# Uncertainty-Aware Deep Learning for Genomics Applications: Insights from an Empirical Study

arXiv: https://arxiv.org/abs/2608.11054 · HTML: https://mlsanity.com/paper/2608.11054/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 17 of its 53 references that are in the map.
- First posted on arXiv 11 Aug 2026.

## Builds on (most cited first, 17 of 17)

- [Dropout as a Bayesian Approximation: Representing Model Uncertainty in Deep Learning](https://mlsanity.com/paper/1506.02142/) (2015)
- [Simple and Scalable Predictive Uncertainty Estimation using Deep Ensembles](https://mlsanity.com/paper/1612.01474/) (2016)
- [Axiomatic Attribution for Deep Networks](https://mlsanity.com/paper/1703.01365/) (2017)
- [UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction](https://mlsanity.com/paper/1802.03426/) (2018)
- [What Uncertainties Do We Need in Bayesian Deep Learning for Computer Vision?](https://mlsanity.com/paper/1703.04977/) (2017)
- [Variational Inference: A Review for Statisticians](https://mlsanity.com/paper/1601.00670/) (2016)
- [Can You Trust Your Model's Uncertainty? Evaluating Predictive Uncertainty Under Dataset Shift](https://mlsanity.com/paper/1906.02530/) (2019)
- [Aleatoric and Epistemic Uncertainty in Machine Learning: An Introduction to Concepts and Methods](https://mlsanity.com/paper/1910.09457/) (2019)
- [A Review of Uncertainty Quantification in Deep Learning: Techniques, Applications and Challenges](https://mlsanity.com/paper/2011.06225/) (2020)
- [A Gentle Introduction to Conformal Prediction and Distribution-Free Uncertainty Quantification](https://mlsanity.com/paper/2107.07511/) (2021)
- [Weight Uncertainty in Neural Networks](https://mlsanity.com/paper/1505.05424/) (2015)
- [Metrics reloaded: Recommendations for image analysis validation](https://mlsanity.com/paper/2206.01653/) (2022)
- [Flipout: Efficient Pseudo-Independent Weight Perturbations on Mini-Batches](https://mlsanity.com/paper/1803.04386/) (2018)
- [Better Uncertainty Calibration via Proper Scores for Classification and Beyond](https://mlsanity.com/paper/2203.07835/) (2022)
- [A Systematic Comparison of Bayesian Deep Learning Robustness in Diabetic Retinopathy Tasks](https://mlsanity.com/paper/1912.10481/) (2019)
- [Explaining Deep Neural Networks and Beyond: A Review of Methods and Applications](https://mlsanity.com/paper/2003.07631/) (2020)
- [Arctique: An artificial histopathological dataset unifying realism and controllability for uncertainty quantification](https://mlsanity.com/paper/2411.07097/) (2024)

## Abstract (arXiv)

Deep learning models have emerged as the standard computational tool for a wide range of applications in genomics. Yet, uncertainty quantification (UQ) -- and more specifically, the reliability of different uncertainty estimates in this domain -- has received little systematic attention. This work presents an empirical analysis of UQ in deep learning models, focusing on genomics applications. In a series of experiments, we contrast Deep Ensembles, Bayesian Neural Networks, and Monte Carlo-dropout methods. We assess their ability to quantify uncertainty in different scenarios, accounting for common dataset characteristics in two genomic application areas and modalities: sequence-to-activity models, and single-cell expression analysis. Our systematic comparison framework provides guidelines for the applicability and reliability of UQ methods in genomics, highlighting their strengths and limitations in different scenarios. We show that Bayesian Neural Networks are better at capturing uncertainty caused by strong class imbalance and out-of-distribution data in genomics, despite their computational disadvantages. Moreover, we show how uncertainty scores can be used to select high-quality predictions in protein-RNA interactions.