Print Email Facebook Twitter WISECONDOR: Detection of fetal aberrations from shallow sequencing maternal plasma based on a within-sample comparison scheme Title WISECONDOR: Detection of fetal aberrations from shallow sequencing maternal plasma based on a within-sample comparison scheme Author Straver, R. Sistermans, E.A. Holstege, H. Visser, A. Oudejans, C.B.M. Reinders, M.J.T. Faculty Electrical Engineering, Mathematics and Computer Science Department Intelligent Systems Date 2013-10-28 Abstract Genetic disorders can be detected by prenatal diagnosis using Chorionic Villus Sampling, but the 1:100 chance to result in miscarriage restricts the use to fetuses that are suspected to have an aberration. Detection of trisomy 21 cases noninvasively is now possible owing to the upswing of next-generation sequencing (NGS) because a small percentage of fetal DNA is present in maternal plasma. However, detecting other trisomies and smaller aberrations can only be realized using high-coverage NGS, making it too expensive for routine practice. We present a method, WISECONDOR (WIthin-SamplE COpy Number aberration DetectOR), which detects small aberrations using low-coverage NGS. The increased detection resolution was achieved by comparing read counts within the tested sample of each genomic region with regions on other chromosomes that behave similarly in control samples. This within-sample comparison avoids the need to re-sequence control samples. WISECONDOR correctly identified all T13, T18 and T21 cases while coverages were as low as 0.15–1.66. No false positives were identified. Moreover, WISECONDOR also identified smaller aberrations, down to 20 Mb, such as del(13)(q12.3q14.3), +i(12)(p10) and i(18)(q10). This shows that prevalent fetal copy number aberrations can be detected accurately and affordably by shallow sequencing maternal plasma. WISECONDOR is available at bioinformatics.tudelft.nl/wisecondor. To reference this document use: http://resolver.tudelft.nl/uuid:8307c45c-abd5-403a-8f33-429dccddb819 DOI https://doi.org/10.1093/nar/gkt992 Publisher Oxford University Press ISSN 0305-1048 Source Nucleic Acids Research, 2013 Part of collection Institutional Repository Document type journal article Rights (c)2013 The Author(s)This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Files PDF Straver_2013.pdf 2.58 MB Close viewer /islandora/object/uuid:8307c45c-abd5-403a-8f33-429dccddb819/datastream/OBJ/view