UniversalEPI: a generalized attention-based deep ensemble model to accurately predict enhancer-promoter interactions across diverse cell types and conditions

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Publicat a:bioRxiv (Jan 15, 2025)
Autor principal: Grover, Aayush
Altres autors: Zhang, Lin, Muser, Till, Häfliger, Simeon, Wang, Minjia, Yates, Josephine, Eliezer Van Allen, Theis, Fabian J, Ibarra, Ignacio L, Krymova, Ekaterina, Boeva, Valentina
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Cold Spring Harbor Laboratory Press
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LEADER 00000nab a2200000uu 4500
001 3132198702
003 UK-CbPIL
022 |a 2692-8205 
024 7 |a 10.1101/2024.11.22.624813  |2 doi 
035 |a 3132198702 
045 0 |b d20250115 
100 1 |a Grover, Aayush 
245 1 |a UniversalEPI: a generalized attention-based deep ensemble model to accurately predict enhancer-promoter interactions across diverse cell types and conditions 
260 |b Cold Spring Harbor Laboratory Press  |c Jan 15, 2025 
513 |a Working Paper 
520 3 |a Interactions between enhancers and gene promoters provide insights into gene regulation. Experimental techniques, including Hi-C, that map these enhancer-promoter interactions (EPIs), have high costs and labor requirements, which limits their use. Therefore, in silico methods have been developed to predict EPIs computationally, but there are challenges with the generalizability and accuracy of existing methods. Here, we introduce UniversalEPI, an attention-based deep ensemble model designed to provide uncertainty-aware predictions of EPIs up to 2 Mb apart, which can generalize across unseen cell types using only DNA sequence and chromatin accessibility (ATAC-seq) data. Benchmarking shows that UniversalEPI significantly outperforms existing approaches in accuracy and efficiency, even though it is a lightweight model that only assesses interactions between accessible chromatin regions. UniversalEPI enables statistical comparison of predicted interactions across conditions, which we demonstrated by tracking the dynamics of EPIs during human macrophage activation. We also used UniversalEPI to assess chromatin dynamics between different cancer cell states in human esophageal adenocarcinoma. Thus, UniversalEPI advances the accuracy and applicability of in silico 3D chromatin modeling to investigate chromatin dynamics in development and disease.Competing Interest StatementF.J.T. consults for Immunai Inc., Singularity Bio B.V., CytoReason Ltd, and Omniscope Ltd, and has ownership interest in Dermagnostix GmbH and Cellarity. I.L.I. currently works at Bioptimus.Footnotes* The manuscript text is updated for better clarity. Supplementary files added. 
653 |a Adenocarcinoma 
653 |a Transcription factors 
653 |a Cell differentiation 
653 |a Nucleotide sequence 
653 |a Macrophages 
653 |a Transcription activation 
653 |a Neural networks 
653 |a Chromatin 
653 |a Regulatory sequences 
653 |a Cell activation 
653 |a Esophageal cancer 
700 1 |a Zhang, Lin 
700 1 |a Muser, Till 
700 1 |a Häfliger, Simeon 
700 1 |a Wang, Minjia 
700 1 |a Yates, Josephine 
700 1 |a Eliezer Van Allen 
700 1 |a Theis, Fabian J 
700 1 |a Ibarra, Ignacio L 
700 1 |a Krymova, Ekaterina 
700 1 |a Boeva, Valentina 
773 0 |t bioRxiv  |g (Jan 15, 2025) 
786 0 |d ProQuest  |t Biological Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3132198702/abstract/embedded/H09TXR3UUZB2ISDL?source=fedsrch 
856 4 0 |3 Full text outside of ProQuest  |u https://www.biorxiv.org/content/10.1101/2024.11.22.624813v3