title: Towards accurate characterization of clonal heterogeneity based on structural variation.
abstract: BACKGROUND
  Recent advances in deep digital sequencing have unveiled an unprecedented degree of clonal heterogeneity within a single tumor DNA sample. Resolving such heterogeneity depends on accurate estimation of fractions of alleles that harbor somatic mutations. Unlike substitutions or small indels, structural variants such as deletions, duplications, inversions and translocations involve segments of DNAs and are potentially more accurate for allele fraction estimations. However, no systematic method exists that can support such analysis.
  
  
  RESULTS
  In this paper, we present a novel maximum-likelihood method that estimates allele fractions of structural variants integratively from various forms of alignment signals. We develop a tool, BreakDown, to estimate the allele fractions of most structural variants including medium size (from 1 kilobase to 1 megabase) deletions and duplications, and balanced inversions and translocations.
  
  
  CONCLUSIONS
  Evaluation based on both simulated and real data indicates that our method systematically enables structural variants for clonal heterogeneity analysis and can greatly enhance the characterization of genomically instable tumors.
authors.forename: Xian
authors.initials: X
authors.lastname: Fan
authors.forename: Wanding
authors.initials: W
authors.lastname: Zhou
authors.forename: Zechen
authors.initials: Z
authors.lastname: Chong
authors.forename: Luay
authors.initials: L
authors.lastname: Nakhleh
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas M,D, Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. kchen3@mdanderson.org.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
mesh_terms: D000483:Alleles; D058674:Chromosome Duplication / Q000235:genetics; D007446:Chromosome Inversion / Q000235:genetics; D002999:Clone Cells / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016013:Likelihood Functions; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA / Q000379:methods*; D017384:Sequence Deletion / Q000235:genetics; D012984:Software
chemical_list: D004247:DNA