Inferring interphase chromosomal structure from multiplexed fluorescence <i>in situ</i> hybridization data: A unified picture from human and mouse cells

Abstract

We analyze multiplexed fluorescence in situ hybridization (m-FISH) data for human and mouse cell lines. The m-FISH technique uses fluorescently-labeled single-stranded probes which hybridize to specific chromosomal regions, thereby allowing the measurement of the spatial positions of up to ∼100 tagged sites for several thousands of interphase chromosomes. Our analysis focuses on a wide range of different cell lines and two distinct organisms and provides a unified picture of chromatin structure for scales ranging from 5 kb (kilobases) up to 2 Mb (megabases), thus covering a genomic region of almost three orders of magnitude. Confirming recent analysis [Remini et al., Phys. Rev. E 109, 024408 (2024)], we show that there are two characteristic arrangements of chromatin referred to as phase α (crumpled globule) and phase β (looped domain) and discuss the physical properties of these phases. We show that a simple heterogeneous random walk model captures the main behavior observed in experiments and brings considerable insights into chromosomal structure.