Language Modelling Techniques for Analysing the Impact of Human Genetic Variation

Interpreting the effects of variants within the human genome and proteome is essential for analysing disease risk, predicting medication response, and developing personalised health interventions. Due to the intrinsic similarities between the structure of natural languages and genetic sequences, natural language processing techniques have demonstrated great applicability in computational variant effect prediction. In particular, the advent of the Transformer has led to significant advancements in the field. However, transformer-based models are not without their limitations, and a number of extensions and alternatives have been developed to improve results and enhance computational efficiency. This systematic review investigates over 50 different language modelling approaches to computational variant effect prediction over the past decade, analysing the main architectures, and identifying key trends and future directions. Benchmarking of the reviewed models remains unachievable at present, primarily due to the lack of shared evaluation frameworks and data sets.