“Just Saiyan: Tail-trimming Human Monkeypox Virus Assemblies Emphasizes Resolvable Regions in Inverted Terminal Repeats to Improve the Resolution of Reference and Production Genomes for Genomic Surveillance”

Abstract Our ability to track the spread of the human monkeypox virus (hMPXV) during the ongoing monkeypox (hMPX) outbreak of 2022 relies on the availability of high-quality reference genomes. However, the way the information content of these genomes is organized in genome databases leaves room for interpretation. A current limitation of hMPXV genomic analysis is that the variability occurring in the inverted terminal repeats (ITRs) cannot be effectively resolved. This is because of shortcomings of the leading short-read sequencing and reference-guided assembly and variant calling used in the ongoing global hMPXV outbreak surveillance effort. Here I propose ITR tail-trimming, a simple no-cost reframing of how we organize hMPXV reference genomes and future assemblies. This approach is based on long terminal repeat (LTR) tail-trimming, which is a common practice in HIV sequence analysis. The main point of repeat sequence trimming is to remove problematic sequences while paying attention to limitations of mapping and variant calling in remaining repeat-associated (but ideally no longer repetitive) sequence. ITR tail-trimming would neutralize ITRs as distracting features at the read- and assembly-levels, allowing the global community to focus our efforts to track variability across hMPXV genomes.