Journal article
CNV-ROC: A cost effective, computer-aided analytical performance evaluator of chromosomal microarrays
Journal of biomedical informatics, Vol.54, pp.106-113
04/2015
DOI: 10.1016/j.jbi.2015.01.001
PMCID: PMC4936396
PMID: 25595567
Abstract
[Display omitted]
•Chromosomal microarrays (CMAs) are important research and diagnostic tools.•CNV-ROC is a software tool that can aid in the evaluation of CMA platforms.•CNV-ROC uses a per-probe approach for comparison of copy number variants (CNVs).•CNV-ROC calculates genome-wide true and false positive and negative results.•CNV-ROC can use both unique and common, polymorphic CNVs.
Chromosomal microarrays (CMAs) are routinely used in both research and clinical laboratories; yet, little attention has been given to the estimation of genome-wide true and false negatives during the assessment of these assays and how such information could be used to calibrate various algorithmic metrics to improve performance. Low-throughput, locus-specific methods such as fluorescence in situ hybridization (FISH), quantitative PCR (qPCR), or multiplex ligation-dependent probe amplification (MLPA) preclude rigorous calibration of various metrics used by copy number variant (CNV) detection algorithms. To aid this task, we have established a comparative methodology, CNV-ROC, which is capable of performing a high throughput, low cost, analysis of CMAs that takes into consideration genome-wide true and false negatives. CNV-ROC uses a higher resolution microarray to confirm calls from a lower resolution microarray and provides for a true measure of genome-wide performance metrics at the resolution offered by microarray testing. CNV-ROC also provides for a very precise comparison of CNV calls between two microarray platforms without the need to establish an arbitrary degree of overlap. Comparison of CNVs across microarrays is done on a per-probe basis and receiver operator characteristic (ROC) analysis is used to calibrate algorithmic metrics, such as log2 ratio threshold, to enhance CNV calling performance. CNV-ROC addresses a critical and consistently overlooked aspect of analytical assessments of genome-wide techniques like CMAs which is the measurement and use of genome-wide true and false negative data for the calculation of performance metrics and comparison of CNV profiles between different microarray experiments.
Details
- Title: Subtitle
- CNV-ROC: A cost effective, computer-aided analytical performance evaluator of chromosomal microarrays
- Creators
- Corey W Goodman - Department of Electrical and Computer Engineering, The University of Iowa, United StatesHeather J Major - Department of Pediatrics, The University of Iowa, United StatesWilliam D Walls - Department of Electrical and Computer Engineering, The University of Iowa, United StatesVal C Sheffield - Ph.D. Program in Genetics, The University of Iowa, United StatesThomas L Casavant - Department of Electrical and Computer Engineering, The University of Iowa, United StatesBenjamin W Darbro - Department of Pediatrics, The University of Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Journal of biomedical informatics, Vol.54, pp.106-113
- DOI
- 10.1016/j.jbi.2015.01.001
- PMID
- 25595567
- PMCID
- PMC4936396
- NLM abbreviation
- J Biomed Inform
- ISSN
- 1532-0464
- eISSN
- 1532-0480
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 04/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984064224702771
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