Apr 2, 2020

Characterizing sensitivity and coverage of clinical WGS as a diagnostic test for genetic disorders

BioRxiv : the Preprint Server for Biology
Y. SunZhiyu Peng

Abstract

Background: With the reduce of cost and incomparable advantages, WGS is likely to change the way of clinical diagnosis of rare and undiagnosed diseases. However, the sensitivity and breadth of coverage of clinical WGS as a diagnostic test for genetic disorders has not been fully evaluated, especially for CNV detection. Methods: All the samples underwent WGS using MGISEQ-2000. The performance of NA12878, YH cell line, and the Chinese trios were measured for sensitivity, PPV, depth and breadth of coverage. We also compared the performance of WES and WGS using NA12878. The sensitivity and PPV were tested using family-based trio design in the Chinese trios. We also developed a systematic WGS pipeline for the analysis of 8 clinical cases with known disease-causing variants. Results: In general, the sensitivity and PPV for SNV/indel detection increased with mean depth, and reached a plateau at a ~40X mean depth using down-sampling samples of NA12878. With a mean depth of 40X, the sensitivity of homozyous and heterozygous SNPs of NA12878 was >99.25% and >99.50% respectively, and PPVs were 99.97% and 98.96%. Homozygous and heterozygous indels showed lower sensitivity and PPV. The sensitivity and PPV is still not 100% even with a mean d...Continue Reading

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Mentioned in this Paper

In Vivo
HEK293 Cells
Protein Destabilization
Pluripotent Stem Cells
Genome
CRISPR-Cas Systems
RNA, Double-Stranded
Gene Deletion
Fluorescent stain
Excision

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