WHdenovo

WHdenovo performs haplotype-resolved de novo assembly of diploid genomes from related individuals by integrating Illumina short-read and Pacific Biosciences (PacBio) long-read sequencing data.

Key Features:

• Pedigree Sequence Graph Approach: Constructs a pedigree sequence graph that integrates Illumina short reads from related individuals to represent diploid sequence variation.
• Integrated short- and long-read data: Aligns PacBio long reads to the pedigree sequence graph to leverage long-read contiguity together with short-read accuracy.
• Cost-Effective Sequencing Coverage: Demonstrates chromosomal-scale phased assemblies using combined data with as little as 30× Illumina and 15× PacBio coverage per individual in a trio.
• Haplotype Resolution and Variant Phasing: Partitions aligned long reads into two haplotypes to produce phased assemblies and enables detection and phasing of variants within pedigrees.

Scientific Applications:

• Mendelian disease research: Enables identification and phasing of causal variants within trios for studies of heritable disorders.
• Population genomics: Provides chromosomal-scale phased assemblies suitable for haplotype-level analyses in population and evolutionary studies.
• Large-scale pedigree sequencing projects: Supports projects such as the Personal Genome Project, Vertebrate Genome Project (VGP), and Genome in a Bottle (GIAB) that require high-quality haplotype-resolved assemblies from related individuals.

Methodology:

Constructs a pedigree sequence graph from Illumina short reads, aligns PacBio long reads to the graph, and partitions aligned reads into two haplotypes to generate phased assemblies optimized for trios.