Search arXiv⌕ Search
Home/Archive/arXiv

arXiv · 2606.07607

Position: Genomic Model Research Must Move Beyond Anecdotal Evaluation of Interpretability Methods

Shasha Zhou·Mingyu Huang·Ke Li
View original source ↗Read source document ↗Export metadata ↓

Abstract

Advances in machine learning and computational power have unlocked the predictive potential of the human genome, yet biologists now demand that these models also elucidate the underlying biological mechanisms. While interpretable machine learning (IML) techniques have been increasingly applied to bridge this gap, there has been a pervasive reliance on anecdotal validation: the vast majority of research relies on a single IML method and reports only isolated successful instances. Through a benchmarking study on transcription factor binding, we demonstrate the risks of current practices. We show that different IML methods can often (1) yield contradictory explanations for the same predictions, (2) fail to localize known regulatory motifs, and (3) fail to faithfully reflect the model's internal decision process. In light of this, we argue for a validation framework analogous to clinical trials: just as trials require rigorous design and adverse-event reporting, genomic interpretability must move beyond cherry-picked plausibility toward systematic assessment of consistency, faithfulness, and biological validity. To facilitate this, we propose a tiered framework to guide rigorous evaluation and reporting of genomic IML methods.

Explore related subjects

cs.LGq-bio.GN

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Shasha Zhou, Mingyu Huang, Ke Li. 2026-05-29. Position: Genomic Model Research Must Move Beyond Anecdotal Evaluation of Interpretability Methods. https://arxiv.org/abs/2606.07607

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Analysis of Regularized Learning in Banach Spaces for Linear-functional Data

This article delves into the study of the theory of regularized learning in Banach spaces for linear-functional data. It encompasses discussions on representer theorems, pseudo-approximation theorems, and convergence theorems. Regularized learning is designed to minimize regularized empirical risks over a Banach space. The empirical risks are calculated by utilizing training data and multi-loss functions. The input training data are composed of linear functionals in a predual space of the Banach space to capture discrete local information from multimodal data and multiscale models. Through the regularized learning, approximations of the exact solution to an unidentified or uncertain original problem are globally achieved. In the convergence theorems, the convergence of the approximate solutions to the exact solution is established through the utilization of the weak* topology of the Banach space. The theorems of regularized learning are utilized in the interpretation of classical machine learning, such as support vector machines and artificial neural networks.

cs.LG↗
arXiv2026

On Minimal Depth in Neural Networks

Understanding the relationship between the depth of a neural network and its representational capacity is a central problem in deep learning theory. In this work, we develop a geometric framework to analyze the expressivity of ReLU networks with the notion of depth complexity for convex polytopes. The depth of a polytope recursively quantifies the number of alternating convex hull and Minkowski sum operations required to construct it. This geometric perspective serves as a rigorous tool for deriving depth lower bounds and understanding the structural limits of deep neural architectures. We establish lower and upper bounds on the depth of polytopes, as well as tight bounds for classical families. These results yield two main consequences. First, we provide a purely geometric proof of the expressivity bound by Arora et al. (2018), confirming that $\lceil \log_2(n+1)\rceil$ hidden layers suffice to represent any continuous piecewise linear (CPWL) function. Second, we prove that, unlike general ReLU networks, convex polytopes do not admit a universal depth bound. Specifically, the depth of cyclic polytopes in dimensions $n \geq 4$ grows unboundedly with the number of vertices. This result implies that Input Convex Neural Networks (ICNNs) cannot represent all convex CPWL functions with a fixed depth, revealing a sharp separation in expressivity between ICNNs and standard ReLU networks.

cs.LG↗
arXiv2026

ELEMENT: Episodic and Lifelong Exploration via Maximum Entropy

Reinforcement learning agents depend on reward signals whose density is rarely under the designer's control, and when such signals are absent, an agent must generate its own drive to explore. State entropy maximization offers a principled objective for this, but existing methods break down at scale in two ways: the intrinsic reward vanishes once a state has been visited, discouraging revisits to the very gateways that lead onward, and estimating entropy over millions of accumulated observations becomes computationally prohibitive. We address both with Episodic and Lifelong Exploration via Maximum Entropy (ELEMENT), a multiscale intrinsically motivated framework for reward-free exploration that transfers to downstream tasks. ELEMENT couples lifelong entropy maximization with a complementary episodic term acting on a faster timescale. For the episodic term, we derive average episodic state entropy, an intrinsic reward that is the exact minimizer of a tractable upper bound on the reward-decomposition objective; for the lifelong term, we propose a $k$NN graph-based estimator that keeps entropy tractable without forgetting. ELEMENT consistently outperforms state-of-the-art intrinsic reward baselines on state coverage and unsupervised pre-training. Videos, code, and supplementary material: https://sites.google.com/view/element-rl.

cs.LG↗