Interpretable DNA Sequence Classification via Dynamic Feature Generation in Decision Trees

Fuente: arXiv
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Autores principales: Huynh, Nicolas, Kacprzyk, Krzysztof, Sheridan, Ryan, Bentley, David, van der Schaar, Mihaela
Formato: Preprint
Publicado: 2026
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author Huynh, Nicolas
Kacprzyk, Krzysztof
Sheridan, Ryan
Bentley, David
van der Schaar, Mihaela
author_facet Huynh, Nicolas
Kacprzyk, Krzysztof
Sheridan, Ryan
Bentley, David
van der Schaar, Mihaela
contents The analysis of DNA sequences has become critical in numerous fields, from evolutionary biology to understanding gene regulation and disease mechanisms. While deep neural networks can achieve remarkable predictive performance, they typically operate as black boxes. Contrasting these black boxes, axis-aligned decision trees offer a promising direction for interpretable DNA sequence analysis, yet they suffer from a fundamental limitation: considering individual raw features in isolation at each split limits their expressivity, which results in prohibitive tree depths that hinder both interpretability and generalization performance. We address this challenge by introducing DEFT, a novel framework that adaptively generates high-level sequence features during tree construction. DEFT leverages large language models to propose biologically-informed features tailored to the local sequence distributions at each node and to iteratively refine them with a reflection mechanism. Empirically, we demonstrate that DEFT discovers human-interpretable and highly predictive sequence features across a diverse range of genomic tasks.
format Preprint
id arxiv_https___arxiv_org_abs_2604_12060
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Interpretable DNA Sequence Classification via Dynamic Feature Generation in Decision Trees
Huynh, Nicolas
Kacprzyk, Krzysztof
Sheridan, Ryan
Bentley, David
van der Schaar, Mihaela
Machine Learning
Artificial Intelligence
Genomics
The analysis of DNA sequences has become critical in numerous fields, from evolutionary biology to understanding gene regulation and disease mechanisms. While deep neural networks can achieve remarkable predictive performance, they typically operate as black boxes. Contrasting these black boxes, axis-aligned decision trees offer a promising direction for interpretable DNA sequence analysis, yet they suffer from a fundamental limitation: considering individual raw features in isolation at each split limits their expressivity, which results in prohibitive tree depths that hinder both interpretability and generalization performance. We address this challenge by introducing DEFT, a novel framework that adaptively generates high-level sequence features during tree construction. DEFT leverages large language models to propose biologically-informed features tailored to the local sequence distributions at each node and to iteratively refine them with a reflection mechanism. Empirically, we demonstrate that DEFT discovers human-interpretable and highly predictive sequence features across a diverse range of genomic tasks.
title Interpretable DNA Sequence Classification via Dynamic Feature Generation in Decision Trees
topic Machine Learning
Artificial Intelligence
Genomics
url https://arxiv.org/abs/2604.12060