CANOES: detecting rare copy number variants from whole exome sequencing data

Daniel Backenroth; Jason Homsy; Laura R Murillo; Joe Glessner; Edwin Lin; Martina Brueckner; Richard Lifton; Elizabeth Goldmuntz; Wendy K Chung; Yufeng Shen

doi:10.1093/nar/gku345

CANOES: detecting rare copy number variants from whole exome sequencing data

Nucleic Acids Res. 2014 Jul;42(12):e97. doi: 10.1093/nar/gku345. Epub 2014 Apr 25.

Authors

Affiliations

¹ Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA JP Sulzberger Columbia Genome Center, Columbia University Medical Center, New York, NY 10032, USA.
² Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
³ Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁴ Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁵ Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY 10032, USA.
⁶ Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
⁷ Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA Howard Hughes Medical Institute, Yale University, New Haven, CT 06510, USA.
⁸ Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
⁹ Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY 10032, USA ys2411@columbia.edu.
¹⁰ Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA JP Sulzberger Columbia Genome Center, Columbia University Medical Center, New York, NY 10032, USA ys2411@columbia.edu.

Abstract

We present CANOES, an algorithm for the detection of rare copy number variants from exome sequencing data. CANOES models read counts using a negative binomial distribution and estimates variance of the read counts using a regression-based approach based on selected reference samples in a given dataset. We test CANOES on a family-based exome sequencing dataset, and show that its sensitivity and specificity is comparable to that of XHMM. Moreover, the method is complementary to Gaussian approximation-based methods (e.g. XHMM or CoNIFER). When CANOES is used in combination with these methods, it will be possible to produce high accuracy calls, as demonstrated by a much reduced and more realistic de novo rate in results from trio data.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Algorithms*
DNA Copy Number Variations*
Exome*
Genotyping Techniques
High-Throughput Nucleotide Sequencing*
Humans
Oligonucleotide Array Sequence Analysis
Sequence Analysis, DNA*

Abstract

Publication types

MeSH terms

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