiple heterogeneous biological pathways.
abstract: BACKGROUND
  Although gene-expression signature-based biomarkers are often developed for clinical diagnosis, many promising signatures fail to replicate during validation. One major challenge is that biological samples used to generate and validate the signature are often from heterogeneous biological contexts-controlled or in vitro samples may be used to generate the signature, but patient samples may be used for validation. In addition, systematic technical biases from multiple genome-profiling platforms often mask true biological variation. Addressing such challenges will enable us to better elucidate disease mechanisms and provide improved guidance for personalized therapeutics.
  
  
  RESULTS
  Here, we present a pathway profiling toolkit, Adaptive Signature Selection and InteGratioN (ASSIGN), which enables robust and context-specific pathway analyses by efficiently capturing pathway activity in heterogeneous sets of samples and across profiling technologies. The ASSIGN framework is based on a flexible Bayesian factor analysis approach that allows for simultaneous profiling of multiple correlated pathways and for the adaptation of pathway signatures into specific disease. We demonstrate the robustness and versatility of ASSIGN in estimating pathway activity in simulated data, cell lines perturbed pathways and in primary tissues samples including The Cancer Genome Atlas breast carcinoma samples and liver samples exposed to genotoxic carcinogens.
  
  
  METHODS
  Software for our approach is available for download at: http://www.bioconductor.org/packages/release/bioc/html/ASSIGN.html and https://github.com/wevanjohnson/ASSIGN.
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA.
authors.forename: Mumtahena
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Piccolo
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gusenleitner
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA.
authors.forename: Nader N
authors.initials: NN
authors.lastname: El-Chaar
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Monti
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA.
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Bild
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118 USA, Department of Biomedical Informatics and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 USA.
authors.forename: W Evan
authors.initials: WE
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D023281:Genomics / Q000379:methods; D006801:Humans; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D012984:Software