{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T02:56:22Z","timestamp":1778900182303,"version":"3.51.4"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":3179,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Although copy-number aberrations are known to contribute to the diversity of the human DNA and cause various diseases, many aberrations and their phenotypes are still to be explored. The recent development of single-nucleotide polymorphism (SNP) arrays provides researchers with tools for calling genotypes and identifying chromosomal aberrations at an order-of-magnitude greater resolution than possible a few years ago. The fundamental problem in array-based copy-number (CN) analysis is to obtain CN estimates at a single-locus resolution with high accuracy and precision such that downstream segmentation methods are more likely to succeed.<\/jats:p>\n               <jats:p>Results: We propose a preprocessing method for estimating raw CNs from Affymetrix SNP arrays. Its core utilizes a multichip probe-level model analogous to that for high-density oligonucleotide expression arrays. We extend this model by adding an adjustment for sequence-specific allelic imbalances such as cross-hybridization between allele A and allele B probes. We focus on total CN estimates, which allows us to further constrain the probe-level model to increase the signal-to-noise ratio of CN estimates. Further improvement is obtained by controlling for PCR effects. Each part of the model is fitted robustly. The performance is assessed by quantifying how well raw CNs alone differentiate between one and two copies on Chromosome X (ChrX) at a single-locus resolution (27kb) up to a 200kb resolution. The evaluation is done with publicly available HapMap data.<\/jats:p>\n               <jats:p>Availability: The proposed method is available as part of an open-source R package named aroma.affymetrix. Because it is a bounded-memory algorithm, any number of arrays can be analyzed.<\/jats:p>\n               <jats:p>Contact: \u00a0hb@stat.berkeley.edu<\/jats:p>\n               <jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn016","type":"journal-article","created":{"date-parts":[[2008,1,20]],"date-time":"2008-01-20T01:13:55Z","timestamp":1200791635000},"page":"759-767","source":"Crossref","is-referenced-by-count":120,"title":["Estimation and assessment of raw copy numbers at the single locus level"],"prefix":"10.1093","volume":"24","author":[{"given":"H.","family":"Bengtsson","sequence":"first","affiliation":[{"name":"1 Department of Statistics, University of California, Berkeley, USA, 2Department of Biostatistics, Johns Hopkins University, Baltimore, USA and 3Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Parkville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Irizarry","sequence":"additional","affiliation":[{"name":"1 Department of Statistics, University of California, Berkeley, USA, 2Department of Biostatistics, Johns Hopkins University, Baltimore, USA and 3Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Parkville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"1 Department of Statistics, University of California, Berkeley, USA, 2Department of Biostatistics, Johns Hopkins University, Baltimore, USA and 3Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Parkville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. P.","family":"Speed","sequence":"additional","affiliation":[{"name":"1 Department of Statistics, University of California, Berkeley, USA, 2Department of Biostatistics, Johns Hopkins University, Baltimore, USA and 3Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Parkville, Australia"},{"name":"1 Department of Statistics, University of California, Berkeley, USA, 2Department of Biostatistics, Johns Hopkins University, Baltimore, USA and 3Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Parkville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,1,19]]},"reference":[{"key":"2023020209520878200_B1","article-title":"CNAT 4.0: Copy number and loss of heterozygosity estimation algorithms for the GeneChip human mapping 10\/50\/100\/250\/500K array set","author":"Affymetrix","year":"2007"},{"key":"2023020209520878200_B2","volume-title":"Affymetrix Genotyping Console 2.0 \u2013 User Manual.","author":"Affymetrix Inc","year":"2007"},{"key":"2023020209520878200_B3","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/nature04226","article-title":"A haplotype map of the human genome","volume":"437","author":"Altshuler","year":"2005","journal-title":"Nature"},{"key":"2023020209520878200_B4","volume-title":"Low-level analysis of microarray data.","author":"Bengtsson","year":"2004"},{"key":"2023020209520878200_B5","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/1471-2105-7-100","article-title":"Methodological study of affine transformations of gene expression data with proposed robust non-parametric multi-dimensional normalization method","volume":"7","author":"Bengtsson","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023020209520878200_B6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/1471-2105-5-177","article-title":"Calibration and assessment of channel-specific biases in microarray data with extended dynamical range","volume":"5","author":"Bengtsson","year":"2004","journal-title":"BMC Bioinfo"},{"key":"2023020209520878200_B7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/bioinformatics\/19.2.185","article-title":"A comparison of normalization methods for high density oligonucleotide array data based on variance and bias","volume":"19","author":"Bolstad","year":"2003","journal-title":"Bioinformatics"},{"key":"2023020209520878200_B8","volume-title":"Low-level analysis of high-density oligonucleotide array data: background, normalization and summarization.","author":"Bolstad","year":"2004"},{"key":"2023020209520878200_B9","article-title":"affyPLM: methods for fitting probe-level models","author":"Bolstad","year":"2007"},{"key":"2023020209520878200_B10","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/biostatistics\/kxl042","article-title":"Exploration, normalization, and genotype calls of high density oligonucleotide SNP array data","volume":"8","author":"Carvalho","year":"2007","journal-title":"Biostatistics"},{"key":"2023020209520878200_B11","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/ng1416","article-title":"Detection of large-scale variation in the human genome","volume":"36","author":"Iafrate","year":"2004","journal-title":"Nature Genet"},{"key":"2023020209520878200_B12","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1093\/nar\/gng015","article-title":"Summaries of Affymetrix GeneChip probe level data","volume":"31","author":"Irizarry","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2023020209520878200_B13","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1016\/j.bbrc.2005.06.040","article-title":"Allelic dosage analysis with genotyping microarrays","volume":"333","author":"Ishikawa","year":"2005","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2023020209520878200_B14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1073\/pnas.98.1.31","article-title":"Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection","volume":"98","author":"Li","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023020209520878200_B15","doi-asserted-by":"crossref","first-page":"6071","DOI":"10.1158\/0008-5472.CAN-05-0465","article-title":"A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays","volume":"65","author":"Nannya","year":"2005","journal-title":"Cancer Res"},{"key":"2023020209520878200_B16","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1101\/gr.5402306","article-title":"High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping","volume":"16","author":"Peiffer","year":"2006","journal-title":"Genome Res"},{"key":"2023020209520878200_B17","volume-title":"R: A language and environment for statistical computing.","author":"R Development Core Team","year":"2007"},{"key":"2023020209520878200_B18","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/nature05329","article-title":"Global variation in copy number in the human genome","volume":"444","author":"Redon","year":"2006","journal-title":"Nature"},{"key":"2023020209520878200_B19","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1126\/science.1098918","article-title":"Large-scale copy number polymorphism in the human genome","volume":"305","author":"Sebat","year":"2004","journal-title":"Science"},{"key":"2023020209520878200_B20","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nature02168","article-title":"The International HapMap Project","volume":"426","author":"The International HapMap Consortium","year":"2003","journal-title":"Nature"},{"key":"2023020209520878200_B21","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1471-2105-7-25","article-title":"Analysis and visualization of chromosomal abnormalities in SNP data with SNPscan","volume":"7","author":"Ting","year":"2006","journal-title":"BMC Bioinfo"},{"key":"2023020209520878200_B22","article-title":"Fitting polyhedrial cones and simplices to multivariate data points","author":"Wirapati","year":"2001"},{"key":"2023020209520878200_B23","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1093\/bioinformatics\/bti665","article-title":"An expression index for Affymetrix GeneChips based on the generalized logarithm","volume":"21","author":"Zhou","year":"2005","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/6\/759\/49048336\/bioinformatics_24_6_759.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/6\/759\/49048336\/bioinformatics_24_6_759.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T10:48:07Z","timestamp":1675334887000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/24\/6\/759\/193223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,19]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2008,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btn016","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,3,15]]},"published":{"date-parts":[[2008,1,19]]}}}