Renal biomarker qualification submission: A dialog between the FDA-EMEA and Predictive Safety Testing Consortium

Frank Dieterle, Frank Sistare, Federico Goodsaid, Marisa Papaluca, Josef S. Ozer, Craig P. Webb, William Baer, Anthony Senagore, Matthew J. Schipper, Jacky Vonderscher, Stefan Sultana, David L. Gerhold, Jonathan A. Phillips, Gérard Maurer, Kevin Carl, David Laurie, Ernie Harpur, Manisha Sonee, Daniela Ennulat, Dan HolderDina Andrews-Cleavenger, Yi Zhong Gu, Karol L. Thompson, Peter L. Goering, Jean Marc Vidal, Eric Abadie, Romaldas MacIulaitis, David Jacobson-Kram, Albert F. Defelice, Elizabeth A. Hausner, Melanie Blank, Aliza Thompson, Patricia Harlow, Douglas Throckmorton, Shen Xiao, Nancy Xu, William Taylor, Spiros Vamvakas, Bruno Flamion, Beatriz Silva Lima, Peter Kasper, Markku Pasanen, Krishna Prasad, Sean Troth, Denise Bounous, Denise Robinson-Gravatt, Graham Betton, Myrtle A. Davis, Jackie Akunda, James Eric McDuffie, Laura Suter, Leslie Obert, Magalie Guffroy, Mark Pinches, Supriya Jayadev, Eric A. Blomme, Sven A. Beushausen, Valérie G. Barlow, Nathaniel Collins, Jeff Waring, David Honor, Sandra Snook, Jinhe Lee, Phil Rossi, Elizabeth Walker, William Mattes

Research output: Contribution to journalReview articlepeer-review

374 Scopus citations


Epigenetic regulation in insects may have effects on diverse biological processes. Here we survey the methylome of a model insect, the silkworm Bombyx mori, at single-base resolution using Illumina high-throughput bisulfite sequencing (MethylC-Seq). We conservatively estimate that 0.11% of genomic cytosines are methylcytosines, all of which probably occur in CG dinucleotides. CG methylation is substantially enriched in gene bodies and is positively correlated with gene expression levels, suggesting it has a positive role in gene transcription. We find that transposable elements, promoters and ribosomal DNAs are hypomethylated, but in contrast, genomic loci matching small RNAs in gene bodies are densely methylated. This work contributes to our understanding of epigenetics in insects, and in contrast to previous studies of the highly methylated genomes of Arabidopsis and human, demonstrates a strategy for sequencing the epigenomes of organisms such as insects that have low levels of methylation.

Original languageEnglish (US)
Pages (from-to)455-462
Number of pages8
JournalNature Biotechnology
Issue number5
StatePublished - May 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering


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