A Comparison of Tools for Copy-Number Variation Detection in Germline Whole Exome and Whole Genome Sequencing Data.

Autor: Gabrielaite M; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Torp MH; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Rasmussen MS; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Andreu-Sánchez S; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Vieira FG; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Pedersen CB; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.; Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Ørsteds Pl. 345C, 2800 Kgs. Lyngby, Denmark., Kinalis S; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Madsen MB; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Kodama M; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Demircan GS; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Simonyan A; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Yde CW; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Olsen LR; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.; Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Ørsteds Pl. 345C, 2800 Kgs. Lyngby, Denmark., Marvig RL; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Østrup O; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Rossing M; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.; Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark., Nielsen FC; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark., Winther O; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.; Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.; Section for Cognitive Systems, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Matematiktorvet 303B, 2800 Kgs. Lyngby, Denmark., Bagger FO; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.; Department of Biomedicine, UKBB Universitats-Kinderspital Basel, 4031 Basel, Switzerland.; Swiss Institute of Bioinformatics, Hebelstrasse 20, 4031 Basel, Switzerland.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Dec 14; Vol. 13 (24). Date of Electronic Publication: 2021 Dec 14.
DOI: 10.3390/cancers13246283
Abstrakt: Copy-number variations (CNVs) have important clinical implications for several diseases and cancers. Relevant CNVs are hard to detect because common structural variations define large parts of the human genome. CNV calling from short-read sequencing would allow single protocol full genomic profiling. We reviewed 50 popular CNV calling tools and included 11 tools for benchmarking in a reference cohort encompassing 39 whole genome sequencing (WGS) samples paired current clinical standard-SNP-array based CNV calling. Additionally, for nine samples we also performed whole exome sequencing (WES), to address the effect of sequencing protocol on CNV calling. Furthermore, we included Gold Standard reference sample NA12878, and tested 12 samples with CNVs confirmed by multiplex ligation-dependent probe amplification (MLPA). Tool performance varied greatly in the number of called CNVs and bias for CNV lengths. Some tools had near-perfect recall of CNVs from arrays for some samples, but poor precision. Several tools had better performance for NA12878, which could be a result of overfitting. We suggest combining the best tools also based on different methodologies: GATK gCNV, Lumpy, DELLY, and cn.MOPS. Reducing the total number of called variants could potentially be assisted by the use of background panels for filtering of frequently called variants.
Databáze: MEDLINE
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