Self-supervised pre-training methods have brought remarkable breakthroughs in the understanding of text, image, and speech. Recent developments in genomics has also adopted these pre-training methods for genome understanding. However, they focus only on understanding haploid sequences, which hinders their applicability towards understanding genetic variations, also known as single nucleotide polymorphisms (SNPs), which is crucial for genome-wide association study. In this paper, we introduce SNP2Vec, a scalable self-supervised pre-training approach for understanding SNP. We apply SNP2Vec to perform long-sequence genomics modeling, and we evaluate the effectiveness of our approach on predicting Alzheimer’s disease risk in a Chinese cohort. Our approach significantly outperforms existing polygenic risk score methods and all other baselines, including the model that is trained entirely with haploid sequences.

Large pre-trained language models (LMs) have been widely adopted in biomedical and clinical domains, introducing many powerful LMs such as bio-lm and BioELECTRA. However, the applicability of these methods to real clinical use cases is hindered, due to the limitation of pre-trained LMs in processing long textual data with thousands of words, which is a common length for a clinical note. In this work, we explore long-range adaptation from such LMs with Longformer, allowing the LMs to capture longer clinical notes context. We conduct experiments on three n2c2 challenges datasets and a longitudinal clinical dataset from Hong Kong Hospital Authority electronic health record (EHR) system to show the effectiveness and generalizability of this concept, achieving ~10% F1-score improvement. Based on our experiments, we conclude that capturing a longer clinical note interval is beneficial to the model performance, but there are different cut-off intervals to achieve the optimal performance for different target variables.