@Article{Raden_Wallach_Miladi-Struc_machi_learn-2021,
  author =	 {Raden, Martin and Wallach, Thomas and Miladi, Milad and 
                  Zhai, Yuanyuan and Kruger, Christina and Mossmann, Zoe J. 
                  and Dembny, Paul and Backofen, Rolf and Lehnardt, Seija},
  title =	 {Structure-aware machine learning identifies {microRNAs} 
                  operating as {Toll}-like receptor 7/8 ligands},
  journal =	 {RNA Biol},
  year =	 {2021},
  volume =	 {18},
  number =	 {sup1},
  pages =	 {268-277},
  user =	 {backofen},
  pmid =	 {34241565},
  doi = 	 {10.1080/15476286.2021.1940697},
  issn = 	 {1547-6286},
  issn = 	 {1555-8584},
  abstract =	 {MicroRNAs (miRNAs) can serve as activation signals for 
                  membrane receptors, a recently discovered function that is 
                  independent of the miRNAs' conventional role in 
                  post-transcriptional gene regulation. Here, we introduce a 
                  machine learning approach, BrainDead, to identify 
                  oligonucleotides that act as ligands for single-stranded 
                  RNA-detecting Toll-like receptors (TLR)7/8, thereby 
                  triggering an immune response. BrainDead was trained on 
                  activation data obtained from in vitro experiments on murine 
                  microglia, incorporating sequence and intra-molecular 
                  structure, as well as inter-molecular homo-dimerization 
                  potential of candidate RNAs. The method was applied to 
                  analyse all known human miRNAs regarding their potential to 
                  induce TLR7/8 signalling and microglia activation. We 
                  validated the predicted functional activity of subsets of 
                  high- and low-scoring miRNAs experimentally, of which a 
                  selection has been linked to Alzheimer's disease. High 
                  agreement between predictions and experiments confirms the 
                  robustness and power of BrainDead. The results provide new 
                  insight into the mechanisms of how miRNAs act as TLR 
                  ligands. Eventually, BrainDead implements a generic machine 
                  learning methodology for learning and predicting the 
                  functions of short RNAs in any context.}
}