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• W3124202287 abstract "Abstract Summary Mapping distal regulatory elements, such as enhancers, is the cornerstone for investigating genome evolution, understanding critical biological functions, and ultimately elucidating how genetic variations may influence diseases. Previous enhancer prediction methods have used either unsupervised approaches or supervised methods with limited training data. Moreover, past approaches have operationalized enhancer discovery as a binary classification problem without accurate enhancer boundary detection, producing low-resolution annotations with redundant regions and reducing the statistical power for downstream analyses (e.g., causal variant mapping and functional validations). Here, we addressed these challenges via a two-step model called DECODE. First, we employed direct enhancer activity readouts from novel functional characterization assays, such as STARR-seq, to train a deep neural network classifier for accurate cell-type-specific enhancer prediction. Second, to improve the annotation resolution (∼500 bp), we implemented a weakly-supervised object detection framework for enhancer localization with precise boundary detection (at 10 bp resolution) using gradient-weighted class activation mapping. Results Our DECODE binary classifier outperformed the state-of-the-art enhancer prediction methods by 24% in transgenic mouse validation. Further, DECODE object detection can condense enhancer annotations to only 12.6% of the original size, while still reporting higher conservation scores and genome-wide association study variant enrichments. Overall, DECODE improves the efficiency of regulatory element mapping with graphic processing units for deep-learning applications and is a powerful tool for enhancer prediction and boundary localization. Contact pi@gersteinlab.org" @default.
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• W3124202287 date "2021-01-28" @default.
• W3124202287 modified "2023-09-23" @default.
• W3124202287 title "DECODE: A Deep-learning Framework for Condensing Enhancers and Refining Boundaries with Large-scale Functional Assays" @default.
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• W3124202287 doi "https://doi.org/10.1101/2021.01.27.428477" @default.
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