FixItFelix: improving genomic analysis by fixing reference errors

Sairam Behera; Jonathon LeFaive; Peter Orchard; Medhat Mahmoud; Luis F Paulin; Jesse Farek; Daniela C Soto; Stephen C J Parker; Albert V Smith; Megan Y Dennis; Justin M Zook; Fritz J Sedlazeck

doi:10.1186/s13059-023-02863-7

FixItFelix: improving genomic analysis by fixing reference errors

Genome Biol. 2023 Feb 21;24(1):31. doi: 10.1186/s13059-023-02863-7.

Authors

Affiliations

¹ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
² Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
³ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
⁴ Genome Center, MIND Institute, Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, CA, USA.
⁵ Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, USA. justin.zook@nist.gov.
⁶ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA. Fritz.Sedlazeck@bcm.edu.
⁷ Department of Computer Science, Rice University, Houston, TX, USA. Fritz.Sedlazeck@bcm.edu.

Abstract

The current version of the human reference genome, GRCh38, contains a number of errors including 1.2 Mbp of falsely duplicated and 8.04 Mbp of collapsed regions. These errors impact the variant calling of 33 protein-coding genes, including 12 with medical relevance. Here, we present FixItFelix, an efficient remapping approach, together with a modified version of the GRCh38 reference genome that improves the subsequent analysis across these genes within minutes for an existing alignment file while maintaining the same coordinates. We showcase these improvements over multi-ethnic control samples, demonstrating improvements for population variant calling as well as eQTL studies.

Keywords: GIAB; GRCh38; INDEL; Medically relevant genes; Reference; Remapping; SNV; T2T-CHM13; Variant; eQTL.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Genome, Human*
Genomics*
High-Throughput Nucleotide Sequencing
Humans
Sequence Analysis, DNA

Abstract

Publication types

MeSH terms

Grants and funding