Genome Biol. 2023 Oct 20;24(1):240. doi: 10.1186/s13059-023-03038-0.
Diversity-generating and mobile genetic elements are key to microbial and viral evolution and can result in evolutionary leaps. State-of-the-art algorithms to detect these elements have limitations. Here, we introduce DIVE, a new reference-free approach to overcome these limitations using information contained in sequencing reads alone. We show that DIVE has improved detection power compared to existing reference-based methods using simulations and real data. We use DIVE to rediscover and characterize the activity of known and novel elements and generate new biological hypotheses about the mobilome. Building on DIVE, we develop a reference-free framework capable of de novo discovery of mobile genetic elements.