Free-access copy-number variant detection tools for targeted next-generation sequencing data

Roca, Iria; González-Castro, Lorena; Fernández, Helena; Couce, María L.; Fernández–Marmiesse, Ana

doi:10.1016/j.mrrev.2019.02.005

Cited by 56 publications

(55 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, the role of CNVs in local adaptation relative to SNPs in non-model species is poorly understood and remains mostly restricted to a very limited number of animal and plant species in terrestrial environments (Tigano et al, 2018;Rinker et al, 2019;Nelson et al, 2018, Prunier et al, 2019, making this issue still largely unexplored in marine species. CNVs are also rarely studied on a large subset of individuals due to financial and technical constraints because classical approaches to detect CNVs, such as paired-end mapping, split read, de novo assembly or depth of coverage, required a reference genome and whole-genome resequencing at deep coverage (Roca et al, 2019). However, recent technological and methodological improvements in sequences analyses hold promise to address such issues.…”

Section: Introductionmentioning

confidence: 99%

Copy number variants outperform SNPs to reveal genotype-temperature association in a marine species

Dorant

Cayuela

Wellband

et al. 2020

Preprint

View full text Add to dashboard Cite

Copy number variants (CNVs) are a major component of genotypic and phenotypic variation in genomes. Yet, our knowledge on genotypic variation and evolution is often limited to single nucleotide polymorphism (SNPs) and the role of CNVs has been overlooked in non-model species, partly due to their challenging identification until recently. Here, we document the usefulness of reducedrepresentation sequencing data (RAD-seq) to detect and investigate copy number variants (CNVs) alongside SNPs in American lobster (Homarus americanus) populations. We conducted a comparative study to examine the potential role of SNPs and CNVs in local adaptation by sequencing 1141 lobsters from 21 sampling sites within the southern Gulf of St. Lawrence which experiences the highest yearly thermal variance of the Canadian marine coastal waters. Our results demonstrated that CNVs accounts for higher genetic differentiation than SNP markers. Contrary to SNPs for which no association was found, genetic-environment association revealed that 48 CNV candidates were significantly associated with the annual variance of sea surface temperature, leading to the genetic clustering of sampling locations despite their geographic separation. Altogether, we provide a strong empirical case that CNVs putatively contribute to local adaptation in marine species and unveil stronger spatial signal than SNPs.Our study provides the means to study CNVs in non-model species and underlines the importance to consider structural variants alongside SNPs to enhance our understanding of ecological and evolutionary processes shaping adaptive population structure.

show abstract

Section: Introductionmentioning

confidence: 99%

Copy number variants outperform SNPs to reveal genotype-temperature association in a marine species

Dorant

Cayuela

Wellband

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…CNVs are estimated to cause approximately 10% of disorders, and they seem to be even more involved in neurological disorders than in many other disorder groups [104,105]. CNVs can be detected from various types of next generation sequencing (NGS) data, and numerous CNV detection algorithms have been developed during recent years [103,106]. Usually, different technical approaches are needed for WES and gene panel data compared to WGS data, since the former produce non-continuous sequencing data [107].…”

Section: The Identification Of Copy Number Variants From Hts Datamentioning

confidence: 99%

“…The CNV detection algorithms tend to have differing CNV detection accuracy and biases in detected CNV classes: therefore, utilizing more than one algorithm is generally recommended to achieve comprehensive CNV detection results [106,[109][110][111]. Kosugi and colleagues list CNV detection algorithms for WGS data with relatively best performances for each structural variation category, including CNVs [103].…”

Section: The Identification Of Copy Number Variants From Hts Datamentioning

confidence: 99%

“…Kosugi and colleagues list CNV detection algorithms for WGS data with relatively best performances for each structural variation category, including CNVs [103]. For now, studies with comparably comprehensive algorithm comparisons are not available for WES and gene panel sequencing data, but numerous studies of smaller scale have been published to aid in making the choice [105,106,109,110].…”

Section: The Identification Of Copy Number Variants From Hts Datamentioning

confidence: 99%

See 1 more Smart Citation

Is Gene-Size an Issue for the Diagnosis of Skeletal Muscle Disorders?

Savarese

Välipakka

Johari

et al. 2020

JND

View full text Add to dashboard Cite

Human genes have a variable length. Those having a coding sequence of extraordinary length and a high number of exons were almost impossible to sequence using the traditional Sanger-based gene-by-gene approach. High-throughput sequencing has partly overcome the size-related technical issues, enabling a straightforward, rapid and relatively inexpensive analysis of large genes. Several large genes (e.g. TTN, NEB, RYR1, DMD) are recognized as disease-causing in patients with skeletal muscle diseases. However, because of their sheer size, the clinical interpretation of variants in these genes is probably the most challenging aspect of the high-throughput genetic investigation in the field of skeletal muscle diseases. The main aim of this review is to discuss the technical and interpretative issues related to the diagnostic investigation of large genes and to reflect upon the current state of the art and the future advancements in the field.

show abstract

“…Other benchmarks of CNV calling tools on targeted NGS panel data have been published. However, they were performed by the authors of the tools and executed against a single dataset (Johansson et al, 2016;Fowler et al, 2016;Povysil et al, 2017;Kim et al, 2017;Chiang et al, 2019), or used mainly simulated data with a small number of validated CNVs (Roca et al, 2019). The aim of this work is to perform an independent benchmark of multiple CNV calling tools, optimizing and evaluating them against multiple datasets generated in diagnostics settings, to identify the most suitable tools to be used for genetic diagnostics (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Benchmark of tools for CNV detection from NGS panel data in a genetic diagnostics context

Moreno-Cabrera

Valle

Castellanos

et al. 2019

Preprint

View full text Add to dashboard Cite

Motivation:Although germline copy number variants (CNVs) are the genetic cause of multiple hereditary diseases, detecting them from targeted next-generation sequencing data (NGS) remains a challenge. Existing tools perform well for large CNVs but struggle with single and multi-exon alterations. The aim of this work is to evaluate CNV calling tools working on gene panel NGS data with CNVs up to single-exon resolution and their suitability as a screening step before orthogonal confirmation in genetic diagnostics strategies.Results: Five tools (DECoN, CoNVaDING, panelcn.MOPS, ExomeDepth and CODEX2) were tested against four genetic diagnostics datasets (495 samples, 231 CNVs), using the default and sensitivityoptimized parameters. Most tools were highly sensitive and specific, but the performance was datasetdependant. In our in-house datasets, DECoN and panelcn.MOPS with optimized parameters showed enough sensitivity to be used as screening methods in genetic diagnostics. Availability:Benchmarking-optimization code is freely available at https://github.com/TranslationalBioinformaticsIGTP/CNVbenchmarkeR.

show abstract

Free-access copy-number variant detection tools for targeted next-generation sequencing data

Cited by 56 publications

References 82 publications

Copy number variants outperform SNPs to reveal genotype-temperature association in a marine species

Copy number variants outperform SNPs to reveal genotype-temperature association in a marine species

Is Gene-Size an Issue for the Diagnosis of Skeletal Muscle Disorders?

Benchmark of tools for CNV detection from NGS panel data in a genetic diagnostics context

Contact Info

Product

Resources

About