@article{Raden-2021-BrainDead, year = {2021}, volume = {18}, number = {sup1}, pages = {268-277}, doi = {10.1080/15476286.2021.1940697}, issn = {1547-6286}, issn = {1555-8584}, abstract = "{MicroRNAs (miRNAs) are about 22 nucleotides long and have been linked to various human diseases. They 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, the resident immune cells in the brain, incorporating sequence, intra-molecular structure, as well as inter-molecular homo-dimerization potential of candidate RNAs. It was applied to analyze all known human miRNAs regarding their potential to induce TLR7/8 signaling 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, the most common cause of dementia in humans. High agreement of predictions and experiments confirms the robustness and power of BrainDead. The results provide new insight into the mechanisms how miRNAs act as TLR ligands. Eventually, BrainDead implements a generic machine learning methodology for learning and predicting functions of short RNAs in any context.}", author = {Martin Raden and Thomas Wallach and Milad Miladi and Yuanyuan Zhai and Christina Kr\"{u}ger and Zoe J. Mossmann and Paul Dembny and Rolf Backofen and Seija Lehnardt}, title = {Structure-aware machine learning classification of oligonucleotide-induced immune response identifies micro{RNA}s operating as {Toll}-like receptor 7/8 ligands}, journal = {RNA Biology}, user = {mmann}, note = {(MR, TW, MM contributed equally)} }