Training set inactives commonly featured carboxylic acids, N,N'-disubstituted ureas, secondary and tertiary amides, pyrazoles, aromatic sulfonamides, tertiary cyclopentanols, 1,2-mercaptoethanol, and penams.
This contribution of the inactive training samples may have a bigger impact in the PDGFRβ experiment than in the others, because all kernels regard a much higher proportion of the ligands as outliers than in the other screening experiments (i.e., the decoys might be more similar to the training set (inactives) than the ligands).
Inactive stimuli may display a mean p-value less than 0.05 and a negative Q-value whereas dominant stimuli display p-values less than 0.05 and positive Q-values (the other stimuli were set as inactive).
The descriptor rankings were produces using the p-value from a Kolmogorov-Smirnov test (KS-test) for significant difference between two data sets (inactive vs. active compounds), separately for each ORN.
Obviously, when all initial states of the network are set to zero (inactive or not available), the whole system will remain inactive.
INITIALIZATION: p = 0, τ 0 = 2 max i ( A T r ^ ) i, n = 0. J = active set = ∅, I = inactive set = J c. while ≠ stopping criterion and ∃ i ∈ I such that b i > 0 do 1) Compute the residual correlation b = A T ( r ^ - A p ) 2) Determine the maximal components of b.
9000 randomly selected ChEMBL molecules are added to the original test set as putative inactives.
All classifiers were able to correctly indicate active molecules, regardless of the changes in the inactives set composition, which is shown by the dark-red maps referring to this evaluating parameter.
What is also worth noting, the evaluating parameters values were much higher when molecules for inactives set formation were picked up randomly, rather than with the assurance of the maximum diversity of the selected compounds.
Two methods least affected by inactives set formation were Hyperpipes (SD < 0.1), and Ibk (SD equal 0.2 at most), yet the first one was at the same time the worst classifier in terms of MCC (MCC of 0.1 using ExtFP for molecules representation).
Table 2 Summary of the sizes of data sets of 208 activity classes, including known actives and inactives Diversity index Query set Reference set Test set Active Inactive Active Inactive Average 6.74 144 182 200 7380 29,154 Std 1.67 202 268 278 1.6784 72,1.67
