MPXV intrahost variation in the context of APOBEC deamination: An initial look

MPXV intrahost variation in the context of APOBEC deamination: An initial look

Anton Nekrutenko |, Penn State, CEFE CNRS

APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) converts C in single stranded stretches of DNA or RNA to U resulting CT transition. Members of APOBEC family target specific sequence motifs: TC , CCC , TTC where the last base mutated to T , or TCW ( W = A / T ) where the middle base mutates to T (see Chen and MacCarthy 2014 ).

Recently O’Toole & Rambaut conducted a survey of potential APOBEC signatures in a set of MPXV genomes. If APOBEC is indeed partially responsible for introducing nucleotide changes to MPXV genome in humans, we should be able to observe these changes in intrahost samples with intermediate alternative allele frequencies.


The challenge is, of course, finding these data. Despite the fact that a number of datasets have been deposited to EBI SRA, recent indexing issues at EBI prevent download of these data. At the time of writing (June 13, 2022) the only available (the ones that can actually be downloaded) SRA datasets were:

BioProject Description Number of samples Platform
PRJNA844567 Second draft genome from Spain of the Monkeypox virus 2022 outbreak 1 ONT
PRJNA842892 Monkeypox virus from ongoing epidemic in UK (May-2022) 4 ONT
PRJNA844330 Full-Length Genome characterization of a monkeypox case in Northeast Italy 1 Illumina
PRJNA845087 Illumina whole-genome sequence of Monkeypox virus in a patient traveling from the Canary Islands to France 4 Illumina

Since Illumina data is more suitable for detection of low frequency variants (5% and up) we analyzed data provided by PRJNA845087 (also described here).


We analyzed PRJNA845087 using Galaxy workflows that have also been used in this study. The analysis artifacts can be examined and/or downloaded here:

Artifact Description Link
Galaxy History A complete record of the analysis with all starting and intermediate datasets
Variant list A tab-delimited list of variants used in this analysis [dataset]


The following image provides quick summary of the results. The interactive version of this image is here.

  • The majority of changes are C->T and G->A
  • While most of these changes are fixed, some exist in intermediate frequencies (can be seen in the interactive version).
  • Some change classes (e.g., T->C) only exist in intermediate frequencies

visualization (7)

We are waiting on more datasets becoming available to expand the interpretation of these results.