TargetScan - Pct value: What does it convey?

Question

[meetgirish1986]

Hi,

I am using TargetScan to identify conserved targets for miRNAs. I downloaded the file Predicted Conserved Targets which contains miR family, gene Id, gene symbol and other information along with Pct. Pct is the probability of conserved targeting. For eg. if we consider miR-210 and look up the targets for this miRNA in predicted conserved targets file, the following can be observed:

miR_Family    Gene_ID    Gene_Symbol    Transcript_ID    Species_ID    UTR_start    UTR_end    MSA_start MSA_end    Seed_match    PCT
miR-210    115    ADCY9    NM_001116    30611    476    482    711    721    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    10141    485    491    711    719    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    10116    500    506    711    719    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    10090    512    518    711    719    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    42254    343    349    715    721    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    9361    475    481    707    723    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    9615    492    498    711    719    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    9796    459    465    711    719    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    9913    422    428    711    719    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    9986    489    495    707    715    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    9986    497    503    717    723    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    9685    525    531    711    719    7mer-m8    0.24
miR-210    115    ADCY9    NM_001116    9785    482    488    711    721    7mer-m8    0.24

Last column is the probability value. In this case it is 0.24. Does this mean the probability of conservation of this target gene across the species is 0.24?

Answer 1

[Lars Juhl Jensen]

It is not completely clear to me what you mean by "the probability of conservation of this target gene across the species". Specifically, I'm not sure if you talk about conservation of the gene or conservation of it being a target, and also not clear across which species it would be conserved. But despite that, I think it is fair to say that the answer to your question is "No".

According to the TargetScan paper by Friedman et al. (2009), PCT is "the Bayesian estimate of the probability that a site is conserved due to selective maintenance of miRNA targeting rather than by chance or any other reason not pertinent to miRNA targeting". It is thus not the probability that the gene is conserved. And since a gene often has multiple binding sites for the same miRNA, it is also not the probability of it being conserved that the gene is a target of the miRNA. Rather it is the probability of the specific site being subject to selective pressure due to being a miRNA binding site. In other words, it is a score that uses evolutionary conservation to assess how like the site is to be a true target site.