CANOES: detecting rare copy number variants from whole exome sequencing data.
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.
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.
Daniel
D
Backenroth
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Jason
J
Homsy
Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Laura R
LR
Murillo
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Joe
J
Glessner
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.
Edwin
E
Lin
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Martina
M
Brueckner
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA Howard Hughes Medical Institute, Yale University, New Haven, CT 06510, USA.
Richard
R
Lifton
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Elizabeth
E
Goldmuntz
Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY 10032, USA ys2411@columbia.edu.
Wendy K
WK
Chung
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.
Yufeng
Y
Shen
D000465:Algorithms; D056915:DNA Copy Number Variations; D059472:Exome; D060005:Genotyping Techniques; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D017422:Sequence Analysis, DNA