Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Alta-Cyclic: a self-optimizing base caller for next-generation sequencing

Abstract

Next-generation sequencing is limited to short read lengths and by high error rates. We systematically analyzed sources of noise in the Illumina Genome Analyzer that contribute to these high error rates and developed a base caller, Alta-Cyclic, that uses machine learning to compensate for noise factors. Alta-Cyclic substantially improved the number of accurate reads for sequencing runs up to 78 bases and reduced systematic biases, facilitating confident identification of sequence variants.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic representation of main Illumina noise factors.
Figure 2: Alta-Cyclic base caller data flow.
Figure 3: Comparison between Alta-Cyclic and Illumina base caller on the GAII platform.

Similar content being viewed by others

References

  1. Pennisi, E. Science 318, 1842–1843 (2007).

    Article  CAS  Google Scholar 

  2. Chi, K.R. Nat. Methods 5, 11–14 (2008).

    Article  CAS  Google Scholar 

  3. Korbel, J.O. et al. Science 318, 420–426 (2007).

    Article  CAS  Google Scholar 

  4. Hillier, L.W. et al. Nat. Methods 5, 183–188 (2008).

    Article  CAS  Google Scholar 

  5. Cokus, S.J. et al. Nature 452, 215–219 (2008).

    Article  CAS  Google Scholar 

  6. Whiteford, N. et al. Nucleic Acids Res. 33, e171 (2005).

    Article  Google Scholar 

  7. Chaisson, M. & Pevzner, P. Genome Res. 18, 324–330 (2008).

    Article  CAS  Google Scholar 

  8. Metzker, M. Genome Res. 15, 1767–1776 (2005).

    Article  CAS  Google Scholar 

  9. Metzker, M., Raghavachari, R., Burgess, K. & Gibbs, R. Biotechniques 25, 814–817 (1998).

    Article  CAS  Google Scholar 

  10. Eisen, J.A. et al. PLoS Biol. 4, e286 (2006).

    Article  Google Scholar 

Download references

Acknowledgements

We thank M. Rooks, E. Hodges, K. Fejes-Toth and C. Malone for help in preparing libraries. We thank M. Regulski, D. Rebolini and L. Cardone for Illumina sequencing, and T. Heywood for assistance with cluster computing. F. Chen, D. Hillman and J. Eisen (Lawrence Berkeley National Lab) provided the Tetrahymena micronuclear library. Y.E. is a Goldberg-Lindsay Fellow of the Watson School of Biological Sciences. P.P.M. is a Crick-Clay Professor. G.J.H. is an investigator of the Howard Hughes Medical Institute. This work was supported by grants from the US National Institute of Health, the National Science Foundation and the Stanley Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gregory J Hannon.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7, Supplementary Table 1, Supplementary Data, Supplementary Methods (PDF 941 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Erlich, Y., Mitra, P., delaBastide, M. et al. Alta-Cyclic: a self-optimizing base caller for next-generation sequencing. Nat Methods 5, 679–682 (2008). https://doi.org/10.1038/nmeth.1230

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth.1230

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing