Computational methods for predicting 3D genomic organization from high-resolution chromosome conformation capture data

The advent of high-resolution chromosome conformation capture assays (such as 5C, Hi-C and Pore-C) has allowed for unprecedented sequence-level investigations into the structure-function relationship of the genome. In order to comprehensively understand this relationship, computational tools are required that utilize data generated from these assays to predict 3D genome organization (the 3D genome reconstruction problem). Many computational tools have been developed that answer this need, but a comprehensive comparison of their underlying algorithmic approaches has not been conducted. This manuscript provides a comprehensive review of the existing computational tools (from November 2006 to September 2019, inclusive) that can be used to predict 3D genome organizations from high-resolution chromosome conformation capture data. Overall, existing tools were found to use a relatively small set of algorithms from one or more of the following categories: dimensionality reduction, graph/network theory, maximum likelihood estimation (MLE) and statistical modeling. Solutions in each category are far from maturity, and the breadth and depth of various algorithmic categories have not been fully explored. While the tools for predicting 3D structure for a genomic region or single chromosome are diverse, there is a general lack of algorithmic diversity among computational tools for predicting the complete 3D genome organization from high-resolution chromosome conformation capture data.