title: CloneCNA: detecting subclonal somatic copy number alterations in heterogeneous tumor samples from whole-exome sequencing data.
abstract: BACKGROUND
  Copy number alteration is a main genetic structural variation that plays an important role in tumor initialization and progression. Accurate detection of copy number alterations is necessary for discovering cancer-causing genes. Whole-exome sequencing has become a widely used technology in the last decade for detecting various types of genomic aberrations in cancer genomes. However, there are several major issues encountered in these detection problems, including normal cell contamination, tumor aneuploidy, and intra-tumor heterogeneity. Especially, deciphering the intra-tumor heterogeneity is imperative for identifying clonal and subclonal copy number alterations.
  
  
  RESULTS
  We introduce CloneCNA, a novel bioinformatics tool for efficiently addressing these issues and automatically detecting clonal and subclonal somatic copy number alterations from heterogeneous tumor samples. CloneCNA fully explores the log ratio of read counts between paired tumor-normal samples and tumor B allele frequency of germline heterozygous SNP positions, further employs efficient statistical models to quantitatively represent copy number status of tumor sample containing multiple clones. We examine CloneCNA on simulated heterogeneous and real tumor samples, and the results demonstrate that CloneCNA has higher power to detect copy number alterations than existing methods.
  
  
  CONCLUSIONS
  CloneCNA, a novel algorithm is developed to efficiently and accurately identify somatic copy number alterations from heterogeneous tumor samples. We demonstrate the statistical framework of CloneCNA represents a remarkable advance for tumor whole-exome sequencing data. We expect that CloneCNA will promote cancer-focused studies for investigating the role of clonal evolution and elucidating critical events benefiting tumor tumourigenesis and progression.
authors.affiliation: School of Information Science and Technology, University of Science and Technology of China, Hefei, AH230027, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yu
authors.affiliation: School of Information Science and Technology, University of Science and Technology of China, Hefei, AH230027, China. aoli@ustc.edu.cn.|Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, AH230027, China. aoli@ustc.edu.cn.
authors.forename: Ao
authors.initials: A
authors.lastname: Li
authors.affiliation: School of Information Science and Technology, University of Science and Technology of China, Hefei, AH230027, China.|Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, AH230027, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D000782:Aneuploidy; D056915:DNA Copy Number Variations; D059472:Exome / Q000235:genetics*; D005787:Gene Frequency; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
keywords: Copy number alteration; Hidden Markov model; Intra-tumor heterogeneity; Whole-exome sequencing