biostudies-literatureZheng YNHGRI NIH HHSnational institutes of health222https://www.ebi.ac.uk/biostudies/studies/S-EPMC9575231biostudies-literatureUnknown23(1)Single-cell high-throughput chromatin conformation capture methodologies (scHi-C) enable profiling of long-range genomic interactions. However, data from these technologies are prone to technical noise and biases that hinder downstream analysis. We develop a normalization approach, BandNorm, and a deep generative modeling framework, scVI-3D, to account for scHi-C specific biases. In benchmarking experiments, BandNorm yields leading performances in a time and memory efficient manner for cell-type separation, identification of interacting loci, and recovery of cell-type relationships, while scVI-3D exhibits advantages for rare cell types and under high sparsity scenarios. Application of BandNorm coupled with gene-associating domain analysis reveals scRNA-seq validated sub-cell type identificGenome biologyNormalization and de-noising of single-cell Hi-C data with BandNorm and scVI-3D.PMC9575231HG003747R21 HG011371R01 HG003747HG011371Zheng YShen SKeles SfalseNormalization and de-noising of single-cell Hi-C data with BandNorm and scVI-3D.Single-cell high-throughput chromatin conformation capture methodologies (scHi-C) enable profiling of long-range genomic interactions. However, data from these technologies are prone to technical noise and biases that hinder downstream analysis. We develop a normalization approach, BandNorm, and a deep generative modeling framework, scVI-3D, to account for scHi-C specific biases. In benchmarking experiments, BandNorm yields leading performances in a time and memory efficient manner for cell-type separation, identification of interacting loci, and recovery of cell-type relationships, while scVI-3D exhibits advantages for rare cell types and under high sparsity scenarios. Application of BandNorm coupled with gene-associating domain analysis reveals scRNA-seq validated sub-cell type identific2022-01-01T00:00:00Z2022 Oct2026-05-28T01:12:23.374Z2024-10-18T22:31:48.082ZS-EPMC95752313625382810.1186/s13059-022-02774-z