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 [email protected].
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 [email protected].

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

Grants and funding