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GPSeq generates growing rings of digestion, as confirmed by super-resolution microscopy (STED). Here, we aim at estimating a genomic region's nuclear 3D position (relative to the nuclear center/lamina) through the combined analysis of sequencing data coming from multiple GPSeq conditions.

Introduction

The GPSeq technique uses a restriction enzyme to cut, with different probability, peripheral and central loci in fixed nuclei. The restricted sites are then ligated to a linker, compatible with both imaging and sequencing.

Imaging is generally used as a validation step, to verify that restriction was properly performed and that growing rings of digestion were generated (confirmed by STED). On the other hand, information on the restricted regions sequence can is obtained through sequencing.

Usually, a GPSeq experiment consists of a series of conditions in which the restriction happens with increasing probability towards the nuclear center. Thus, a non-trivial challenge is to estimate the radial position of a genomic locus or region in a nucleus.