PubMed HealthSearch

PubMed · 40036975

EPIPDLF: a pretrained deep learning framework for predicting enhancer-promoter interactions.

Abstract

MOTIVATION: Enhancers and promoters, as regulatory DNA elements, play pivotal roles in gene expression, homeostasis, and disease development across various biological processes. With advancing research, it has been uncovered that distal enhancers may engage with nearby promoters to modulate the expression of target genes. This discovery holds significant implications for deepening our comprehension of various biological mechanisms. In recent years, numerous high-throughput wet-lab techniques have been created to detect possible interactions between enhancers and promoters. However, these experimental methods are often time-intensive and costly. RESULTS: To tackle this issue, we have created an innovative deep learning approach, EPIPDLF, which utilizes advanced deep learning techniques to predict EPIs based solely on genomic sequences in an interpretable manner. Comparative evaluations across six benchmark datasets demonstrate that EPIPDLF consistently exhibits superior performance in EPI prediction. Additionally, by incorporating interpretable analysis mechanisms, our model enables the elucidation of learned features, aiding in the identification and biological analysis of important sequences. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at: https://github.com/xzc196/EPIPDLF.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Zhichao Xiao, Yan Li, Yijie Ding, Liang Yu. 2025-05-06. EPIPDLF: a pretrained deep learning framework for predicting enhancer-promoter interactions.. https://doi.org/10.1093/bioinformatics%2Fbtae716

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Decoding TnsC Filament Assembly in CRISPR-Associated Transposons Using Interpretable Deep Learning and Molecular Simulations.

CRISPR-associated transposons (CASTs) enable programmable DNA integration, yet how the TnsC regulator forms processive filaments on DNA to coordinate RNA-guided transposition in type V-K CAST systems remains unknown. Here, we integrate large-scale molecular simulations, interpretable deep learning using graph attention networks (GATs), and causal inference analyses to define the molecular determinants of TnsC filament nucleation and elongation. We show that TnsC nucleates by inducing localized DNA deformation that propagates along extended filaments, with Granger causality revealing that TnsC motions precede and predict DNA deformation. Interpretable GAT models demonstrate that elongation is determined during early recognition between incoming and DNA-bound subunits, followed by structural reorganization that regenerates the recruitment interface and enables processive assembly. These results elucidate the molecular mechanism of processive TnsC filament assembly and explain why isolated TnsC filaments preferentially elongate in the 5' → 3' direction, while accessory transposition factors can reshape the interaction landscape and alter filament growth polarity. Together, these findings advance our understanding of CAST function and inform the engineering of programmable DNA integration platforms. Beyond CAST systems, this work introduces an interpretable GAT approach as a general and transferable deep learning strategy for uncovering molecular mechanisms in biological systems, while demonstrating the power of causal inference for dissecting directional relationships in molecular dynamics.

Deep Learning

Using deep learning models as a genetic architecture for the simulation of breeding schemes.

In several simulation studies, long-term selection led to the rapid depletion of genetic variance. These outcomes differ from real-life observations that we aim to replicate, thereby highlighting a fundamental limitation of current classical quantitative genetic simulation models. Deep learning (DL) models have demonstrated promising results in capturing complex interactions essential for maintaining genetic variance; thus, we hypothesize that DL-based genetic simulation models may preserve more genetic variance than classical models, because the biological pathways underlying complex traits exhibit interactions that classical models ignore. The primary objective of this study was to introduce alternative DL-based genetic simulation models and compare them with classical genetic simulation models in terms of their retention of additive genetic variance under truncation selection in a simulated full-sib pig breeding scheme using real haplotypes as founders. After 20 generations of directional truncation selection, the classical models (A, ADAA, and ADAAADDD) retained between 55% and 64% of their initial additive genetic variance. In contrast, while the DL_simple model lost all its additive variance, the DL medium retained 92% to 98% of its additive variance, and the DL_complex model's initial additive variance increased by 296% to 314%. This paper introduces DL-based genetic simulation models and concludes that their ability to retain additive genetic variance depends on the models' architectural complexity. When sufficiently complex, DL-based models exhibit greater retention of additive genetic variance because they intrinsically capture epistatic interactions that are converted into additive variance, as selection progresses, thus, affirming the role of non-additive genetic effects in maintaining long-term genetic variation.

Deep Learning

High-accuracy SNV calling for bacterial isolates using deep learning with AccuSNV.

Accurate detection of mutations within bacterial species is critical for fundamental studies of microbial evolution, reconstruction of transmission events, and identification of antimicrobial resistance mutations. Although many tools have been developed to identify single-nucleotide variants (SNVs) from whole-genome sequencing, they often suffer from high false-positive rates owing to the complexity of bacterial genomes and the need for different filtering cutoffs across sample types and sequencing depths. As data sets increase in size, the manual filtering required for high accuracy presents a significant obstacle. Here, we present AccuSNV, a novel deep learning-based tool for high-precision and automated bacterial SNV calling. Unlike traditional methods that process one sample at a time, AccuSNV leverages a convolutional neural network (CNN) that integrates alignment information across multiple samples, enhancing precision through learned across-sample patterns. We evaluate AccuSNV against seven popular SNV-calling tools using simulated data from six bacterial species with varied sequencing depths, numbers of isolates, mutations, and divergence levels. To further validate its real-world utility, we test AccuSNV on multiple curated bacterial data sets containing reported SNVs. In both simulated and real-world scenarios, AccuSNV consistently achieves the best performance. Moreover, AccuSNV provides comprehensive user-friendly downstream analysis modules and outputs, including mutation annotation information, phylogenetic inference, d N/d S calculations, and optional manual filtering. Together with the automated deep learning-based calling, these features make AccuSNV broadly accessible to users with different levels of computational expertise.

Deep Learning