PON-mt-tRNA
PON-mt-tRNA is a posterior probability-based tool for classification of human mitochondrial tRNA (mt-tRNA) variations.
First it predicts the probability of pathogenicity using 20 machine learning (ML) predictors.
Then, it uses the predicted probability as prior probability and integrates with the evidence submitted by the user.
If no evidence is submitted, PON-mt-tRNA classifies the variations based on ML predicted probability.
The ML predictors utilize features representing evolutionary conservation, sequence context, secondary structure and tertiary interactions.
The method is trained by using variations that were classified previously by using evidence-based classification method by Yarham et al..
Balanced accuracy and Matthews correlation coefficient (MCC) for integrated classifier based on posterior probability are 0.99 and 0.95, respectively and for ML predictor based probability of pathogenicity are 0.81 and 0.56, respectively on independent test dataset.
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Submit queries to PON-mt-tRNA
mtDNA location and/or evidence
PON-mt-tRNA requires variation location, and the reference and altered nucleotides separated by comma.
In addition, the users can submit evidence of segregation, biochemical test and histochemical test which are optional.
The evidence should be submitted in the following manner:
| Evidence |
Result |
Input format |
| Segregation |
Segregation of variation with disease
No segregation with disease
Not available
|
1
0
NA |
| Biochemistry |
Biochemical defect in complexes I, III or IV
No biochemical defect in the complexes I, III and IV
Not available
|
1
0
NA |
| Histochemistry |
Histochemical evidence of mitochondrial disease
No histochemical evidence of mitochondrial disease
Not available
|
1
0
NA |
Note: The evidence should be submitted in the order Segregation, Biochemistry and Histochemistry. If evidence of Segregation is not known but others are known, NA should be used for segregation and then other should be provided.
Multiple variations can be submitted in a single query.
PON-mt-tRNA only classifies the single nucleotide substitutions and therefore does not accept other types of variations as input.
Alternatively, a file containing the variations in the same format as described above can be uploaded.
Example:
DNA location,Reference nucleotide,New nucleotide[,Segregation[,Biochemistry,[Histochemistry]]]
618,T,C
7505,A,G,1
8300,T,C,NA,1,NA
7316,T,C,0,NA,1
7316,T,A,0,NA,0
7316,T,C,1,1,1
7316,T,A,NA,NA,NA
7316,T,C,0,0,0
Email
Email field is obligatory. The predictions will be sent to you in the provided email address.
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