BLR

BLR performs comprehensive haplotype phasing and structural variant calling from linked-read sequencing data for genome-wide haplotype and structural-variant analysis.

Key Features:

• Multi-Technology Compatibility: Supports data integration from Double-Barrelled Sequencing (DBS), 10× Genomics, TELL-seq, and single-tube Long Fragment Read (stLFR) linked-read platforms.
• High Accuracy in Haplotype Phasing: Achieves low switch error rates (<0.2%), megabase-scale phasing on DBS linked-reads, and 98.6% concordance for protein-coding genes against the GIAB benchmark set (v4.2.1).
• Structural Variant Analysis: Identifies large structural variants with results that align to reference assemblies such as HPRC-HG002.
• Improved Phasing Continuity and Accuracy: Produces more continuous phasing with reduced switch errors compared to diploid assembly using PacBio HiFi reads, and integration of low-coverage long reads (~10×) further increases contiguity and reduces errors in tandem repeat regions.
• Performance Metrics: In comparative analyses versus Long Ranger on 10× Genomics data, increases phase block N50 while maintaining low switch-error rates, and generates phase blocks for TELL-seq and stLFR comparable to or greater than those reported in original studies while sustaining low error rates.

Scientific Applications:

• Haplotype analysis: Precise genome-wide haplotype phasing for coding and noncoding regions.
• Structural variant detection: Genome-wide identification and characterization of large structural variants and comparison to reference assemblies.
• Genetic diversity studies: Analysis of haplotype and structural-variant diversity across samples and populations.
• Disease association mapping: Phased genotypes and SV calls to support genotype–phenotype and association analyses.
• Evolutionary biology: Investigation of haplotype structure and structural variation in evolutionary contexts.

Methodology:

Implements a flexible Snakemake workflow that processes raw FASTQ files end-to-end, integrates linked-read barcodes from DBS, 10× Genomics, TELL-seq, and stLFR, optionally incorporates low-coverage long reads (~10×) to improve phasing, and benchmarks results against GIAB v4.2.1, HPRC-HG002, Long Ranger, and diploid assemblies using PacBio HiFi reads.