Pan-human consensus genome significantly improves the accuracy of RNA-seq analyses

Kaminow, Benjamin, Ballouz, Sara, Gillis, Jesse, Dobin, Alexander (March 2022) Pan-human consensus genome significantly improves the accuracy of RNA-seq analyses. Genome Research. gr.275613.121-gr.275613.121. ISSN 1088-9051

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DOI: 10.1101/gr.275613.121


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. We also found that using more population-specific consensuses resulted in little to no increase overusing the pan-human consensus, suggesting a limit in the utility of incorporating more specific genomic variation. Replacing reference with consensus genomes impacts functional analyses, such as differential expressions of isoforms, genes, and splice junctions.

Item Type: Paper
Subjects: Investigative techniques and equipment
Investigative techniques and equipment > assays
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
organism description > animal > mammal > primates > hominids > human
Investigative techniques and equipment > assays > RNA-seq
Investigative techniques and equipment > whole exome sequencing
Investigative techniques and equipment > assays > whole exome sequencing
CSHL Authors:
Communities: CSHL labs > Gillis Lab
CSHL labs > Dobin Lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 7 March 2022
Date Deposited: 10 Mar 2022 14:23
Last Modified: 11 Jan 2024 20:43
PMCID: PMC8997357

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