Self-supervised pretraining (SSP) has been recognized as a method to enhance prediction accuracy in various downstream tasks. However, its efficacy for DNA sequences remains somewhat constrained. This limitation stems primarily from the fact that most existing SSP approaches in genomics focus on masked language modeling of individual sequences, neglecting the crucial aspect of encoding statistics across multiple sequences. To overcome this challenge, we introduce an innovative deep neural network model, which incorporates collaborative learning between a `student' and a `teacher' subnetwork. In this model, the student subnetwork employs masked learning on nucleotides and progressively adapts its parameters to the teacher subnetwork through an exponential moving average approach. Concurrently, both subnetworks engage in contrastive learning, deriving insights from two augmented representations of the input sequences. This self-distillation process enables our model to effectively assimilate both contextual information from individual sequences and distributional data across the sequence population. We validated our approach with preliminary pretraining using the human reference genome, followed by applying it to 20 downstream inference tasks. The empirical results from these experiments demonstrate that our novel method significantly boosts inference performance across the majority of these tasks. Our code is available at https://github.com/wiedersehne/FinDNA.

Sequential data naturally have different lengths in many domains, with some very long sequences. As an important modeling tool, neural attention should capture long-range interaction in such sequences. However, most existing neural attention models admit only short sequences, or they have to employ chunking or padding to enforce a constant input length. Here we propose a simple neural network building block called ChordMixer which can model the attention for long sequences with variable lengths. Each ChordMixer block consists of a positionwise rotation layer without learnable parameters and an element-wise MLP layer. Repeatedly applying such blocks forms an effective network backbone that mixes the input signals towards the learning targets. We have tested ChordMixer on the synthetic adding problem, long document classification, and DNA sequence-based taxonomy classification. The experiment results show that our method substantially outperforms other neural attention models. Sequential data appear widely in data science. In many domains, the sequences have a diverse distribution of lengths. Meanwhile, long-range interactions between DNA elements are common and can be up to 20,000 bases away (Gasperini et al., 2020). Modeling interactions in such sequences is a fundamental problem in machine learning and brings great challenges to attention approaches based on deep neural networks. Most existing neural attention methods cannot handle long sequences with different lengths. For efficient batch processing, architectures such as Transformer and its variants have been proposed, they usually assume constant input length.