Computational Approaches for Understanding Sequence Variation Effects on the 3D Genome Architecture

Decoding how genomic sequence and its variations affect 3D genome architecture is indispensable for understanding the genetic architecture of various traits and diseases. The 3D genome organization can be significantly altered by genome variations and in turn impact the function of the genomic sequence. Techniques for measuring the 3D genome architecture across spatial scales have opened up new possibilities for understanding how the 3D genome depends upon the genomic sequence and how it can be altered by sequence variations. Computational methods have become instrumental in analyzing and modeling the sequence effects on 3D genome architecture, and recent development in deep learning sequence models have opened up new opportunities for studying the interplay between sequence variations and the 3D genome. In this review, we focus on computational approaches for both the detection and modeling of sequence variation effects on the 3D genome, and we discuss the opportunities presented by these approaches.