# Explainable AI in Genomics: Transcription Factor Binding Site Prediction with Mixture of Experts

arXiv: https://arxiv.org/abs/2507.09754 · HTML: https://mlsanity.com/paper/2507.09754/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical and biomedical MoE, one of 12 directions in Mixture-of-experts.
- Builds on 21 of its 70 references that are in the map.
- First posted on arXiv 13 Jul 2025.

## Placed in

- Mixture-of-experts / [Medical and biomedical MoE](https://mlsanity.com/moe/medical-and-biomedical-moe/)

## Builds on (most cited first, 21 of 21)

- [Microsoft COCO: Common Objects in Context](https://mlsanity.com/paper/1405.0312/) (2014)
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- [A Unified Approach to Interpreting Model Predictions](https://mlsanity.com/paper/1705.07874/) (2017)
- [Outrageously Large Neural Networks: The Sparsely-Gated Mixture-of-Experts Layer](https://mlsanity.com/paper/1701.06538/) (2017)
- [Axiomatic Attribution for Deep Networks](https://mlsanity.com/paper/1703.01365/) (2017)
- [Optuna: A Next-generation Hyperparameter Optimization Framework](https://mlsanity.com/paper/1907.10902/) (2019)
- [Deep Inside Convolutional Networks: Visualising Image Classification Models and Saliency Maps](https://mlsanity.com/paper/1312.6034/) (2013)
- [Learning Important Features Through Propagating Activation Differences](https://mlsanity.com/paper/1704.02685/) (2017)
- [SmoothGrad: removing noise by adding noise](https://mlsanity.com/paper/1706.03825/) (2017)
- [YOLOv7: Trainable bag-of-freebies sets new state-of-the-art for real-time object detectors](https://mlsanity.com/paper/2207.02696/) (2022)
- [Robustness May Be at Odds with Accuracy](https://mlsanity.com/paper/1805.12152/) (2018)
- [Transformer Interpretability Beyond Attention Visualization](https://mlsanity.com/paper/2012.09838/) (2020)
- [From Anecdotal Evidence to Quantitative Evaluation Methods: A Systematic Review on Evaluating Explainable AI](https://mlsanity.com/paper/2201.08164/) (2022)
- [Recent Advances in Adversarial Training for Adversarial Robustness](https://mlsanity.com/paper/2102.01356/) (2021)
- [Learning Factored Representations in a Deep Mixture of Experts](https://mlsanity.com/paper/1312.4314/) (2013)
- [Secure and Robust Machine Learning for Healthcare: A Survey](https://mlsanity.com/paper/2001.08103/) (2020)
- [Robust Explainability: A Tutorial on Gradient-Based Attribution Methods for Deep Neural Networks](https://mlsanity.com/paper/2107.11400/) (2021)
- [Transformers in Time-series Analysis: A Tutorial](https://mlsanity.com/paper/2205.01138/) (2022)
- [How explainable are adversarially-robust CNNs?](https://mlsanity.com/paper/2205.13042/) (2022)
- [EvalAttAI: A Holistic Approach to Evaluating Attribution Maps in Robust and Non-Robust Models](https://mlsanity.com/paper/2303.08866/) (2023)
- [Comprehensive Evaluation of Deep Learning Architectures for Prediction of DNA/RNA Sequence Binding Specificities](https://mlsanity.com/paper/1901.10526/) (2019)

## Abstract (arXiv)

Transcription Factor Binding Site (TFBS) prediction is crucial for understanding gene regulation and various biological processes. This study introduces a novel Mixture of Experts (MoE) approach for TFBS prediction, integrating multiple pre-trained Convolutional Neural Network (CNN) models, each specializing in different TFBS patterns. We evaluate the performance of our MoE model against individual expert models on both in-distribution and out-of-distribution (OOD) datasets, using six randomly selected transcription factors (TFs) for OOD testing. Our results demonstrate that the MoE model achieves competitive or superior performance across diverse TF binding sites, particularly excelling in OOD scenarios. The Analysis of Variance (ANOVA) statistical test confirms the significance of these performance differences. Additionally, we introduce ShiftSmooth, a novel attribution mapping technique that provides more robust model interpretability by considering small shifts in input sequences. Through comprehensive explainability analysis, we show that ShiftSmooth offers superior attribution for motif discovery and localization compared to traditional Vanilla Gradient methods. Our work presents an efficient, generalizable, and interpretable solution for TFBS prediction, potentially enabling new discoveries in genome biology and advancing our understanding of transcriptional regulation.