Title | FixItFelix: improving genomic analysis by fixing reference errors. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Behera, S, LeFaive, J, Orchard, P, Mahmoud, M, Paulin, LF, Farek, J, Soto, DC, Parker, SCJ, Smith, AV, Dennis, MY, Zook, JM, Sedlazeck, FJ |
Journal | Genome Biol |
Volume | 24 |
Issue | 1 |
Pagination | 31 |
Date Published | 2023 Feb 21 |
ISSN | 1474-760X |
Keywords | Genome, Human, Genomics, High-Throughput Nucleotide Sequencing, Humans, Sequence Analysis, DNA |
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. |
DOI | 10.1186/s13059-023-02863-7 |
Alternate Journal | Genome Biol |
PubMed ID | 36810122 |
PubMed Central ID | PMC9942314 |
Grant List | DP2 MH119424 / MH / NIMH NIH HHS / United States 1U01HG011758-01 / HG / NHGRI NIH HHS / United States U01 AG058589 / AG / NIA NIH HHS / United States UM1HG008898 / HG / NHGRI NIH HHS / United States |