Using machine learning to detect the differential usage of novel gene isoforms

BACKGROUND: Differential isoform usage is an important driver of inter-individual phenotypic diversity and is linked to various diseases and traits. However, accurately detecting the differential usage of different gene transcripts between groups can be difficult, in particular in less well annotated genomes where the spectrum of transcript isoforms is largely unknown. RESULTS: We investigated whether machine learning approaches can detect differential isoform usage based purely on the distribution of reads across a gene region. We illustrate that gradient boosting and elastic net approaches can successfully identify large numbers of genes showing potential differential isoform usage between Europeans and Africans, that are enriched among relevant biological pathways and significantly overlap those identified by previous approaches. We demonstrate that diversity at the 3′ and 5′ ends of genes are primary drivers of these differences between populations. CONCLUSION: Machine learning methods can effectively detect differential isoform usage from read fraction data, and can provide novel insights into the biological differences between groups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04576-3.