Haplotyping-Assisted Diploid Assembly and Variant Detection with Linked Reads

Yunfei Hu, Chao Yang, Lu Zhang*, Xin Zhou*

*Corresponding author for this work

Research output: Chapter in book/report/conference proceedingChapterpeer-review


Phasing is essential for determining the origins of each set of alleles in the whole-genome sequencing data of individuals. As such, it provides essential information for the causes of hereditary diseases and the sources of individual variability. Recent technical breakthroughs in linked-read (referred to as co-barcoding in other chapters of the book) and long-read sequencing and downstream analysis have brought the goal of accurate and complete phasing within reach. Here we review recent progress related to the assembly and phasing of personal genomes based on linked-reads and related applications. Motivated by current limitations in generating high-quality diploid assemblies and detecting variants, a new suite of software tools, Aquila, was developed to fully take advantage of linked-read sequencing technology. The overarching goal of Aquila is to exploit the strengths of linked-read technology including long-range connectivity and inherent phasing of variants for reference-assisted local de novo assembly at the whole-genome scale. The diploid nature of the assemblies facilitates detection and phasing of genetic variation, including single nucleotide variations (SNVs), small insertions and deletions (indels), and structural variants (SVs). An extension of Aquila, Aquila_stLFR, focuses on another newly developed linked-reads sequencing technology, single-tube long-fragment read (stLFR). AquilaSV, a region-based diploid assembly approach, is used to characterize structural variants and can achieve diploid assembly in one target region at a time. Lastly, we introduce HAPDeNovo, a program that exploits phasing information from linked-read sequencing to improve detection of de novo mutations. Use of these tools is expected to harness the advantages of linked-reads technology, improve phasing, and advance variant discovery.

Original languageEnglish
Title of host publicationHaplotyping
Subtitle of host publicationMethods and Protocols
EditorsBrock A. Peters, Radoje Drmanac
PublisherHumana Press Inc.
Number of pages22
ISBN (Electronic)9781071628195
ISBN (Print)9781071628188, 9781071628218
Publication statusPublished - 7 Nov 2022

Publication series

NameMethods in Molecular Biology
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Scopus Subject Areas

  • Molecular Biology
  • Genetics

User-Defined Keywords

  • Aquila
  • Diploid assembly
  • Haplotype estimation
  • Linked-read sequencing
  • Structural variants
  • Variant phasing


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