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JAX-CNV: A Whole-genome Sequencing-based Algorithm for Copy Number Detection at Clinical Grade Level
- Title
- JAX-CNV: A Whole-genome Sequencing-based Algorithm for Copy Number Detection at Clinical Grade Level
- Authors
- Lee, Wan-Ping; Zhu, Qihui; Yang, Xiaofei; Liu, Silvia; Cerveira, Eliza; Ryan, Mallory; Mil-Homens, Adam; Bellfy, Lauren; Ye, Kai; Lee, Charles; Zhang, Chengsheng
- Ewha Authors
- Charles Lee
- SCOPUS Author ID
- Charles Lee
- Issue Date
- 2022
- Journal Title
- GENOMICS PROTEOMICS & BIOINFORMATICS
- ISSN
- 1672-0229
2210-3244
- Citation
- GENOMICS PROTEOMICS & BIOINFORMATICS vol. 20, no. 6, pp. 1197 - 1206
- Keywords
- Copy number variant; Chromosomal microarray assay; Whole-genome sequencing; JAX-CNV; Genetic testing
- Publisher
- ELSEVIER
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- We aimed to develop a whole-genome sequencing (WGS)-based copy number variant (CNV) calling algorithm with the potential of replacing chromosomal microarray assay (CMA) for clinical diagnosis. JAX-CNV is thus developed for CNV detection from WGS data. The performance of this CNV calling algorithm was evaluated in a blinded manner on 31 samples and compared to the 112 CNVs reported by clinically validated CMAs for these 31 samples. The result showed that JAX-CNV recalled 100% of these CNVs. Besides, JAX-CNV identified an average of 30 CNVs per individual, representing an approximately seven-fold increase compared to calls of clinically validated CMAs. Experimental validation of 24 randomly selected CNVs showed one false positive, i.e., a false discovery rate (FDR) of 4.17%. A robustness test on lower-coverage data revealed a 100% sensitivity for CNVs larger than 300 kb (the current threshold for College of American Pathologists) down to 10x coverage. For CNVs larger than 50 kb, sensitivities were 100% for coverages deeper than 20x, 97% for 15x, and 95% for 10x. We developed a WGS-based CNV pipeline, including this newly developed CNV caller JAX-CNV, and found it capable of detecting CMA-reported CNVs at a sensitivity of 100% with about a FDR of 4%. We propose that JAX-CNV could be further examined in a multi-institutional study to justify the transition of first-tier genetic testing from CMAs to WGS. JAX-CNV is available at https://github.com/TheJacksonLaboratory/JAX-CNV.
- DOI
- 10.1016/j.gpb.2021.06.003
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
- Files in This Item:
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JAX-CNV A Whole-genome Sequencing-based Algorithm for Copy Number Detection at Clinical Grade Level.pdf(1.7 MB)
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