Davide Greco, Konrad Rawlik
Large Language Models are increasingly popular in genomics due to their potential to decode complex biological sequences. Hence, researchers require a standardized benchmark to evaluate DNA Language Models (DNA LMs) capabilities. However, evaluating DNA LMs is a complex task that intersects genomic's domain-specific challenges and machine learning methodologies, where seemingly minor implementation details can significantly compromise benchmark validity. We demonstrate this through BEND (Benchmarking DNA Language Models), where hardware-dependent hyperparameters -- number of data loading workers and buffer sizes -- create spurious performance variations of up to 4% for identical models. The problem stems from inadequate data shuffling interacting with domain specific data characteristics. Experiments with three DNA language models (HyenaDNA, DNABERT-2, ResNet-LM) show these artifacts affect both absolute performance and relative model rankings. We propose a simple solution: pre-shuffling data before storage eliminates hardware dependencies while maintaining efficiency. This work highlights how standard ML practices can interact unexpectedly with domain-specific data characteristics, with broader implications for benchmark design in specialized domains.