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HiVA (Haplarithm inference of Variant Alleles) is an interactive web platform for genome haplarithmisis of DNA samples derived from a large number of cells down to a single cell. HiVA automatically reconstructs parental haplarithms (i.e. haplarithm profiles indicating both haplotypes and copy number states) and provides a user-friendly interface for scrutinizing allelic imbalances across the genome. HiVA is unique as it can uncover mechanistic/segregational origin of genomic aberrations. As such, HiVA can discern meiotic and mitotic origin of aberrations and has the capacity of identifying mosaicisms, chimaerisms, dispermic fertilizations, diplospermies, polarbody fusions, parthenogenetic/gynogenetic and androgenetic genomes, hydatidiform moles, etc. These features therefore would allow scrutinizing the aetiology of genetic disorders.

HiVA is an ensemble of different computational and visualization modules and is currently available for Academic Use Only. HiVA is backed by two patent applications (‪ WO2015028576 ‬ and WO2011157846 ‪ ‬).

The Principles of Haplarithmisis

Haplarithmisis applies the following steps:

The parental genotypes are phased via an available SNP genotype derived from a close relative (see analysis options of haplarithmsis).
The informative SNP loci are identified. A SNP locus is defined informative when one parent is heterozygous and the other parent is homozygous for this SNP.
The informative SNPs are categorized as paternal or maternal. An informative SNP is defined ‘‘paternal’’ when the father’s genotype is heterozygous and the mother’s genotype is homozygous. Similarly, an informative SNP is defined ‘‘maternal’’ when the mother’s SNP genotype is heterozygous and the father’s SNP genotype is homozygous.
These maternal and paternal informative SNP loci are subcategorized on the basis of phased parental SNP genotype combinations.
The SNP BAF values of the DNA sample are distributed into a paternal or maternal category according to the informative parental SNP genotypes defined in step 3, and further into four parental subcategories (P1, P2, M1, M2) according to the informative phased parental SNP genotypes defined in step 4.
The BAF values are subsequently mirrored around the 0.5 axis for those SNPs where either parent has a heterozygous SNP call BA after phasing.
Per subcategory (P1, P2, M1, M2), these BAF values for consecutive SNPs in the genome are segmented, emerging homologous recombination between the parental H1 and H2.
These segments and the underlying processed SNP BAF values are eventually visualized into two separate haplarithmisis profiles, i.e. ‘‘haplarithms’’.