‘<i>COV’COP</i>’ allows to detect CNVs responsible for inherited diseases among amplicons sequencing data

Derouault, Paco; Parfait, Béatrice; Moulinas, Rémi; Barrot, Claire-Cécile; Sturtz, Franck; Mérillou, Stéphane; Lia, Anne-Sophia

doi:10.1093/bioinformatics/btx017

Cited by 15 publications

(12 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sequencing data were processed using Torrent Suite Software v3.6 (Ion Torrent; Thermo Fisher Scientific, Inc) and compared to NextGENe independent analysis (Softgenetics) to align reads to the HG19 reference genome. Copy number variants (CNVs) were detected using the ‘COV’COP’ tool . All reported variants described using the HGVS nomenclature were attested to in HGMD and ClinVar combined with a literature search.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Multinodular goitre is a gateway for molecular testing of DICER1 syndrome

Oliver‐Petit¹,

Bertozzi

Grunenwald

et al. 2019

Clinical Endocrinology

View full text Add to dashboard Cite

Background DICER1 syndrome is an autosomal dominant disorder that predisposes individuals to develop benign or malignant tumours from infancy to adulthood. There is low‐to‐moderate penetrance of tumour development, which is sex‐ and age‐dependent. Multinodular goitre (MNG) is among the most highly penetrant phenotype of the disorder, especially in females. Patients and Methods We report a series of eight families referred for childhood‐onset of MNG or DICER1‐related tumours with familial history of MNG in relatives. No additional families with these criteria stated were identified during the same date. We screened DNA samples from the probands and members of their family (40) for constitutional DICER1 variants using Next Generation Sequencing tools. Results Germline pathogenic DICER1 gene variants were identified in all probands and several of their relatives: 64% presented with MNG/thyroidectomy as the phenotypic expression of the syndrome. DICER1 gene variants were identified in the RNAseIII and the PAZ domains. All tumour tissues studied presented clonal pathogenic variants in hotspot regions. Early identification of DICER1 variant carriers has permitted diagnosis and therapeutic scheme correction for two patients and cascade testing in relatives. Conclusions Multinodular goitre is uncommon in children. Childhood‐onset MNG, multiple occurrences of the disease within the same family, or its association with rare benign or malignant tumours should raise suspicions of anomalies in the DICER1 gene, as proposed by recent international recommendations. Early detection of DICER1 pathogenic variants has important consequences in terms of therapeutic strategy, early tumour screening, and genetic counselling.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Copy number variants (CNVs) were detected using the 'COV'COP' tool. 8 All reported variants described using the HGVS nomenclature were attested to in HGMD and ClinVar combined with a literature search.…”

Section: Dna Extraction and Sequencingmentioning

confidence: 99%

Multinodular goitre is a gateway for molecular testing of DICER1 syndrome

Oliver‐Petit¹,

Bertozzi

Grunenwald

et al. 2019

Clinical Endocrinology

View full text Add to dashboard Cite

show abstract

“…Z-score-based CNV detection: "Z-detection". From the raw read count of each amplicon, CovCopCan applies the same corrections and normalization as the Cov'Cop tool [11], resulting in a normalized read count value (NRC) for each amplicon (see S1 File). Starting from this point, we developed a new CNV-detection algorithm, based on the z-score.…”

Section: Cnv-detection Algorithmmentioning

confidence: 99%

“…Some of these tools require control samples to establish a reference set of data (ONCOCNV [7]). For others (ExomeDepth [8], IonCopy [9], DeviCNV [10], Cov'Cop [11]), control samples are not necessary. Indeed, if the CNV is rare, the other patient samples tested in the same run can serve as controls.…”

Section: Introductionmentioning

confidence: 99%

CovCopCan: An efficient tool to detect Copy Number Variation from amplicon sequencing data in inherited diseases and cancer

Derouault¹,

Chauzeix

Rizzo

et al. 2020

PLoS Comput Biol

View full text Add to dashboard Cite

Molecular diagnosis is an essential step of patient care. An increasing number of Copy Number Variations (CNVs) have been identified that are involved in inherited and somatic diseases. However, there are few existing tools to identify them among amplicon sequencing data generated by Next Generation Sequencing (NGS). We present here a new tool, CovCopCan, that allows the rapid and easy detection of CNVs in inherited diseases, as well as somatic data of patients with cancer, even with a low ratio of cancer cells to healthy cells. This tool could be very useful for molecular geneticists to rapidly identify CNVs in an interactive and user-friendly way. This is a PLOS Computational Biology Software paper.PLOS Computational Biology | https://doi.

show abstract

“…Sequenced libraries can be prepared by capture or by amplicons. Both methods are efficient for the detection of single-nucleotide variants or short indels, however only a few tools are available for the detection of large deletions or duplications, especially with amplicon sequencing data, such as Cov’Cop and CovCopCan [7] , [8] . Molecular diagnosis being an essential step of patient care, we believe it is crucial to improve the detection of SVs to increase the rate of positive diagnosis by using several bioinformatics approaches to analyze NGS data.…”

Section: Introductionmentioning

confidence: 99%

A mutation can hide another one: Think Structural Variants!

Miressi¹,

Faye²,

Pyromali³

et al. 2020

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

Next Generation Sequencing (NGS) using capture or amplicons strategies allows the detection of a large number of mutations increasing the rate of positive diagnosis for the patients. However, most of the detected mutations are Single Nucleotide Variants (SNVs) or small indels. Structural Variants (SVs) are often underdiagnosed in inherited genetic diseases, probably because few user-friendly tools are available for biologists or geneticists to identify them easily. We present here the diagnosis of two brothers presenting a demyelinating motor-sensitive neuropathy: a presumed homozygous c.5744_5745delAT in exon 10 of SACS gene was initially detected, while actually these patients were heterozygous for this mutation and harbored a large deletion of SACS exon 10 in the other allele. This hidden mutation has been detected thanks to the user-friendly CovCopCan software. We recommend to systematically use such a software to screen NGS data in order to detect SVs, such as Copy Number Variations, to improve diagnosis of the patients.

show abstract

‘COV’COP’ allows to detect CNVs responsible for inherited diseases among amplicons sequencing data

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 15 publications

References 2 publications

Multinodular goitre is a gateway for molecular testing of DICER1 syndrome

Multinodular goitre is a gateway for molecular testing of DICER1 syndrome

CovCopCan: An efficient tool to detect Copy Number Variation from amplicon sequencing data in inherited diseases and cancer

A mutation can hide another one: Think Structural Variants!

Contact Info

Product

Resources

About