title: Single-molecule optical genome mapping of a human HapMap and a colorectal cancer cell line.
abstract: BACKGROUND
  Next-generation sequencing (NGS) technologies have changed our understanding of the variability of the human genome. However, the identification of genome structural variations based on NGS approaches with read lengths of 35-300 bases remains a challenge. Single-molecule optical mapping technologies allow the analysis of DNA molecules of up to 2 Mb and as such are suitable for the identification of large-scale genome structural variations, and for de novo genome assemblies when combined with short-read NGS data. Here we present optical mapping data for two human genomes: the HapMap cell line GM12878 and the colorectal cancer cell line HCT116.
  
  
  RESULTS
  High molecular weight DNA was obtained by embedding GM12878 and HCT116 cells, respectively, in agarose plugs, followed by DNA extraction under mild conditions. Genomic DNA was digested with KpnI and 310,000 and 296,000 DNA molecules (≥ 150 kb and 10 restriction fragments), respectively, were analyzed per cell line using the Argus optical mapping system. Maps were aligned to the human reference by OPTIMA, a new glocal alignment method. Genome coverage of 6.8× and 5.7× was obtained, respectively; 2.9× and 1.7× more than the coverage obtained with previously available software.
  
  
  CONCLUSIONS
  Optical mapping allows the resolution of large-scale structural variations of the genome, and the scaffold extension of NGS-based de novo assemblies. OPTIMA is an efficient new alignment method; our optical mapping data provide a resource for genome structure analyses of the human HapMap reference cell line GM12878, and the colorectal cancer cell line HCT116.
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672 Singapore.
authors.forename: Audrey S M
authors.initials: AS
authors.lastname: Teo
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672 Singapore.
authors.forename: Davide
authors.initials: D
authors.lastname: Verzotto
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672 Singapore.
authors.forename: Fei
authors.initials: F
authors.lastname: Yao
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672 Singapore.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Nagarajan
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672 Singapore.
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
mesh_terms: D045744:Cell Line, Tumor; D002874:Chromosome Mapping / Q000379:methods; D015179:Colorectal Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm; D015894:Genome, Human; D060148:HapMap Project; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004273:DNA, Neoplasm
keywords: Cancer genome; Genome structure; Genomic mapping; Optical mapping; Single-molecule restriction mapping