Microbial and autoantibody immunogenic repertoires in TIF1? autoantibody positive dermatomyositis

Spyridon Megremis; Thomas Walker; Xiaotong He; James O'Sullivan; William E.R. Ollier; Hector Chinoy; Neil Pendleton; Antony Payton; Lynne Hampson; Ian Hampson; Janine Lamb

We focused our further analysis on the DM P20 and HC P20 subgroups. To stratify the microbial species based on their potential significance in DM, we first normalised the number of NGS reads against the total number of epitopes per microbial species (NGSRe-norm) ( Figure S3A -S3D), and studied the relative ranking of viruses and cellular microbes ( Figure 3A & 3B) . Secondly, we evaluated the . CC-BY-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.25.007534 doi: bioRxiv preprint mean NGSRe-norm at the viral family taxonomy level ( Figure 4D & 4E) , and, thirdly, we recorded the total number of species contributing to each family ( Figure 4D & 4E) (Table S2 ). Thus, we tested for potential high taxonomy-level organisation of microbes in DM. Ranking the microbial species based on decreasing NSGRe-norm we observed that viruses were over-represented in the top 10% of dominant microbial species relative to the total number of viral species present in both DM and HC ( Figure 3A & 3B). Specifically, 18.47% and 17.93% of viral species were present in the top 10% of microbes in the DM P20 and HC P20, respectively ( Figure The HC viral IgOme profile contained a higher proportion of total double stranded DNA (dsDNA) (NGSRe-norm 46.35% vs. 39.68%) and single stranded RNA (ssRNA) (NGSRe-norm 43.70% vs. 35.85%) than DM ( Figure 4A & 4B). The DM viral IgOme contained a higher proportion of ssDNA viruses (NGSRe-norm 15.95% vs. 3.10%) and RNA reverse-transcribing retroviruses (NGSRe-norm 7.16% vs.