title: A novel phenotypic dissimilarity method for image-based high-throughput screens.
abstract: BACKGROUND
  Discovering functional relationships of genes through cell-based phenotyping has become an important approach in functional genomics. High-throughput imaging offers the ability to quantitatively assess complex phenotypes after perturbation by RNA interference (RNAi). Such image-based high-throughput RNAi screening studies have facilitated the discovery of novel components of gene networks and their interactions. Images generated by automated microscopy are typically analyzed by extracting quantitative features of individual cells, resulting in large multidimensional data sets. Robust and sensitive methods to interpret these data sets and to derive biologically relevant information in a high-throughput and unbiased manner remain to be developed.
  
  
  RESULTS
  Here we propose a new analysis method, PhenoDissim, which computes the phenotypic dissimilarity between cell populations via Support Vector Machine classification and cross validation. Applying this method to a kinome RNAi screening data set, we demonstrate that the proposed method shows a good replicate reproducibility, separation of controls and clustering quality, and we are able to identify siRNA phenotypes and discover potential functional links between genes.
  
  
  CONCLUSIONS
  PhenoDissim is a novel analysis method for image-based high-throughput screen, relying on two parameters which can be automatically optimized without a priori knowledge. PhenoDissim is freely available as an R package.
authors.affiliation: German Cancer Research Center (DKFZ), Div, Signaling and Functional Genomics and Department of Cell and Molecular Biology, Medical Faculty Mannheim, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany. xianzhang@gmail.com.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D016000:Cluster Analysis; D016208:Databases, Factual; D004331:Drosophila melanogaster / Q000235:genetics; D006367:HeLa Cells; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D010641:Phenotype; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015203:Reproducibility of Results; D060388:Support Vector Machine
chemical_list: D034741:RNA, Small Interfering