haplotyperesolved

Haplotyperesolved refers to genomes, assemblies, or datasets in which the two haplotypes of a diploid organism have been separated and reconstructed, allowing sequence, variants, and annotations to be assigned to the maternal or paternal chromosome. In practice, haplotyperesolved data support analyses that distinguish allele-specific effects and inheritance patterns.

Achieving haplotyperesolved genomes typically combines experimental design with computational phasing. Approaches include trio sequencing, in which parental genotypes guide phasing of the offspring, and long-read or ultra-long read sequencing that enables long-range haplotype blocks. Additional methods use chromosome conformation capture (Hi-C) data or Strand-seq to connect distant variants. Computational tools such as HapCUT2, WhatsHap, and SHAPEIT perform read-based or population-based phasing; assembly-based methods like trio-binning or haplotype-aware assemblers (for example, hifiasm) can produce phased genome assemblies.

Applications include accurate characterization of allele-specific expression, imprinting, compound heterozygosity, and disease-associated haplotypes; improved imputation and population genetics analyses; and the creation of reference-grade phased genomes for personalized medicine and evolutionary studies.

Challenges include incomplete phasing in repetitive regions, phasing accuracy across the genome, data requirements and cost, and handling structural variants. Ongoing developments aim to improve phasing speed, scalability, and the integration of diverse data types.

See also: haplotyping, genome assembly, phasing, trio-binning, haplotype-resolved assembly.