Activity-enriched subsets

The bacterial strains were submitted to the National Collection of Microorganism Cultures of the Pasteur Institute (CNCM) and included R. erythropolis CNCM 1-2204, -2205, -2207, and -2208, and/or R. rhodnii 1-2206. The activity of the microorganisms includes a selective attack on the carbon-sulfur bonds in the organic molecules without significant alteration of the carbon atom structure. As usual, strains were isolated and subjected to successive enrichment phases, in media containing various sources of carbon and DBT as the only sulfur source, then a purification of the enhanced culture led to the fifteen DBT specific strains. From those strains, a subset of ten strains was selected... 

The confirmation rates for the selected set at different primary and confirmation percent inhibition thresholds appear in Table 6.2. Also shown are confirmation rates for those subsets of the selected that appear in the Top X selection either before or after filtering, which is the union of the selected set and the respective Top 4000 selections. The confirmation rate holds remarkably steady for all three sets at the four different thresholds for the primary inhibition examined if the threshold used to define confirmed actives is kept constant at 30%. If the confirmation threshold is instead increased along with the primary threshold, the confirmation rate drops for all three sets, which might be considered counterintuitive. However, this can be explained by the twin influences of edge effects (Section 6.1.5) and the enrichment of false positives at higher activities. This behavior has been reported previously by Fay and Ullmann [31] for both real... 

Once descriptors have been calculated for all compounds, the question arises as to which similarity metric is to be used to obtain maximal enrichment of actives in the library subset [42], Several comparative studies have revealed that there is no single best similarity metric that outperforms all others [37,40,42-44], Nevertheless,... 

If the virtual screening process is successful, the bioactive compounds will be enriched in the upper part of this ranked list. Enriched means that there are more active compounds in this part of the list than that one would expect based on the average content of bioactive compounds in the searched database. This enrichment can be determined only in retrospective studies where both the active and the inactive compounds in the database are known The emichment factor is typically used in such studies as a quality criterion for a particular virtual screening approach. Since the emichment factor depends on the chosen subset of the ranked list, it is common to calculate enrichment curves where the cumulated number of hits is plotted against the ranked list of compounds in the search database. In recent years, more and more researchers prefer other types of enrichment plots (e.g., ROC curves). The interested... 

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