Systematic biases in DNA copy number originate from isolation procedures

Sebastiaan van Heesch, Michal Mokry, Veronika Boskova, Wade Junker, Rajdeep Mehon, Pim Toonen, Ewart de Bruijn, James D Shull, Timothy J Aitman, Edwin Cuppen, Victor Guryev

Research output: Contribution to journalArticleAcademicpeer-review

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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.

CONCLUSION: 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.

Original languageEnglish
Article numberR33
Number of pages9
JournalGenome Biology
Volume14
Issue number4
DOIs
Publication statusPublished - 24-Apr-2013

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