scholarly journals panelcn.MOPS: Copy-number detection in targeted NGS panel data for clinical diagnostics

2017 ◽  
Vol 38 (7) ◽  
pp. 889-897 ◽  
Author(s):  
Gundula Povysil ◽  
Antigoni Tzika ◽  
Julia Vogt ◽  
Verena Haunschmid ◽  
Ludwine Messiaen ◽  
...  
Keyword(s):  
Panel Data ◽  
Copy Number ◽  
Clinical Diagnostics ◽  
Targeted Ngs ◽  
Copy Number Detection

scholarly journals Accurate clinical detection of exon copy number variants in a targeted NGS panel using DECoN

2016 ◽  
Vol 1 ◽  
pp. 20 ◽  
Author(s):  
Anna Fowler ◽  
Shazia Mahamdallie ◽  
Elise Ruark ◽  
Sheila Seal ◽  
Emma Ramsay ◽  
...  
Keyword(s):  
False Discovery Rate ◽  
Sensitivity And Specificity ◽  
Copy Number ◽  
Clinical Laboratory ◽  
Copy Number Variants ◽  
High Sensitivity ◽  
Targeted Next Generation Sequencing ◽  
Gene Testing ◽  
False Discovery ◽  
Targeted Ngs

Background: Targeted next generation sequencing (NGS) panels are increasingly being used in clinical genomics to increase capacity, throughput and affordability of gene testing. Identifying whole exon deletions or duplications (termed exon copy number variants, ‘exon CNVs’) in exon-targeted NGS panels has proved challenging, particularly for single exon CNVs.  Methods: We developed a tool for the Detection of Exon Copy Number variants (DECoN), which is optimised for analysis of exon-targeted NGS panels in clinical settings. We evaluated DECoN performance using 96 samples with independently validated exon CNV data. We performed simulations to evaluate DECoN detection performance of single exon CNVs and evaluate performance using different coverage levels and sample numbers. Finally, we implemented DECoN in a clinical laboratory that tests BRCA1 and BRCA2 with the TruSight Cancer Panel (TSCP). We used DECoN to analyse 1,919 samples, validating exon CNV detections by multiplex ligation-dependent probe amplification (MLPA).  Results: In the evaluation set, DECoN achieved 100% sensitivity and 99% specificity for BRCA exon CNVs, including identification of 8 single exon CNVs. DECoN also identified 14/15 exon CNVs in 8 other genes. Simulations of all possible BRCA single exon CNVs gave a mean sensitivity of 98% for deletions and 95% for duplications. DECoN performance remained excellent with different levels of coverage and sample numbers; sensitivity and specificity was >98% with the typical NGS run parameters. In the clinical pipeline, DECoN automatically analyses pools of 48 samples at a time, taking 24 minutes per pool, on average. DECoN detected 24 BRCA exon CNVs, of which 23 were confirmed by MLPA, giving a false discovery rate of 4%. Specificity was 99.7%.  Conclusions: DECoN is a fast, accurate, exon CNV detection tool readily implementable in research and clinical NGS pipelines. It has high sensitivity and specificity and acceptable false discovery rate. DECoN is freely available at www.icr.ac.uk/decon.

scholarly journals Comparative analysis of copy number detection by whole-genome BAC and oligonucleotide array CGH

2010 ◽  
Vol 3 (1) ◽  
pp. 11 ◽  
Author(s):  
Nicholas J Neill ◽  
Beth S Torchia ◽  
Bassem A Bejjani ◽  
Lisa G Shaffer ◽  
Blake C Ballif
Keyword(s):  
Comparative Analysis ◽  
Copy Number ◽  
Array Cgh ◽  
Oligonucleotide Array ◽  
Whole Genome ◽  
Copy Number Detection

Accurate and precise targeted NGS with BRCA MASTR Plus Dx for BRCA1 and BRCA2 mutation detection in formalin-fixed paraffin-embedded tumor tissue-derived DNA.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23116-e23116
Author(s):  
Gaelle Boulet ◽  
Djana Van Barel ◽  
Annelies Rotthier ◽  
Dirk Goossens ◽  
Jurgen Del-Favero
Keyword(s):  
Multicentre Study ◽  
Tumor Tissue ◽  
Clinical Diagnostics ◽  
Clinical Samples ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Formalin Fixed Paraffin ◽  
Targeted Ngs ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

e23116 Background: Targeted next-generation sequencing (NGS) has tremendous potential in clinical diagnostics as it allows oncogenetic profiling to steer therapy. Inhibitors of poly-(ADP-ribose) polymerase (PARPi) have emerged as a new class of targeted anti-cancer drugs, specifically for tumors showing homologous recombination repair deficiency, including BRCA1- and BRCA2-mutated ovarian and breast cancers. This multicentre study evaluated the performance of BRCA Tumor MASTR Plus Dx* (Multiplicom) to routinely diagnose somatic and germline BRCA mutations in formalin-fixed paraffin-embedded (FFPE) tumor tissue-derived DNA. Methods: Three genetic centres participated in this performance evaluation study (PES) to detect single nucleotide variants (SNV) and small indels in the BRCA genes at a variant allele frequency down to 5%. The sample population comprised 54 FFPE-derived DNA extracts from 51 clinical and 3 reference samples. DNA extracts were subjected to quality control using Multiplicom’s QC plex assay. The clinical samples were characterized using an independent targeted NGS method and Integrative Genomics Viewer (IGV) analysis of the mapped raw reads. SNV calling was performed using third-party bioinformatics platforms in the BRCA coding regions +/- 2 intronic bp. Results: BRCA MASTR Plus Dx*showed a uniformity of 93.9%, i.e. the percentage of amplicons with at least 0.2x the mean amplicon coverage, and a target specificity of 99.1%. The limit of detection (LOD) proved to be as low as 1%. The diagnostic accuracy was ≥ 99.99% [95% CI ≥ 99.98%] (100% sensitivity [95% CI ≥ 99.02%] and ≥ 99.99% specificity [95% CI ≥ 99.98%]). Both repeatability and reproducibility were ≥ 99.99% [95% CI ≥ 99.98%]. Lot equivalence was 100% [95% CI ≥ 99.99%]. Conclusions: This multicentre study demonstrated that BRCA MASTR Plus Dx* can be routinely applied as an accurate and precise method with an LOD of 1%. The assay can be used to direct patients with somatic or germline BRCA mutations to PARPi therapy. Currently, a PES for BRCA MASTR Plus Dx* and Multiplicom’s MASTR Reporter software is ongoing. *Products described above are CE-IVD and not available for sale in the US

scholarly journals CNV Workshop: an integrated platform for high-throughput copy number variation discovery and clinical diagnostics

2010 ◽  
Vol 11 (1) ◽  
pp. 74 ◽  
Author(s):  
Xiaowu Gai ◽  
Juan C Perin ◽  
Kevin Murphy ◽  
Ryan O'Hara ◽  
Monica D'arcy ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
High Throughput ◽  
Copy Number ◽  
Clinical Diagnostics ◽  
Integrated Platform ◽  
Number Variation

scholarly journals Counting Chromosomes to Exons: Advances in Copy Number Detection

2013 ◽  
Vol 1 (2) ◽  
pp. 71-80 ◽  
Author(s):  
Swaroop Aradhya ◽  
Athena M. Cherry ◽  
Santhosh Girirajan
Keyword(s):  
Copy Number ◽  
Copy Number Detection

The clinical context of copy number variation in the human genome

2010 ◽  
Vol 12 ◽  
Author(s):  
Charles Lee ◽  
Stephen W. Scherer
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Clinical Diagnostics ◽  
Genomic Variation ◽  
Single Nucleotide ◽  
Genomic Changes ◽  
Creative Solutions ◽  
Number Variation ◽  
The Relationship ◽  
Prevalent Form

During the past five years, copy number variation (CNV) has emerged as a highly prevalent form of genomic variation, bridging the interval between long-recognised microscopic chromosomal alterations and single-nucleotide changes. These genomic segmental differences among humans reflect the dynamic nature of genomes, and account for both normal variations among us and variations that predispose to conditions of medical consequence. Here, we place CNVs into their historical and medical contexts, focusing on how these variations can be recognised, documented, characterised and interpreted in clinical diagnostics. We also discuss how they can cause disease or influence adaptation to an environment. Various clinical exemplars are drawn out to illustrate salient characteristics and residual enigmas of CNVs, particularly the complexity of the data and information associated with CNVs relative to that of single-nucleotide variation. The potential is immense for CNVs to explain and predict disorders and traits that have long resisted understanding. However, creative solutions are needed to manage the sudden and overwhelming burden of expectation for laboratories and clinicians to assay and interpret these complex genomic variations as awareness permeates medical practice. Challenges remain for understanding the relationship between genomic changes and the phenotypes that might be predicted and prevented by such knowledge.

Copy Number Detection in Exome Sequencing Compared to Chromosomal Microarray in a Clinical Setting

2016 ◽  
Vol 209 (6) ◽  
pp. 300
Author(s):  
Ramakrishnan Rajagopalan ◽  
Batsal Devkota ◽  
Vijayakumar Jayaraman ◽  
Sawona Biswas ◽  
Nancy B. Spinner ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Clinical Setting ◽  
Copy Number ◽  
Chromosomal Microarray ◽  
Copy Number Detection

scholarly journals Copy number variation analysis and targeted NGS in 77 families with suspected Lynch syndrome reveals novel potential causative genes

2018 ◽  
Vol 143 (11) ◽  
pp. 2800-2813 ◽  
Author(s):  
Katrin Kayser ◽  
Franziska Degenhardt ◽  
Stefanie Holzapfel ◽  
Sukanya Horpaopan ◽  
Sophia Peters ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Copy Number Variation ◽  
Copy Number ◽  
Variation Analysis ◽  
Copy Number Variation Analysis ◽  
Targeted Ngs ◽  
Number Variation

Abstract 5119: Customizable all-in-one cancer panels to detect copy number variation, DNA rearrangement and mutations by targeted NGS

2019 ◽  
Author(s):  
Arjun Vadapalli ◽  
Ashutosh Ashutosh ◽  
Heather Tao ◽  
Linus Forsmark ◽  
Christian Le Cocq ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Dna Rearrangement ◽  
Targeted Ngs ◽  
Number Variation ◽  
Cancer Panels
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