Predicting the molecular complexity of sequencing libraries

Timothy Daley; Andrew D Smith

doi:10.1038/nmeth.2375

Published: 24 February 2013

Predicting the molecular complexity of sequencing libraries

Timothy Daley¹ &
Andrew D Smith²

Nature Methods volume 10, pages325–327(2013)Cite this article

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Abstract

Predicting the molecular complexity of a genomic sequencing library is a critical but difficult problem in modern sequencing applications. Methods to determine how deeply to sequence to achieve complete coverage or to predict the benefits of additional sequencing are lacking. We introduce an empirical Bayesian method to accurately characterize the molecular complexity of a DNA sample for almost any sequencing application on the basis of limited preliminary sequencing.

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**Figure 1: Difficulties in predicting library complexity from initial shallow sequencing.**

**Figure 2: Library complexity can be estimated in terms of distinct molecules sequenced or distinct loci identified.**

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Acknowledgements

We thank S. Tavaré, M. Waterman, P. Calabrese, G. Hannon, and members of the Hannon lab and the Smith lab for their help, advice and input. This work was supported by US National Institutes of Health National Human Genome Research Institute grants (R01 HG005238 and P50 HG002790).

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Affiliations

Department of Mathematics, University of Southern California, Los Angeles, California, USA
Timothy Daley
Molecular and Computational Biology, University of Southern California, Los Angeles, California, USA
Andrew D Smith

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Timothy Daley
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Andrew D Smith
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Contributions

T.D. and A.D.S. designed the method, implemented the software, performed the analysis and wrote the manuscript.

Corresponding author

Correspondence to Andrew D Smith.

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The authors declare no competing financial interests.

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Daley, T., Smith, A. Predicting the molecular complexity of sequencing libraries. Nat Methods 10, 325–327 (2013). https://doi.org/10.1038/nmeth.2375

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Received: 23 October 2012
Accepted: 18 January 2013
Published: 24 February 2013
Issue Date: April 2013
DOI: https://doi.org/10.1038/nmeth.2375