MBE: model-based enrichment estimation and prediction for differential sequencing data

Abstract

Characterizing differences in sequences between two conditions, such as with and without drug exposure, using high-throughput sequencing data is a prevalent problem involving quantifying changes in sequence abundances, and predicting such differences for unobserved sequences. A key shortcoming of current approaches is their extremely limited ability to share information across related but non-identical reads. Consequently, they cannot use sequencing data effectively, nor be directly applied in many settings of interest. We introduce model-based enrichment (MBE) to overcome this shortcoming. We evaluate MBE using both simulated and real data. Overall, MBE improves accuracy compared to current differential analysis methods.

Keywords: Differential analysis; Machine learning; Protein engineering; Selection experiments; Sequencing.