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GAMIBHEAR: whole-genome haplotype reconstruction from genome architecture mapping data

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Item Type:Preprint
Title:GAMIBHEAR: whole-genome haplotype reconstruction from genome architecture mapping data
Creators Name:Markowski, J. and Kempfer, R. and Kukalev, A. and Irastorza-Azcarate, I. and Loof, G. and Pombo, A. and Schwarz, R.F.
Abstract:Motivation: Understanding haplotype-specific regulatory mechanisms becomes increasingly important in genomics and medical research. Investigating differences in allele-specific gene expression, epigenetic changes and their causal variants greatly benefits from haplotype reconstruction or phasing of genetic variants, but direct evidence for the haplotype structure is difficult to obtain from standard short-read sequencing data. Chromatin conformation data obtained from 3C experiments allows inference of haplotypes because inter-chromosomal contacts are more frequent than homologous intra-chromosomal contacts, but these data suffer from technical biases owing to the digestion and ligation process of the 3C technique. Genome Architecture Mapping (GAM) is a novel digestion- and ligation-free method for the inference of chromatin conformation from nuclear cryosections. Due to its high resolution and independence of enzymatic digestion it is well-suited for haplotype reconstruction and for detecting haplotype-specific chromatin contacts. Results: Here, we present GAMIBHEAR, a tool for accurate haplotype reconstruction from GAM data. GAMIBHEAR aggregates allelic co-observation frequencies across multiple nuclear slices and employs a GAM-specific probabilistic model of haplotype capture to optimise 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 GAM data and the accuracy of GAMIBHEAR to infer genome-wide haplotypes. Availability: GAMIBHEAR is available as an R package under the open source GPL-2 license at https://bitbucket.org/schwarzlab/gamibhear Maintainer: julia.markowski{at}mdc-berlin.de
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.01.30.927061
Date:31 January 2020
Official Publication:https://doi.org/10.1101/2020.01.30.927061
Related to:
https://edoc.mdc-berlin.de/20168/Final version

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