3DChromoTwist: An Interactive Gamified Framework for Exploring Hi-C derived 3D Chromosome Structures

Reconstructing the three-dimensional (3D) structure of chromosomes provides important insights into spatial genome
organization and its relationships with biological processes such as gene regulation and DNA replication. Hi-C generates
interaction frequency matrices that quantify contacts between genomic loci. However, relating two-dimensional Hi-C
interaction patterns to three-dimensional chromosome organization can be difficult to interpret, particularly for beginners
and non-specialists. Interactive manipulation and gamification of 3D genome structures provides a way to make these
abstract spatial relationships easier to explore and understand. We present 3DChromoTwist, a web-based gamified
framework for interactive exploration of Hi-C-derived 3D genome structure reconstruction. The platform provides a
Hi-C-derived 3D chromosome structure as the reconstruction target, together with an initial configuration of genomic
loci that users can manipulate during gameplay. Users move genomic loci and receive feedback as their structure
becomes closer to the target, allowing them to directly explore how chromosome interaction patterns relate to 3D
genome organization. 3DChromoTwist also captures structured gameplay trajectories for future analysis of human-
guided reconstruction strategies and AI-assisted approaches to 3D genome modeling. 3DChromoTwist is available
at https://bioaiweb.eng.unt.edu/3dchromotwist, with an option for voluntary participation in a University of North
Texas–approved research study.