ABSTRACT

In this chapter, the authors discusses the modeling strategy behind Topological Associating Domainbit (TADbit), a computational tool developed in their group, which is designed with the aim of providing a single tool for the complete analysis and three-dimensional (3D) modeling of Chromosome Conformation Capture (3C)-based experiments. One of the crucial steps in the TADbit modeling approach is converting the 3C interaction frequencies into harmonic distance restraints. Since the very first introduction of the 3C-based technologies, they have been complemented by computational techniques that take as input the measured interaction frequencies to determine the structural folding of genomes and genomic domains. The values of the free TADbit parameters to be used for modeling the genomic domain under investigation are determined by a systematic grid search exploring several of the possible combinations. The modeling strategy starts by describing each bin of the 3C interaction matrix as a spherical particle of a given radius.