Improving Genomic Models via Task-Specific Self-Pretraining

Abstract: Pretraining DNA LLMs (DNALMs) on the full human genome is resource-intensive, yet often considered necessary for strong downstream performance. Inspired by recent findings in NLP and long-context modeling, we explore an alternative: self-pretraining on task-specific, unlabeled data. Using the BEND benchmark, we show that DNALMs trained with self-pretraining match or exceed the performance of models trained from scratch under identical compute. While genome-scale pretraining may still offer higher absolute performance, task-specific self-pretraining provides a practical and compute-efficient strategy for building stronger supervised baselines.