Abstract
BackgroundThe 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.ResultsWhile 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.ConclusionThese 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.
Highlights
The ability to accurately detect DNA copy number variation in both a sensitive and quantitative manner is important in many research areas
While the detection of copy number variation (CNV) previously relied on low resolution techniques like quantitative polymerase chain reaction (PCR) or multiplex ligationdependent probe amplification (MLPA), high-resolution array-based comparative genomic hybridization and next-generation sequencing (NGS)-based depth of read coverage (DOC) approaches [1] allow for detailed genome-wide analyses
We demonstrate that DNA isolation procedures can introduce a systematic bias that contributes to the wave effects in array-based comparative genomic hybridization (aCGH) data and the variation in coverage depth in NGS data
Summary
The ability to accurately detect DNA copy number variation in both a sensitive and quantitative manner is important in many research areas. The ability to accurately detect DNA copy number variation (CNV) in both a sensitive and quantitative manner is important in many research areas. While the detection of CNVs previously relied on low resolution techniques like quantitative PCR or MLPA, high-resolution array-based comparative genomic hybridization (aCGH) and next-generation sequencing (NGS)-based depth of read coverage (DOC) approaches [1] allow for detailed genome-wide analyses. Both aCGH and DOC are complicated by the presence of ‘wave patterns’ in the raw data where the measurement deviates systematically from equimolar representation.
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