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gioamendola authored Nov 30, 2021
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Expand Up @@ -63,7 +63,7 @@ Poor performance may be the result of several factors, which include:

The above cases and others are discussed in the [JCIM article](https://pubs.acs.org/doi/abs/10.1021/acs.jcim.1c00653). Importantly, adjusting the epsilon cutoff values may readily improve poor performance, especially with regards to TPR, FPR, Precision, and F-Score, as they impact the classification thresholds. The default cutoff values for both the active training set and the inactive training set is 0.95, so that 95% of the training set will be considered in the model building step. This allows to account for some tolerance to the presence/absence of chemical motifs. Higher values (e.g. closer to 1) for the active training cutoff generally result in more true positives and false positives alike. Instead, a higher cutoff for the inactive set fitting should mainly decrease the false positive rate with some effect on the TPR.

We suggest benchmarking using the possible combinations of **the following epsilon cutoff values: 0.84–0.95–0.98 for epsilon_active and 0.7–0.84–0.95–0.98 for epsilon_cutoff_inactive** and identify the combination with the best TPR/FPR tradeoff. Further information about the epsilon cutoff values are available in the [JCIM article](https://pubs.acs.org/doi/abs/10.1021/acs.jcim.1c00653) and in its Supporting Information PDF.
As a possible starting point, we suggest benchmarking using the possible combinations of **the following epsilon cutoff values: 0.84–0.95–0.98 for epsilon_active and 0.7–0.84–0.95–0.98 for epsilon_cutoff_inactive** and identify the combination with the best TPR/FPR tradeoff. Further information about the epsilon cutoff values are available in the [JCIM article](https://pubs.acs.org/doi/abs/10.1021/acs.jcim.1c00653) and in its Supporting Information PDF.

# RMD Algorithm
PyRMD implements the Random Matrix Discriminant (RMD) algorithm devised by [Lee et al.](https://www.pnas.org/content/116/9/3373) to identify small molecules endowed with biological activity. Parts of the RMD algorithm code were adapted from the [MATLAB version of the RMD](https://github.com/alphaleegroup/RandomMatrixDiscriminant) and a [Python implementation proposed by Laksh Aithani](https://towardsdatascience.com/random-matrix-theory-the-best-classifier-for-prediction-of-drug-binding-f82613fb48ed) of the [Random Matrix Theory](https://www.pnas.org/content/113/48/13564).

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