DeepVRegulome: DNABERT-based deep-learning framework for predicting the functional impact of short genomic variants on the human regulome

• URL: http://arxiv.org/abs/2511.09026v1
• Date: Thu, 13 Nov 2025 01:26:40 GMT
• Title: DeepVRegulome: DNABERT-based deep-learning framework for predicting the functional impact of short genomic variants on the human regulome
• Authors: Pratik Dutta, Matthew Obusan, Rekha Sathian, Max Chao, Pallavi Surana, Nimisha Papineni, Yanrong Ji, Zhihan Zhou, Han Liu, Alisa Yurovsky, Ramana V Davuluri,
• Abstract summary: Deep VRegulome is a deep-learning method for prediction and interpretation of functionally disruptive variants in the human regulome.<n>We showcase its application on TCGA glioblastoma WGS dataset in prioritizing survival-associated mutations and regulatory regions.
• Score: 6.877744260030448
• License: http://creativecommons.org/licenses/by/4.0/
• Abstract: Whole-genome sequencing (WGS) has revealed numerous non-coding short variants whose functional impacts remain poorly understood. Despite recent advances in deep-learning genomic approaches, accurately predicting and prioritizing clinically relevant mutations in gene regulatory regions remains a major challenge. Here we introduce Deep VRegulome, a deep-learning method for prediction and interpretation of functionally disruptive variants in the human regulome, which combines 700 DNABERT fine-tuned models, trained on vast amounts of ENCODE gene regulatory regions, with variant scoring, motif analysis, attention-based visualization, and survival analysis. We showcase its application on TCGA glioblastoma WGS dataset in prioritizing survival-associated mutations and regulatory regions. The analysis identified 572 splice-disrupting and 9,837 transcription-factor binding site altering mutations occurring in greater than 10% of glioblastoma samples. Survival analysis linked 1352 mutations and 563 disrupted regulatory regions to patient outcomes, enabling stratification via non-coding mutation signatures. All the code, fine-tuned models, and an interactive data portal are publicly available.

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