Systematic biases in DNA copy number originate from isolation procedures

S. van Heesch; M. Mokry; V. Boskova; W. Junker; R. Mehon; P. Toonen; E. de Bruijn; J.D. Shull; T.J. Aitman; E. Cuppen; V. Guryev

doi:10.1186/gb-2013-14-4-r33

Systematic biases in DNA copy number originate from isolation procedures

S. van Heesch, M. Mokry, V. Boskova, W. Junker, R. Mehon, P. Toonen, E. de Bruijn, J.D. Shull, T.J. Aitman, E. Cuppen, V. Guryev

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

35 Citations (Scopus)

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 language	English
Pages (from-to)	33
Journal	Genome Biology
Volume	14
Issue number	4
DOIs	https://doi.org/10.1186/gb-2013-14-4-r33
Publication status	Published - 2013

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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. 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.",

author = "{van Heesch}, S. and M. Mokry and V. Boskova and W. Junker and R. Mehon and P. Toonen and {de Bruijn}, E. and J.D. Shull and T.J. Aitman and E. Cuppen and V. Guryev",

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TY - JOUR

T1 - Systematic biases in DNA copy number originate from isolation procedures

AU - van Heesch, S.

AU - Mokry, M.

AU - Boskova, V.

AU - Junker, W.

AU - Mehon, R.

AU - Toonen, P.

AU - de Bruijn, E.

AU - Shull, J.D.

AU - Aitman, T.J.

AU - Cuppen, E.

AU - Guryev, V.

N1 - Reporting year: 2013

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.1186/gb-2013-14-4-r33

DO - 10.1186/gb-2013-14-4-r33

M3 - Article

SN - 1474-760X

VL - 14

SP - 33

JO - Genome Biology

JF - Genome Biology

IS - 4

ER -

Systematic biases in DNA copy number originate from isolation procedures

Abstract

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