title: Determination of genomic copy number alteration emphasizing a restriction site-based strategy of genome re-sequencing.
abstract: BACKGROUND
  Copy number abbreviation (CNA) is one type of genomic aberration that is often induced by genome instability and is associated with diseases such as cancer. Determination of the genome-wide CNA profile is an important step in identifying the underlying mutation mechanisms. Genomic data based on next-generation sequencing technology are particularly suitable for determination of high-quality CNA profile. Now is an important time to reevaluate the use of sequencing techniques for CNA analysis, especially with the rapid growth of the different targeted genome and whole-genome sequencing strategies.
  
  
  RESULTS
  In this study, we provide a comparison of resequencing strategies, with regard to their utility, applied to the same hepatocellular carcinoma sample for copy number determination. These strategies include whole-genome, exome and restriction site-associated DNA (RAD) sequencing. The last of these strategies is a targeted sequencing technique that involves cutting the genome with a restriction enzyme and isolating the targeted sequences. Our data demonstrate that RAD sequencing is an efficient and comprehensive strategy that allows the cost-effective determination of CNAs. Further investigation of RAD sequencing data led to the finding that a precise measurement of the allele frequency would be a helpful complement to the read depth for CNA analysis for two reasons. First, knowledge of the allele frequency helps to resolve refined calculations of allele-specific copy numbers, which, in turn, identify the functionally important CNAs that are under natural selection on the parental alleles. Second, this knowledge enables deconvolution of CNA patterns in complex genomic regions.
authors: Laboratory of Disease Genomics and Personalized Medicine & Center of Computational Biology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China, University of Chinese Academy of Sciences, Beijing 100049, China, Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA, Department of Epidemiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100730, China and Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637, USA.
authors: Caihong
authors: C
authors: Zheng
authors: Xuexia
authors: X
authors: Miao
authors: Yanen
authors: Y
authors: Li
authors: Ying
authors: Y
authors: Huang
authors: Jue
authors: J
authors: Ruan
authors: Xi
authors: X
authors: Ma
authors: Li
authors: L
authors: Wang
authors: Chung-I
authors: CI
authors: Wu
authors: Jun
authors: J
authors: Cai
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D056915:DNA Copy Number Variations; D004262:DNA Restriction Enzymes; D059472:Exome; D005260:Female; D005787:Gene Frequency; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004262:DNA Restriction Enzymes