Haplotyping-Assisted Diploid Assembly and Variant Detection with Linked Reads

Area of Science:

• Genomics
• Bioinformatics
• Molecular Biology

Background:

• Phasing, determining allele origins in whole-genome sequencing, is crucial for understanding hereditary diseases and individual variability.
• Recent advances in linked-read and long-read sequencing technologies have significantly improved the potential for accurate and complete genome phasing.
• Current limitations exist in generating high-quality diploid assemblies and detecting genetic variants comprehensively.

Approach:

• Review of recent progress in personal genome assembly and phasing using linked-read technologies.
• Development of the Aquila software suite, designed to leverage linked-read sequencing for reference-assisted local de novo assembly.
• Introduction of Aquila_stLFR for single-tube long-fragment read technology, AquilaSV for region-based diploid assembly of structural variants, and HAPDeNovo for improved de novo mutation detection.

Key Points:

• Aquila software exploits linked-read strengths for long-range connectivity and inherent variant phasing.
• Diploid assemblies generated by Aquila facilitate the detection and phasing of single nucleotide variations (SNVs), insertions/deletions (indels), and structural variants (SVs).
• Specialized tools like Aquila_stLFR, AquilaSV, and HAPDeNovo address specific challenges in linked-read sequencing applications.

Conclusions:

• The reviewed tools harness linked-read technology to enhance genome phasing accuracy and completeness.
• Improved phasing and variant discovery advance the understanding of genetic variation and its role in health and disease.
• These advancements are expected to significantly contribute to personal genomics and the study of genetic disorders.