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Adapting a well-established formalism of ideal polymer network in polymer physics,we develop a method to infer three-dimensional(3D)folding of chromatin from Hi-C data.The 3D chromosome structures generated from our proposal,termed the heterogeneous loop model(HLM),visualize chromosome organizations that can substantiate the measurements from FISH,ChIA-PET,and RNA-Seq signals.We demonstrate the utility of HLM with a few case studies.Specifically,the HLM-generated chromosome structures not only reproduce the spatial distribution of topologically associated domains(TADs)from FISH measurement but also show the phase-segregated conformations of A-and B-type TADs explicitly.The chromatin globules of α-globin gene domain modeled by HLM for two distinct cell lines are employed to explain why gene expression levels in the two cell lines differ from each other.Finally,HLM-generated chromosome 19 of mouse embryonic stem cells(mESCs)using single-cell Hi-C data collected over each cell cycle phase offers dramatic view of changes in chromosome conformations along the cell cycle.HLM can be used as a computationally efficient and versatile modeling tool to generate chromosome structures with which to decipher the structural origin of genome function.