trioPhaser: using Mendelian inheritance logic to improve genomic phasing of trios

Abstract Background When analyzing DNA sequence data of an individual, knowing which nucleotide was inherited from each parent can be beneficial when trying to identify certain types of DNA variants. Mendelian inheritance logic can be used to accurately phase (haplotype) the majority (67–83%) of an...

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Autores principales:	Dustin B. Miller, Stephen R. Piccolo
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Haplotyping Phasing Trios Genomics Next-generation sequencing Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/eacc17a6255743e0bcce198e32b06779
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spelling	oai:doaj.org-article:eacc17a6255743e0bcce198e32b067792021-11-28T12:11:00ZtrioPhaser: using Mendelian inheritance logic to improve genomic phasing of trios10.1186/s12859-021-04470-41471-2105https://doaj.org/article/eacc17a6255743e0bcce198e32b067792021-11-01T00:00:00Zhttps://doi.org/10.1186/s12859-021-04470-4https://doaj.org/toc/1471-2105Abstract Background When analyzing DNA sequence data of an individual, knowing which nucleotide was inherited from each parent can be beneficial when trying to identify certain types of DNA variants. Mendelian inheritance logic can be used to accurately phase (haplotype) the majority (67–83%) of an individual's heterozygous nucleotide positions when genotypes are available for both parents (trio). However, when all members of a trio are heterozygous at a position, Mendelian inheritance logic cannot be used to phase. For such positions, a computational phasing algorithm can be used. Existing phasing algorithms use a haplotype reference panel, sequencing reads, and/or parental genotypes to phase an individual; however, they are limited in that they can only phase certain types of variants, require a specific genotype build, require large amounts of storage capacity, and/or require long run times. We created trioPhaser to address these challenges. Results trioPhaser uses gVCF files from an individual and their parents as initial input, and then outputs a phased VCF file. Input trio data are first phased using Mendelian inheritance logic. Then, the positions that cannot be phased using inheritance information alone are phased by the SHAPEIT4 phasing algorithm. Using whole-genome sequencing data of 52 trios, we show that trioPhaser, on average, increases the total number of phased positions by 21.0% and 10.5%, respectively, when compared to the number of positions that SHAPEIT4 or Mendelian inheritance logic can phase when either is used alone. In addition, we show that the accuracy of the phased calls output by trioPhaser are similar to linked-read and read-backed phasing. Conclusion trioPhaser is a containerized software tool that uses both Mendelian inheritance logic and SHAPEIT4 to phase trios when gVCF files are available. By implementing both phasing methods, more variant positions are phased compared to what either method is able to phase alone.Dustin B. MillerStephen R. PiccoloBMCarticleHaplotypingPhasingTriosGenomicsNext-generation sequencingComputer applications to medicine. Medical informaticsR858-859.7Biology (General)QH301-705.5ENBMC Bioinformatics, Vol 22, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Haplotyping Phasing Trios Genomics Next-generation sequencing Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5
spellingShingle	Haplotyping Phasing Trios Genomics Next-generation sequencing Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5 Dustin B. Miller Stephen R. Piccolo trioPhaser: using Mendelian inheritance logic to improve genomic phasing of trios
description	Abstract Background When analyzing DNA sequence data of an individual, knowing which nucleotide was inherited from each parent can be beneficial when trying to identify certain types of DNA variants. Mendelian inheritance logic can be used to accurately phase (haplotype) the majority (67–83%) of an individual's heterozygous nucleotide positions when genotypes are available for both parents (trio). However, when all members of a trio are heterozygous at a position, Mendelian inheritance logic cannot be used to phase. For such positions, a computational phasing algorithm can be used. Existing phasing algorithms use a haplotype reference panel, sequencing reads, and/or parental genotypes to phase an individual; however, they are limited in that they can only phase certain types of variants, require a specific genotype build, require large amounts of storage capacity, and/or require long run times. We created trioPhaser to address these challenges. Results trioPhaser uses gVCF files from an individual and their parents as initial input, and then outputs a phased VCF file. Input trio data are first phased using Mendelian inheritance logic. Then, the positions that cannot be phased using inheritance information alone are phased by the SHAPEIT4 phasing algorithm. Using whole-genome sequencing data of 52 trios, we show that trioPhaser, on average, increases the total number of phased positions by 21.0% and 10.5%, respectively, when compared to the number of positions that SHAPEIT4 or Mendelian inheritance logic can phase when either is used alone. In addition, we show that the accuracy of the phased calls output by trioPhaser are similar to linked-read and read-backed phasing. Conclusion trioPhaser is a containerized software tool that uses both Mendelian inheritance logic and SHAPEIT4 to phase trios when gVCF files are available. By implementing both phasing methods, more variant positions are phased compared to what either method is able to phase alone.
format	article
author	Dustin B. Miller Stephen R. Piccolo
author_facet	Dustin B. Miller Stephen R. Piccolo
author_sort	Dustin B. Miller
title	trioPhaser: using Mendelian inheritance logic to improve genomic phasing of trios
title_short	trioPhaser: using Mendelian inheritance logic to improve genomic phasing of trios
title_full	trioPhaser: using Mendelian inheritance logic to improve genomic phasing of trios
title_fullStr	trioPhaser: using Mendelian inheritance logic to improve genomic phasing of trios
title_full_unstemmed	trioPhaser: using Mendelian inheritance logic to improve genomic phasing of trios
title_sort	triophaser: using mendelian inheritance logic to improve genomic phasing of trios
publisher	BMC
publishDate	2021
url	https://doaj.org/article/eacc17a6255743e0bcce198e32b06779
work_keys_str_mv	AT dustinbmiller triophaserusingmendelianinheritancelogictoimprovegenomicphasingoftrios AT stephenrpiccolo triophaserusingmendelianinheritancelogictoimprovegenomicphasingoftrios
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trioPhaser: using Mendelian inheritance logic to improve genomic phasing of trios

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