miRNA Targets: From Prediction Tools to Experimental Validation
Abstract
:1. Introduction
2. miRNA Target Prediction
2.1. Predictive Methods
2.1.1. Strategies for de novo Predictions
- Seed pairing
- 8mer site: a perfect Watson-Crick match from nucleotide 2 to nucleotide 8 of the miRNA seed, with an “A” in mRNA opposite position 1;
- 7mer site: Watson-Crick match from nucleotide 2 to nucleotide 8 without the “A” opposite position 1;
- 7mer A1 site: Watson–Crick match from nucleotide 2 to nucleotide 7 with an A opposite position 1;
- 6mer site: position 2–7 match;
- 6mer site: position 3–8 match.
- 2.
- Thermodynamic stability
- 3.
- Evolutionary conservation
- 4.
- Accessibility of target site
- 5.
- Number of target sites in the same 3′-UTR
2.1.2. Machine Learning
- For every miRNA, identify the presumed binding site from validated mRNA targets (as positive) and non-targets (as negative).
- Extract features from these interactions (regardless of whether they are functional or nonfunctional).
- Train a classifier to discriminate targets from non-targets.
- Test the classifier.
- Use the classifier to sort unknown miRNA-mRNA interactions as positive (target) or negative (non-target).
2.1.3. Operative Strategy
3. miRNA Target Validation
3.1. Validation Methods
3.1.1. Criterion I: Show Co-Expression of miRNA and Target mRNA In Vivo
3.1.2. Criterion II: Prove Interaction between miRNA and a Specific mRE Target Site
3.1.3. Criterion III: Demonstrate miRNA-Mediated Effects on Target Protein Expression
3.1.4. Criterion IV: Demonstrate miRNA Effects on Biological Function
3.2. High-Throughput Technologies
3.2.1. Transcriptomic Analysis and Sequencing
- (1)
- (2)
- (3)
- These assays are time consuming and labour intensive.
- (4)
- Accessibility to mRE sites by miRNA may be very difficult when 3′-UTR sequence gives rise to a complicated secondary structure [84].
- (5)
- The choice of a cell culture as a suitable model to clearly detect consequences of miRNA mimic/inhibitor transfection is challenging: it should express appropriate amounts of endogenous miRNA and target gene.
3.2.2. Biochemical Assays
3.2.3. Proteomic Analysis
3.3. Strengths and Limitations
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Tool Name | SF | TS | EC | SA | Web | Ref. |
---|---|---|---|---|---|---|
miRanda | √ | √ | √ | http://www.microrna.org/microrna | [19] | |
TargetScan | √ | √ | √ | √ | http://www.targetscan.org/vert_72 | [29] |
RNAhybrid | √ | https://bibiserv.cebitec.uni-bielefeld.de/rnahybrid | [17] | |||
PITA | √ | √ | https://genie.weizmann.ac.il/pubs/mir07/mir07_prediction.html | [30] | ||
microTAR | √ | √ | http://tiger.dbs.nus.edu.sg/microtar | [16] | ||
PicTar | √ | √ | https://pictar.mdc-berlin.de | [27] | ||
PACMIT | √ | √ | √ | https://paccmit.epfl.ch | [31] | |
MIRZA-G | √ | √ | √ | √ | http://www.clipz.unibas.ch/index.php?r=tools/sub/mirza_g | [32] |
RNA22 | √ | √ | https://cm.jefferson.edu/rna22/Interactive | [33] |
Tool Name | Algorithm | Positive | Negative | Features | Ref. |
---|---|---|---|---|---|
MBSTar | Random Forest | MiRbase | Randomly generated | sequence, structure | [40] |
NbmiRTar | Naïve Bayes | TarBase | Probability Randomization | sequence | [41] |
TargetBoost | Genetic Programming | let-7, lin-4, miR-13a, bantam | Random string | sequence | [42] |
DeepTarget | RNN | miRecords miRBase | Mocking in alignment | sequence | [43] |
TargetMiner | SVM | miRecords | Randomly generated | seed | [44] |
DeepMirTar | Autoencoder | miRecords | Mocking in alignment | sequence, structure, energy and other | [45] |
DIANA-microT-CDS | microT-CDS algorithm | miRNA regulatory element in both the 3’-UTR and CDS | sequence, structure, energy and other | [46] | |
miRanda-mirSVR | SVR (similar to SVM) | set from transfection experiments | sequence, structure, energy and other | [47] |
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Riolo, G.; Cantara, S.; Marzocchi, C.; Ricci, C. miRNA Targets: From Prediction Tools to Experimental Validation. Methods Protoc. 2021, 4, 1. https://doi.org/10.3390/mps4010001
Riolo G, Cantara S, Marzocchi C, Ricci C. miRNA Targets: From Prediction Tools to Experimental Validation. Methods and Protocols. 2021; 4(1):1. https://doi.org/10.3390/mps4010001
Chicago/Turabian StyleRiolo, Giulia, Silvia Cantara, Carlotta Marzocchi, and Claudia Ricci. 2021. "miRNA Targets: From Prediction Tools to Experimental Validation" Methods and Protocols 4, no. 1: 1. https://doi.org/10.3390/mps4010001
APA StyleRiolo, G., Cantara, S., Marzocchi, C., & Ricci, C. (2021). miRNA Targets: From Prediction Tools to Experimental Validation. Methods and Protocols, 4(1), 1. https://doi.org/10.3390/mps4010001