{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:37:07Z","timestamp":1760985427924},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background: Non-invasive detection of aneuploidies in a fetal genome through analysis of cell-free DNA circulating in the maternal plasma is becoming a routine clinical test. Such tests, which rely on analyzing the read coverage or the allelic ratios at single-nucleotide polymorphism (SNP) loci, are not sensitive enough for smaller sub-chromosomal abnormalities due to sequencing biases and paucity of SNPs in a genome.<\/jats:p>\n               <jats:p>Results: We have developed an alternative framework for identifying sub-chromosomal copy number variations in a fetal genome. This framework relies on the size distribution of fragments in a sample, as fetal-origin fragments tend to be smaller than those of maternal origin. By analyzing the local distribution of the cell-free DNA fragment sizes in each region, our method allows for the identification of sub-megabase CNVs, even in the absence of SNP positions. To evaluate the accuracy of our method, we used a plasma sample with the fetal fraction of 13%, down-sampled it to samples with coverage of 10X\u201340X and simulated samples with CNVs based on it. Our method had a perfect accuracy (both specificity and sensitivity) for detecting 5\u2009Mb CNVs, and after reducing the fetal fraction (to 11%, 9% and 7%), it could correctly identify 98.82\u2013100% of the 5\u2009Mb CNVs and had a true-negative rate of 95.29\u201399.76%.<\/jats:p>\n               <jats:p>Availability and implementation: Our source code is available on GitHub at https:\/\/github.com\/compbio-UofT\/FSDA.<\/jats:p>\n               <jats:p>Contact: brudno@cs.toronto.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw178","type":"journal-article","created":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T04:05:31Z","timestamp":1460001931000},"page":"1662-1669","source":"Crossref","is-referenced-by-count":8,"title":["Cell-free DNA fragment-size distribution analysis for non-invasive prenatal CNV prediction"],"prefix":"10.1093","volume":"32","author":[{"given":"Aryan","family":"Arbabi","sequence":"first","affiliation":[{"name":"1 Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada"},{"name":"2 Centre for Computational Medicine, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ladislav","family":"Ramp\u00e1\u0161ek","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada"},{"name":"3 Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Brudno","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada"},{"name":"2 Centre for Computational Medicine, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada and"},{"name":"3 Genetics and Genome Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,4,5]]},"reference":[{"key":"2023020112293182100_btw178-B1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"1000 Genomes Project Consortium","year":"2015","journal-title":"Nature"},{"key":"2023020112293182100_btw178-B2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1373\/clinchem.2003.024893","article-title":"Size distributions of maternal and fetal DNA in maternal plasma","volume":"50","author":"Chan","year":"2004","journal-title":"Clin. 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