Year: 2021
Type: article
Abstract: The 5' untranslated region plays a key role in regulating mRNA translation and consequently protein abundance. Therefore, accurate modeling of 5'UTR regulatory sequences shall provide insights into translational control mechanisms and help interpret genetic variants. Recently, a model was trained on a massively parallel reporter assay to predict mean ribosome load (MRL)-a proxy for translation rate-directly from 5'UTR sequence with a high degree of accuracy. However, this model is restricted to sequence lengths investigated in the reporter assay and therefore cannot be applied to the majority of human sequences without a substantial loss of information. Here, we introduced frame pooling, a novel neural network operation that enabled the development of an MRL prediction model for 5'UTRs of any length. Our model shows state-of-the-art performance on fixed length randomized sequences, while offering better generalization performance on longer sequences and on a variety of translation-related genome-wide datasets. Variant interpretation is demonstrated on a 5'UTR variant of the gene HBB associated with beta-thalassemia. Frame pooling could find applications in other bioinformatics predictive tasks. Moreover, our model, released open source, could help pinpoint pathogenic genetic variants.
Source: PLoS Computational Biology
Authors: Alexander Karollus, Žiga Avsec, Julien Gagneur
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,575
OpenAlex ID: W3163562839