Published in

Oxford University Press (OUP), Briefings in Bioinformatics, 5(22), 2021

DOI: 10.1093/bib/bbab069



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Converting single nucleotide variants between genome builds: from cautionary tale to solution

Journal article published in 2021 by Cathal Ormond ORCID, Niamh M. Ryan ORCID, Aiden Corvin ORCID, Elizabeth A. Heron ORCID
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Data provided by SHERPA/RoMEO


Abstract Next-generation sequencing studies are dependent on a high-quality reference genome for single nucleotide variant (SNV) calling. Although the two most recent builds of the human genome are widely used, position information is typically not directly comparable between them. Re-alignment gives the most accurate position information, but this procedure is often computationally expensive, and therefore, tools such as liftOver and CrossMap are used to convert data from one build to another. However, the positions of converted SNVs do not always match SNVs derived from aligned data, and in some instances, SNVs are known to change chromosome when converted. This is a significant problem when compiling sequencing resources or comparing results across studies. Here, we describe a novel algorithm to identify positions that are unstable when converting between human genome reference builds. These positions are detected independent of the conversion tools and are determined by the chain files, which provide a mapping of contiguous positions from one build to another. We also provide the list of unstable positions for converting between the two most commonly used builds GRCh37 and GRCh38. Pre-excluding SNVs at these positions, prior to conversion, results in SNVs that are stable to conversion. This simple procedure gives the same final list of stable SNVs as applying the algorithm and subsequently removing variants at unstable positions. This work highlights the care that must be taken when converting SNVs between genome builds and provides a simple method for ensuring higher confidence converted data. Unstable positions and algorithm code, available at