HaploClique

HaploClique reconstructs viral quasispecies from next-generation sequencing (NGS) data to resolve intra-host haplotypes for analyses of diversity, evolution, and treatment-relevant variants.

Key Features:

• Statistical Modeling for Paired-End Reads: Employs a statistical model tailored to paired-end reads that accounts for mutations, insertions, and deletions.
• Iterative Maximal Clique Enumeration: Uses iterative maximal clique enumeration to assemble read pairs into progressively longer haplotypes for global haplotype assembly.
• Performance and Accuracy: Demonstrates superior performance compared to existing haplotype inference methods, enabling reconstruction of error-free full-length haplotypes from low-coverage samples and detection of large insertions and deletions at low frequencies.
• Clinical Validation on HCV: Validated on clinical hepatitis C virus (HCV) sequencing data, identifying a novel deletion of 357±167 bp that was confirmed by independent long-read sequencing.

Scientific Applications:

• Viral Evolution and Pathogenesis: Reconstructs quasispecies structure to study viral evolution, adaptation mechanisms, and pathogenicity.
• Treatment Outcomes: Characterizes intra-host genetic diversity to inform treatment strategies and predict resistance to antiviral therapies.
• Genetic Diversity Analysis: Provides a framework for analyzing intra-host viral diversity in studies of disease progression and epidemiology.

Methodology:

Uses a statistical model for paired-end reads that accounts for mutations, insertions, and deletions combined with an iterative maximal clique enumeration procedure that assembles read pairs into progressively longer haplotypes for global quasispecies reconstruction.