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WHAT THIS STUDY ADDS TO OUR KNOWLEDGE ☑ Compared to the conceptual PK model, the proposed PopPK model is a simplified but valid model that passed stringent validation processes.
However, proper preclinical work and stringent validation are needed before taking forward biomarkers into confirmatory studies.
In this article, we discuss how errors in these models arise and how they can be evaluated, and we argue for even more stringent validation checks and documentation of structures before deposition with the Protein Data Bank.
The workflow is greatly simplified for clarity and therefore the model should not be used without stringent validation.
However, if one takes into account the much stringent validation criteria imposed in our work (vs the cross-validation procedures employed in [13 21]) it is clear that the 3D-QSDAR methodology performs at least on par with these earlier models.
We then performed a more stringent validation using in situ hybridization.
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Due to high data completion rates and stringent data validation protocols by the AOA NJRR, the data are robust and easily lend themselves to this type of analysis.
Similarly, we generated a prediction map from each of these models and calculated both the mean prediction and corresponding 95% confidence intervals for each pixel and analysed prediction accuracy using the same stringent cross validation and sensitivity analysis procedure as for the bat distribution models (detailed above).
Stringent cross-validation schemes outperform LOO-CV.
LOO-CV again yielded relatively poor prediction errors and selected low numbers of k nearest neighbours as compared to the more stringent cross-validation schemes due to overfitting tendencies.
Fang et al. showed the regulatory capacity of jak1 based on standard differential expression analysis followed by stringent experimental validations [ 28].
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