ABSTRACT

This chapter summarizes various experimental methods that are used in the 4DN joint analysis project to shed light on aspects of the genome structural organization. It provides an overview of data-driven computational methods that use experimental data to generate structural models consistent with it. The chapter discusses methods for comprehensive data integration, which can reveal the folded states of complete genomes, and consider the structural heterogeneity across different cells. Acquiring spatial information for a chromatin polymer containing billions of basepairs is a daunting task, especially when considering genome dynamics, which leads to structural variations from cell to cell in an isogenic sample. Various imaging technologies visualize the structural organization and dynamics of the nucleus at spatio-temporal resolution. Microscopy tools are important in providing direct spatial relationships of genomic loci and nuclear bodies. A caveat in the resampling procedure comes from the fact that ensemble datasets can include conflicting data from mutually exclusive chromatin conformations.