ArticleProceedings of the National Academy of Sciences of the United States of America2017
De novo prediction of human chromosome structures: Epigenetic marking patterns encode genome architecture.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.
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Who cites it
151 citing papers in PubMed.
- Euchromatin forms condensed domains with short active regions on the surface.Nature genetics · 2026Article
- Hybrid CNN and multi-head attention model for analyzing epigenetic mechanisms and gene expression across fungal phylogenetic distances.iScience · 2026Article
- Effects of chromatin-lamina attachment on extra-long-range chromatin interactions.Biophysical journal · 2026Article
- Modeling the spatial organization of replicated chromosomes in yeast reveals a loose asymmetric cohesion between sister chromatids.Nucleic acids research · 2026Article
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- THC-net: an attention-based deep learning model for chromatin compartment prediction from histone modifications.BMC bioinformatics · 2026Article
- Simultaneous modeling of chromatin conformation changes from multiple single-cell interaction maps with ChromMovie.Genome research · 2026Article
- Porcine MutBERT: a family of lightweight genomic foundation models for functional element prediction in pigs.Briefings in bioinformatics · 2026Article
- Investigating Phase Separation in Genome Folding via Multiscale Computational Modeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- An experimentally-informed polymer model reveals high resolution organization of genomic loci.Nature communications · 2026Article
- A data-driven chromatin model reveals spatial and dynamic features of genome organization.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- ChromNet: A Multi-Task Learning Framework for Cross-Cell Type Prediction of 3D Chromatin Interactions Using Epigenetic Signals.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genome-wide modeling of DNA replication in space and time confirms the emergence of replication specific patterns in vivo in eukaryotes.Genome biology · 2025Article
- Understanding the physical processes behind DNA-DNA proximity ligation assays.Research square · 2025Article
- Epigenetics is all you need: A transformer to decode chromatin structural compartments from the epigenome.PLoS computational biology · 2025Article
- Physical models reveal indirect reader protein interactions that facilitate epigenetic crosstalk.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Transcriptional condensates encode a "golden mean" to optimize enhancer-promoter communication across genomic distances.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
91 more citing papers are in PubMed but not listed here.
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5 authors.
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Abstract
Inside the cell nucleus, genomes fold into organized structures that are characteristic of cell type. Here, we show that this chromatin architecture can be predicted de novo using epigenetic data derived from chromatin immunoprecipitation-sequencing (ChIP-Seq). We exploit the idea that chromosomes encode a 1D sequence of chromatin structural types. Interactions between these chromatin types determine the 3D structural ensemble of chromosomes through a process similar to phase separation. First, a neural network is used to infer the relation between the epigenetic marks present at a locus, as assayed by ChIP-Seq, and the genomic compartment in which those loci reside, as measured by DNA-DNA proximity ligation (Hi-C). Next, types inferred from this neural network are used as an input to an energy landscape model for chromatin organization [Minimal Chromatin Model (MiChroM)] to generate an ensemble of 3D chromosome conformations at a resolution of 50 kilobases (kb). After training the model, dubbed Maximum Entropy Genomic Annotation from Biomarkers Associated to Structural Ensembles (MEGABASE), on odd-numbered chromosomes, we predict the sequences of chromatin types and the subsequent 3D conformational ensembles for the even chromosomes. We validate these structural ensembles by using ChIP-Seq tracks alone to predict Hi-C maps, as well as distances measured using 3D fluorescence in situ hybridization (FISH) experiments. Both sets of experiments support the hypothesis of phase separation being the driving process behind compartmentalization. These findings strongly suggest that epigenetic marking patterns encode sufficient information to determine the global architecture of chromosomes and that de novo structure prediction for whole genomes may be increasingly possible.
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