Transposable element subfamily annotation has a reproducibility problem

摘要

Transposable element (TE) sequences are classified into families based on the reconstructed history of replication, and into subfamilies based on more fine-grained features that are often intended to capture family history. We evaluate the reliability of annotation with common subfamilies by assessing the extent to which subfamily annotation is reproducible in replicate copies created by segmental duplications in the human genome, and in homologous copies shared by human and chimpanzee. We find that standard methods annotate over 10% of replicates as belonging to different subfamilies, despite the fact that they are expected to be annotated as belonging to the same subfamily. Point mutations and homologous recombination appear to be responsible for some of this discordant annotation (particularly in the young Alu family), but are unlikely to fully explain the annotation unreliability. The surprisingly high level of disagreement in subfamily annotation of homologous sequences highlights a need for further research into definition of TE subfamilies, methods for representing subfamily annotation confidence of TE instances, and approaches to better utilizing such nuanced annotation data in downstream analysis.