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  The allele distribution in next-generation sequencing data sets is accurately described as the result of a stochastic branching process

Heinrich, V., Stange, J., Dickhaus, T., Imkeller, P., Kruger, U., Bauer, S., et al. (2011). The allele distribution in next-generation sequencing data sets is accurately described as the result of a stochastic branching process. Nucleic Acids Res. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22127862 http://nar.oxfordjournals.org/content/early/2011/11/29/nar.gkr1073.full.pdf.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-784C-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-784D-6
Genre: Journal Article

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Heinrich, V., Author
Stange, J., Author
Dickhaus, T., Author
Imkeller, P., Author
Kruger, U., Author
Bauer, S., Author
Mundlos, S.1, Author              
Robinson, P. N.1, Author              
Hecht, J.1, Author              
Krawitz, P. M., Author
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

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 Abstract: With the availability of next-generation sequencing (NGS) technology, it is expected that sequence variants may be called on a genomic scale. Here, we demonstrate that a deeper understanding of the distribution of the variant call frequencies at heterozygous loci in NGS data sets is a prerequisite for sensitive variant detection. We model the crucial steps in an NGS protocol as a stochastic branching process and derive a mathematical framework for the expected distribution of alleles at heterozygous loci before measurement that is sequencing. We confirm our theoretical results by analyzing technical replicates of human exome data and demonstrate that the variance of allele frequencies at heterozygous loci is higher than expected by a simple binomial distribution. Due to this high variance, mutation callers relying on binomial distributed priors are less sensitive for heterozygous variants that deviate strongly from the expected mean frequency. Our results also indicate that error rates can be reduced to a greater degree by technical replicates than by increasing sequencing depth.

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 Dates: 2011
 Publication Status: Published in print
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Title: Nucleic Acids Res
Source Genre: Journal
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Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1362-4962 (Electronic) 0305-1048 (Linking)