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The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Structure-aware machine learning identifies microRNAs operating as Toll-like receptor 7/8 ligands

Raden, Martin, Wallach, Thomas, Miladi, Milad, Zhai, Yuanyuan, Krüger, Christina, Mossmann, Zoé J., Dembny, Paul, Backofen, Rolf, Lehnardt, Seija·2021·RNA Biology
DOI 10.1080/15476286.2021.1940697PMC PMC8677043
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Figure 1. Depiction of BrainDead’s workflow of feature generation (centre), model trainingand candidate classification (bottom)
Figure 1. Depiction of BrainDead’s workflow of feature generation (centre), model trainingand candidate classification (bottom)CC BY-NC-ND · PubMed Central
Figure 2. Illustration of context-sensitive k-mer counting for feature generation. One of the two occurrences of a fictive k-mer (blue bar) within an RNA (grey bar) is masked by intra-molecular structure formation while both locations are involved in homo-dimerization. See Supplementary Material for a miRNA example
Figure 2. Illustration of context-sensitive k-mer counting for feature generation. One of the two occurrences of a fictive k-mer (blue bar) within an RNA (grey bar) is masked by intra-molecular structure formation while both locations are involved in homo-dimerization. See Supplementary Material for a miRNA exampleCC BY-NC-ND · PubMed Central
Figure 3. Distribution of BrainDead scores and predicted activation potential (orange and blue) for all 2,656 human miRNAs annotated in mirBase. The bottom histogram (light blue) provides the distribution of 93 BrainDead scores of Alzheimer’s disease (AD)-associated miRNAs according to the PhenomiR database
Figure 3. Distribution of BrainDead scores and predicted activation potential (orange and blue) for all 2,656 human miRNAs annotated in mirBase. The bottom histogram (light blue) provides the distribution of 93 BrainDead scores of Alzheimer’s disease (AD)-associated miRNAs according to the PhenomiR databaseCC BY-NC-ND · PubMed Central
Figure 4. Experimentally assessed TNF-α release from microglia. (a) list 1 – miRNA candidates that were selected based on BrainDead score only and (b) list 2 – AD-associated miRNAs. miRNAs are arranged by ascending BrainDead prediction score. Blue and orange colouring refers to BrainDead prediction, i.e. activating (high-5) and non-activating (low-5), respectively. Control conditions are indicated by grey colour. Microglia were exposed to 10 µg/ml of the indicated miRNA mimic for 24 h. The established TLR7 agonist loxoribine (1 mM) and the TLR4 agonist lipopolysaccharide (LPS, 100 ng/ml) served as positive control for microglial activation. Control mutant oligonucleotide (10 µg/ml), unstimulated cells, and the transfection agent LyoVec were used as negative control. Bars represent mean values ± SEM (n = 4) of depicted measurements (dots). **P < 0.01; ****P < 0.0001 compared to unstimulated condition, two-tailed Student’s t-test
Figure 4. Experimentally assessed TNF-α release from microglia. (a) list 1 – miRNA candidates that were selected based on BrainDead score only and (b) list 2 – AD-associated miRNAs. miRNAs are arranged by ascending BrainDead prediction score. Blue and orange colouring refers to BrainDead prediction, i.e. activating (high-5) and non-activating (low-5), respectively. Control conditions are indicated by grey colour. Microglia were exposed to 10 µg/ml of the indicated miRNA mimic for 24 h. The established TLR7 agonist loxoribine (1 mM) and the TLR4 agonist lipopolysaccharide (LPS, 100 ng/ml) served as positive control for microglial activation. Control mutant oligonucleotide (10 µg/ml), unstimulated cells, and the transfection agent LyoVec were used as negative control. Bars represent mean values ± SEM (n = 4) of depicted measurements (dots). **P < 0.01; ****P < 0.0001 compared to unstimulated condition, two-tailed Student’s t-testCC BY-NC-ND · PubMed Central
Figure 5. Relation of activity measurements from mouse microglia and mTLR7 reporter cells. Each point represents a miRNA from the respective candidate list, i.e. list 1 includes candidates that were selected based on BrainDead score only (circles), while list 2 includes AD-associated miRNAs classified by BrainDead (squares). TNF-α concentrations (mouse microglia, y-axis) and SEAP activity expressed as fold change (mTLR7 reporter activation, x-axis) averaged from four replicates are shown. The annotated numbers indicate the ranking predicted by BrainDead for the high-5 activating miRNAs of the two lists. See Figure S7 for an extended version of the plot
Figure 5. Relation of activity measurements from mouse microglia and mTLR7 reporter cells. Each point represents a miRNA from the respective candidate list, i.e. list 1 includes candidates that were selected based on BrainDead score only (circles), while list 2 includes AD-associated miRNAs classified by BrainDead (squares). TNF-α concentrations (mouse microglia, y-axis) and SEAP activity expressed as fold change (mTLR7 reporter activation, x-axis) averaged from four replicates are shown. The annotated numbers indicate the ranking predicted by BrainDead for the high-5 activating miRNAs of the two lists. See Figure S7 for an extended version of the plotCC BY-NC-ND · PubMed Central

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Citations

Cites

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Metadata

Authors
Raden, M., Wallach, T., Miladi, M., Zhai, Y., Krüger, C., Mossmann, Z. J., Dembny, P., Backofen, R., & Lehnardt, S.
Affiliations
  • Bioinformatics Group, Department of Computer Science, University of Freiburg, Freiburg, Germany
  • Institute of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
ORCID
Venue
RNA Biology
Publisher
Informa UK Limited
Published
2021-07-09
Volume
18
Issue
sup1
Pages
268-277
ISSN
  • 1547-6286
  • 1555-8584
DOI
10.1080/15476286.2021.1940697
PMC
PMC8677043
Cited by
14
References
6
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (unspecified)
Funders
Deutsche Forschungsgemeinschaft (BA2168/16-1, BA2168/21-1, SFB-TRR167/B03, CIBSS-EXC-2189-Project ID 390939984, LE2420/2-1, BA2168/3-3)

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