# Extending Sequence Length is Not All You Need: Effective Integration of Multimodal Signals for Gene Expression Prediction

arXiv: https://arxiv.org/abs/2602.21550 · HTML: https://mlsanity.com/paper/2602.21550/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 13 of its 51 references that are in the map.
- First posted on arXiv 25 Feb 2026.

## Builds on (most cited first, 13 of 13)

- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Mamba: Linear-Time Sequence Modeling with Selective State Spaces](https://mlsanity.com/paper/2312.00752/) (2023)
- [Learning Deep Features for Discriminative Localization](https://mlsanity.com/paper/1512.04150/) (2015)
- [Understanding Contrastive Representation Learning through Alignment and Uniformity on the Hypersphere](https://mlsanity.com/paper/2005.10242/) (2020)
- [HyenaDNA: Long-Range Genomic Sequence Modeling at Single Nucleotide Resolution](https://mlsanity.com/paper/2306.15794/) (2023)
- [Caduceus: Bi-Directional Equivariant Long-Range DNA Sequence Modeling](https://mlsanity.com/paper/2403.03234/) (2024)
- [Interventional Few-Shot Learning](https://mlsanity.com/paper/2009.13000/) (2020)
- [Understanding and Mitigating Bottlenecks of State Space Models through the Lens of Recency and Over-smoothing](https://mlsanity.com/paper/2501.00658/) (2024)
- [VQDNA: Unleashing the Power of Vector Quantization for Multi-Species Genomic Sequence Modeling](https://mlsanity.com/paper/2405.10812/) (2024)
- [Interventional Contrastive Learning with Meta Semantic Regularizer](https://mlsanity.com/paper/2206.14702/) (2022)
- [Regulatory DNA sequence Design with Reinforcement Learning](https://mlsanity.com/paper/2503.07981/) (2025)
- [SPACE: Your Genomic Profile Predictor is a Powerful DNA Foundation Model](https://mlsanity.com/paper/2506.01833/) (2025)
- [Learning to Discover Regulatory Elements for Gene Expression Prediction](https://mlsanity.com/paper/2502.13991/) (2025)

## Built on by (most cited first, 1 of 1)

- [PaperFit: Vision-in-the-Loop Typesetting Optimization for Scientific Documents](https://mlsanity.com/paper/2605.10341/) (2026)

## Abstract (arXiv)

Gene expression prediction, which predicts mRNA expression levels from DNA sequences, presents significant challenges. Previous works often focus on extending input sequence length to locate distal enhancers, which may influence target genes from hundreds of kilobases away. Our work first reveals that for current models, long sequence modeling can decrease performance. Even carefully designed algorithms only mitigate the performance degradation caused by long sequences. Instead, we find that proximal multimodal epigenomic signals near target genes prove more essential. Hence we focus on how to better integrate these signals, which has been overlooked. We find that different signal types serve distinct biological roles, with some directly marking active regulatory elements while others reflect background chromatin patterns that may introduce confounding effects. Simple concatenation may lead models to develop spurious associations with these background patterns. To address this challenge, we propose Prism, a framework that learns multiple combinations of high-dimensional epigenomic features to represent distinct background chromatin states and uses backdoor adjustment to mitigate confounding effects. Our experimental results demonstrate that proper modeling of multimodal epigenomic signals achieves state-of-the-art performance using only short sequences for gene expression prediction.