A Survey of Genomic Traces Reveals a Common Sequencing

While it is widely held that an organism’s genomic information should remain constant, several protein families are known to modify it. Members of the AID/APOBEC protein family can deaminate DNA. Similarly, members of the ADAR family can deaminate RNA. Characterizing the scope of these events is challenging. Here we use large genomic data sets, such as the two billion sequences in the NCBI Trace Archive, to look for clusters of mismatches of the same type, which are a hallmark of editing events caused by APOBEC3 and ADAR. We align 603,249,815 traces from the NCBI trace archive to their reference genomes. In clusters of mismatches of increasing size, at least one systematic sequencing error dominates the results (G-toA). It is still present in mismatches with 99% accuracy and only vanishes in mismatches at 99.99% accuracy or higher. The error appears to have entered into about 1% of the HapMap, possibly affecting other users that rely on this resource. Further investigation, using stringent quality thresholds, uncovers thousands of mismatch clusters with no apparent defects in their chromatograms. These traces provide the first reported candidates of endogenous DNA editing in human, further elucidating RNA editing in human and mouse and also revealing, for the first time, extensive RNA editing in Xenopus tropicalis. We show that the NCBI Trace Archive provides a valuable resource for the investigation of the phenomena of DNA and RNA editing, as well as setting the stage for a comprehensive mapping of editing events in large-scale genomic datasets. Citation: Zaranek AW, Levanon EY, Zecharia T, Clegg T, Church GM (2010) A Survey of Genomic Traces Reveals a Common Sequencing Error, RNA Editing, and DNA Editing. PLoS Genet 6(5): e1000954. doi:10.1371/journal.pgen.1000954 Editor: Dirk Schübeler, Friedrich Miescher Institute for Biomedical Research, Switzerland Received August 20, 2009; Accepted April 15, 2010; Published May 20, 2010 Copyright: 2010 Zaranek et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: EYL was supported by the Machiah foundation. Funding came from National Human Genome Research Institute Centers of Excellence in Genomic Science grant to GMC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected] (AWZ); [email protected] (EYL) . These authors contributed equally to this work.