Library-free methylation sequencing with bisulfite padlock probes

Journal name:
Nature Methods
Year published:
Published online

Targeted quantification of DNA methylation allows for interrogation of the most informative loci across many samples quickly and cost-effectively. Here we report improved bisulfite padlock probes (BSPPs) with a design algorithm to generate efficient padlock probes, a library-free protocol that dramatically reduces sample-preparation cost and time and is compatible with automation, and an efficient bioinformatics pipeline to accurately obtain both methylation levels and genotypes from sequencing of bisulfite-converted DNA.


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Author information

  1. These authors contributed equally to this work.

    • Dinh Diep,
    • Nongluk Plongthongkum &
    • Athurva Gore


  1. Department of Bioengineering, University of California at San Diego, La Jolla, California, USA.

    • Dinh Diep,
    • Nongluk Plongthongkum,
    • Athurva Gore,
    • Ho-Lim Fung &
    • Kun Zhang
  2. Bioinformatics and System Biology Graduate Program, University of California at San Diego, La Jolla, California, USA.

    • Dinh Diep &
    • Kun Zhang
  3. Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California, USA.

    • Robert Shoemaker


K.Z. oversaw the project. D.D. and N.P. performed experiments and bioinformatic analyses. A.G. developed a probe design algorithm. R.S. and A.G. designed probes. H.-L.F. performed sequencing. D.D., N.P., A.G. and K.Z. wrote the manuscript.

Competing financial interests

K.Z. is a paid consultant for Pathogenica Inc. R.S. is a current employee of Illumina Inc.

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