GAMIBHEAR: whole-genome haplotype reconstruction from Genome Architecture Mapping data

• Published in: Bioinformatics (Oxford, England) Vol. 37; no. 19; pp. 3128 - 3135
• Main Authors: Markowski, Julia, Kempfer, Rieke, Kukalev, Alexander, Irastorza-Azcarate, Ibai, Loof, Gesa, Kehr, Birte, Pombo, Ana, Rahmann, Sven, Schwarz, Roland F
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 11-10-2021
• Subjects: Original Papers
• ISSN: 1367-4803; 1367-4811; 1367-4811
• DOI: 10.1093/bioinformatics/btab238

Abstract
Motivation
Genome Architecture Mapping (GAM) was recently introduced as a digestion- and ligation-free method to detect chromatin conformation. Orthogonal to existing approaches based on chromatin conformation capture (3C), GAM’s ability to capture both inter- and intra-chromosomal contacts from low amounts of input data makes it particularly well suited for allele-specific analyses in a clinical setting. Allele-specific analyses are powerful tools to investigate the effects of genetic variants on many cellular phenotypes including chromatin conformation, but require the haplotypes of the individuals under study to be known a priori. So far, however, no algorithm exists for haplotype reconstruction and phasing of genetic variants from GAM data, hindering the allele-specific analysis of chromatin contact points in non-model organisms or individuals with unknown haplotypes.
Results
We present GAMIBHEAR, a tool for accurate haplotype reconstruction from GAM data. GAMIBHEAR aggregates allelic co-observation frequencies from GAM data and employs a GAM-specific probabilistic model of haplotype capture to optimize phasing accuracy. Using a hybrid mouse embryonic stem cell line with known haplotype structure as a benchmark dataset, we assess correctness and completeness of the reconstructed haplotypes, and demonstrate the power of GAMIBHEAR to infer accurate genome-wide haplotypes from GAM data.
Availability and implementation
GAMIBHEAR is available as an R package under the open-source GPL-2 license at https://bitbucket.org/schwarzlab/gamibhear.
Supplementary information
Supplementary data are available at Bioinformatics online.