title: Systematic biases in DNA copy number originate from isolation procedures.
abstract: BACKGROUND
  The ability to accurately detect DNA copy number variation in both a sensitive and quantitative manner is important in many research areas. However, genome-wide DNA copy number analyses are complicated by variations in detection signal.
  
  
  RESULTS
  While GC content has been used to correct for this, here we show that coverage biases are tissue-specific and independent of the detection method as demonstrated by next-generation sequencing and array CGH. Moreover, we show that DNA isolation stringency affects the degree of equimolar coverage and that the observed biases coincide with chromatin characteristics like gene expression, genomic isochores, and replication timing.
  
  
  CONCLUSIONS
  These results indicate that chromatin organization is a main determinant for differential DNA retrieval. These findings are highly relevant for germline and somatic DNA copy number variation analyses.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: van Heesch
authors.forename: Michal
authors.initials: M
authors.lastname: Mokry
authors.forename: Veronika
authors.initials: V
authors.lastname: Boskova
authors.forename: Wade
authors.initials: W
authors.lastname: Junker
authors.forename: Rajdeep
authors.initials: R
authors.lastname: Mehon
authors.forename: Pim
authors.initials: P
authors.lastname: Toonen
authors.forename: Ewart
authors.initials: E
authors.lastname: de Bruijn
authors.forename: James D
authors.initials: JD
authors.lastname: Shull
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Aitman
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.forename: Victor
authors.initials: V
authors.lastname: Guryev
mesh_terms: D000818:Animals; D016477:Artifacts; D005591:Chemical Fractionation; D004247:DNA / Q000235:genetics / Q000302:isolation & purification*; D056915:DNA Copy Number Variations; D051381:Rats; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods / Q000592:standards
chemical_list: D004247:DNA