No abstract

The genome architecture mapping (GAM) is a recently developed methodology that offers the co-segregation probability of two genomic segments from an ensemble of thinly sliced nuclear profiles, enabling to probe and decipher the 3D chromatin organization. The co-segregation probability from GAM, which typically probes the length scale associated with the genomic separation greater than 1 MB, is, however, not identical to the contact probability obtained in Hi-C, and its correlation with inter-locus distance measured with FISH is not so good as the contact probability. In this study, by using a polymer-based model of chromatins, we derive a theoretical expression of the co-segregation probability as well as that of the contact probability, and carry out quantitative analyses of how they differ from each other. The results from our study, validated with in-silico GAM analysis on 3D genome structures from FISH, suggest that to attain strong correlation with the inter-locus distance, a properly normalized version of co-segregation probability needs to be calculated based on a large number of nuclear slices (n>103).