title: EXPANDS: expanding ploidy and allele frequency on nested subpopulations.
abstract: BACKGROUND
  Several cancer types consist of multiple genetically and phenotypically distinct subpopulations. The underlying mechanism for this intra-tumoral heterogeneity can be explained by the clonal evolution model, whereby growth advantageous mutations cause the expansion of cancer cell subclones. The recurrent phenotype of many cancers may be a consequence of these coexisting subpopulations responding unequally to therapies. Methods to computationally infer tumor evolution and subpopulation diversity are emerging and they hold the promise to improve the understanding of genetic and molecular determinants of recurrence.
  
  
  RESULTS
  To address cellular subpopulation dynamics within human tumors, we developed a bioinformatic method, EXPANDS. It estimates the proportion of cells harboring specific mutations in a tumor. By modeling cellular frequencies as probability distributions, EXPANDS predicts mutations that accumulate in a cell before its clonal expansion. We assessed the performance of EXPANDS on one whole genome sequenced breast cancer and performed SP analyses on 118 glioblastoma multiforme samples obtained from TCGA. Our results inform about the extent of subclonal diversity in primary glioblastoma, subpopulation dynamics during recurrence and provide a set of candidate genes mutated in the most well-adapted subpopulations. In summary, EXPANDS predicts tumor purity and subclonal composition from sequencing data.
  
  
  METHODS
  EXPANDS is available for download at http://code.google.com/p/expands (matlab version--used in this manuscript) and http://cran.r-project.org/web/packages/expands (R version).
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94143, USA, Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany, Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94158, USA, Department of Neurology, University of California San Francisco, San Francisco, CA 94143, USA, Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA, Chair of Genome Oriented Bioinformatics, Center of Life and Food Science, Freising-Weihenstephan, Technische Universität München, 80333, Munich, Germany, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94158 and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Noemi
authors.initials: N
authors.lastname: Andor
authors.forename: Julie V
authors.initials: JV
authors.lastname: Harness
authors.forename: Sabine
authors.initials: S
authors.lastname: Müller
authors.forename: Hans W
authors.initials: HW
authors.lastname: Mewes
authors.forename: Claudia
authors.initials: C
authors.lastname: Petritsch
mesh_terms: D005787:Gene Frequency; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D011003:Ploidies; D011336:Probability; D012008:Recurrence