Virtue as the mean: Pan-human consensus genome significantly improves the accuracy of RNA-seq analyses

Kaminow, Benjamin, Ballouz, Sara, Gillis, Jesse, Dobin, Alexander (December 2020) Virtue as the mean: Pan-human consensus genome significantly improves the accuracy of RNA-seq analyses. BioRxiv. (Unpublished)

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Abstract

The Human Reference Genome serves as the foundation for modern genomic analyses. However, in its present form, it does not adequately represent the vast genetic diversity of the human population. In this study, we explored the consensus genome as a potential successor of the current Reference genome and assessed its effect on the accuracy of RNA-seq read alignment. In order to find the best haploid genome representation, we constructed consensus genomes at the Pan-human, Super-population and Population levels, utilizing variant information from the 1000 Genomes project. Using personal haploid genomes as the ground truth, we compared mapping errors for real RNA-seq reads aligned to the consensus genomes versus the Reference genome. For reads overlapping homozygous variants, we found that the mapping error decreased by a factor of ~2-3 when the Reference was replaced with the Pan-human consensus genome. Interestingly, we also found that using more population-specific consensuses resulted in little to no increase over using the Pan-human consensus, suggesting a limit in the utility of incorporating more specific genomic variation. To assess the functional impact, we compared splice junction expression in the different genomes and found that the Pan-human consensus increases accuracy of splice junction quantification for hundreds of splice junctions.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes organism description > animal > mammal > primates > hominids > human
CSHL Authors:	Ballouz, Sara Gillis, Jesse Dobin, Alexander Kaminow, Benjamin
Communities:	CSHL labs > Gillis Lab CSHL labs > Dobin Lab CSHL Post Doctoral Fellows
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	22 December 2020
Date Deposited:	07 May 2021 19:33
Last Modified:	29 Oct 2025 19:09
URI:	https://repository.cshl.edu/id/eprint/40061

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