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Review
. 2019 Nov 20;20(1):246.
doi: 10.1186/s13059-019-1828-7.

Structural variant calling: the long and the short of it

Medhat Mahmoud  1 , Nastassia Gobet  2   3 , Diana Ivette Cruz-Dávalos  3   4 , Ninon Mounier  3   5 , Christophe Dessimoz  6   7   8   9   10 , Fritz J Sedlazeck  11
Affiliations
Review

Structural variant calling: the long and the short of it

Medhat Mahmoud et al. Genome Biol. .

Abstract

Recent research into structural variants (SVs) has established their importance to medicine and molecular biology, elucidating their role in various diseases, regulation of gene expression, ethnic diversity, and large-scale chromosome evolution-giving rise to the differences within populations and among species. Nevertheless, characterizing SVs and determining the optimal approach for a given experimental design remains a computational and scientific challenge. Multiple approaches have emerged to target various SV classes, zygosities, and size ranges. Here, we review these approaches with respect to their ability to infer SVs across the full spectrum of large, complex variations and present computational methods for each approach.

Keywords: De novo assembly; Gene fusion; Hybrid; Long-read; Mapping; RNA-Seq; Short-read; Structural variant (SV) detection.

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Conflict of interest statement

FJS obtained a Pacbio SMRT grant in 2018 and had multiple travels sponsored by Pacific Biosciences, Inc. and Oxford Nanopore Technologies Ltd. CD has been providing consulting services for Pacific Biosciences, Inc. All other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Comparison between de novo assembly, short-read and long-read mapping approaches to identify structural variants. For de novo assembly approaches, the relative positions of the segments in the dot plot indicate the type and size of the SV. For short-read-based mapping approaches, paired-end (red) and split reads (purple) are typically used to decipher the type size and location. In addition, the coverage can be used to improve the detection of deletions and duplications. Long-read-based mapping approaches typically leverage the alignment patterns of long reads (green) to detect the different types of SVs
Fig. 2
Fig. 2
Qualitative overview of structural variant calling methodology using short reads and long reads and their associated costs. a, A qualitative comparison of the different SV methodologies ranging across technologies (whole genome and RNA-Seq using short and long reads) to different approaches (mapping vs. assembly) with respect to their costs and recall. b, The ratio of improvement in the number of SVs detected from using long reads across four human and two non-human studies. Overall, each study shows a clear improvement of using the longer reads. Additional file 1: Table S1 shows the details of each study
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