Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 65,094 bioRxiv papers from 288,491 authors.

Linked-Read sequencing resolves complex structural variants

By Sarah Garcia, Stephen Williams, Andrew Wei Xu, Jill Herschleb, Patrick Marks, David Stafford, Deanna M Church

Posted 08 Dec 2017
bioRxiv DOI: 10.1101/231662

Large genomic structural variants (>50bp) are important contributors to disease, yet they remain one of the most difficult types of variation to accurately ascertain, in part because they tend to cluster in duplicated and repetitive regions, but also because the various signals for these events can be challenging to detect with short reads. Clinically, aCGH and karyotype remain the most commonly used assays for genome-wide structural variant (SV) detection, though there is clear potential benefit to an NGS-based assay that accurately detects both SVs and single nucleotide variants. Linked-Read sequencing is a relatively simple, fast, and cost-effective method that is applicable to both genome and targeted assays. Linked-Reads are generated by performing haplotype-level dilution of long input DNA molecules into >1 million barcoded partitions, generating barcoded short reads within those partitions, and then performing short read sequencing in bulk. We performed 30x Linked-Read genome sequencing on a set of 23 samples with known balanced or unbalanced SVs. Twenty-seven of the 29 known events were detected and another event was called as a candidate. Sequence downsampling was performed on a subset to determine the lowest sequence depth required to detect variations. Copy-number variants can be called with as little as 1-2x sequencing depth (5-10Gb) while balanced events require on the order of 10x coverage for variant calls to be made, although specific signal is clearly present at 1-2x sequencing depth. In addition to detecting a full spectrum of variant types with a single test, Linked-Read sequencing provides base-level resolution of breakpoints, enabling complete resolution of even the most complex chromosomal rearrangements.

Download data

  • Downloaded 1,534 times
  • Download rankings, all-time:
    • Site-wide: 3,654 out of 65,094
    • In genomics: 682 out of 4,449
  • Year to date:
    • Site-wide: 11,819 out of 65,094
  • Since beginning of last month:
    • Site-wide: 12,595 out of 65,094

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News