wisecondor

BACKGROUND: Non-Invasive Prenatal Testing is often performed by utilizing read coverage-based profiles obtained from shallow whole genome sequencing to detect fetal copy number variations. Such screening typically operates on a discretized binned representation of the genome, where (ab)normality of bins of a set size is judged relative to a reference panel of healthy samples. In practice such approaches are too costly given that for each tested sample they require the resequencing of the reference panel to avoid technical bias...

Background: We aimed to screen tumor-associated functional genes on a large scale through copy number variation (CNV) analysis of papillary thyroid cancer (PTC). Methods: We analyzed 74 tissue samples from 41 patients with thyroid nodules. The samples were subjected to whole-genome resequencing and then analyzed by the 'WISECONDOR' method. Potential chromosome CNV regions were identified between the different sample groups. Results: Of the 74 samples from 41 patients, 28 were PTC tissue samples, 29 were para-carcinoma tissue samples, 13 were benign tumor tissue samples and 4 were para-benign tumor tissue samples...

BACKGROUND: Analysis of cell-free tumour DNA, a liquid biopsy, is a promising biomarker for cancer. We have performed a proof-of principle study to test the applicability in the clinical setting, analysing copy number alterations (CNAs) in plasma and tumour tissue from 44 patients with gastro-oesophageal cancer. METHODS: DNA was isolated from blood plasma and a tissue sample from each patient. Array-CGH was applied to the tissue DNA. The cell-free plasma DNA was sequenced by low-coverage whole-genome sequencing using a clinical pipeline for non-invasive prenatal testing...

BACKGROUND: The detection limit of noninvasive prenatal testing (NIPT) by next generation sequencing for any given fetal copy number variants (CNV) can be influenced by several factors. In this study, we quantified the effects and predicted the value of parameters for CNVs detection by NIPT. METHODS: Genomic DNA from patient's leucocytes with 3.16 Mb microdeletion in 22q11.21 was mixed with DNA from aborted fetal tissues without CNV at various concentrations by an enzyme digestion method...

Shallow whole-genome sequencing to infer copy number alterations (CNAs) in the human genome is rapidly becoming the method par excellence for routine diagnostic use. Numerous tools exist to deduce aberrations from massive parallel sequencing data, yet most are optimized for research and often fail to redeem paramount needs in a clinical setting. Optimally, a read depth-based analytical software should be able to deal with single-end and low-coverage data-this to make sequencing costs feasible. Other important factors include runtime, applicability to a variety of analyses and overall performance...

OBJECTIVE: To validate and evaluate the performance metrics of the high-throughput semiconductor sequencing platform, Ion Proton®, in non-invasive prenatal genetic screening (NIPS) for common fetal aneuploidies in a clinical setting. METHODS: This prospective cohort study included 2505 pregnant women from eight academic genetics laboratories (695 high risk for trisomy 21 (risk ≥ 1/250) pregnancies in a validation study, and 1810 such pregnancies, without ultrasound anomalies, in a real-life NIPS clinical setting)...

OBJECTIVES: We have established an open source platform for non-invasive prenatal testing (NIPT) based on massively parallel whole-genome sequencing in a public setting. The objective of this study was to investigate factors of importance for correct interpretation of NIPT results to ensure a high sensitivity and specificity. STUDY DESIGN: This investigation is a retrospective case-control study performed in a public NIPT center. The study included 108 aneuploid cases and 165 euploid controls...

PURPOSE: Using genome-wide noninvasive prenatal screening (NIPS), we detected a 20-megabase specific deletion starting at 10q25 in eight pregnancies. The deletion could not be confirmed by invasive testing. Since all 10(q25→qter) deletions started close to the FRA10B fragile site in 10q25, we investigated whether the pregnant women were indeed carriers of FRA10B. METHODS: We performed NIPS analysis for all autosomes using single-read sequencing. Analysis was done with the WISECONDOR algorithm...

Minimally Invasive Karyotyping (MINK) was communicated in 2009 as a novel method for the non-invasive detection of fetal copy number anomalies in maternal plasma DNA. The original manuscript illustrated the potential of MINK using a model system in which fragmented genomic DNA obtained from a trisomy 21 male individual was mixed with that of his karyotypically normal mother at dilutions representing fetal fractions found in maternal plasma. Although it has been previously shown that MINK is able to non-invasively detect fetal microdeletions, its utility for aneuploidy detection in maternal plasma has not previously been demonstrated...

BACKGROUND: Non-invasive prenatal testing (NIPT) identifies fetal aneuploidy by sequencing cell-free DNA in the maternal plasma. Pre-symptomatic maternal malignancies have been incidentally detected during NIPT based on abnormal genomic profiles. This low coverage sequencing approach could have potential for ovarian cancer screening in the non-pregnant population. Our objective was to investigate whether plasma DNA sequencing with a clinical whole genome NIPT platform can detect early- and late-stage high-grade serous ovarian carcinomas (HGSOC)...

OBJECTIVE: The objective of this study was to introduce non-invasive prenatal testing (NIPT) for fetal autosomal trisomies and gender in a Danish public health setting, using semi-conductor sequencing and published open source scripts for analysis. METHODS: Plasma-derived DNA from a total of 375 pregnant women (divided into three datasets) was whole-genome sequenced on the Ion Proton™ platform and analyzed using a pipeline based on WISECONDOR for fetal autosomal aneuploidy detection and SeqFF for fetal DNA fraction estimation...

OBJECTIVE: To validate Illumina's two-channel NextSeq 500 sequencing system for noninvasive prenatal testing (NIPT) of fetal whole chromosome and partial aberrations. METHODS: A total of 162 plasma samples, previously sequenced for NIPT on a SOLiD 5500xl platform, were sequenced on the NextSeq 500 using 75-bp single-end sequencing, followed by analysis using the WISECONDOR algorithm. RESULTS: For whole chromosome aneuploidy detection, all samples were classified correctly (in total 3× T13, 3× T18, 8× T21 and 145× euploid)...

Noninvasive prenatal testing is a relatively new screening method for the detection of fetal chromosome abnormalities using next-generation sequencing (NGS) of fetal DNA in maternal blood. Recently, the introduction of a new tool called WIthin SamplE COpy Number aberration DetectOR (WISECONDOR) marked a new era in prenatal screening. WISECONDOR detects copy number aberrations at a resolution that is almost comparable to classic karyotyping and requires only shallow sequencing, making noninvasive prenatal screening cost-effective...

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...