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subsets [2016/12/27 21:44]
rkiss
subsets [2016/12/27 22:23] (current)
rkiss
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 ==== Property based filtering ==== ==== Property based filtering ====
  
-For the drug-like and fragment subsets the [[http://​www.sciencedirect.com/​science/​article/​pii/​S0169409X00001290|rule-of-5]] and [[http://​www.sciencedirect.com/​science/​article/​pii/​S1359644603028319|rule-of-3]] physicochemical property filters are applied allowing max 1 violation. Additionally,​ we used a few more rules:+For the drug-like and fragment subsets the [[http://​www.sciencedirect.com/​science/​article/​pii/​S0169409X00001290|rule-of-5]] and [[http://​www.sciencedirect.com/​science/​article/​pii/​S1359644603028319|rule-of-3]] physicochemical property filters are applied allowing max 1 violation. Additionally,​ we applied the following filtering criteria to skip some rather "​strange"​ compounds: 
   * number of components < = 1   * number of components < = 1
   * MW > = 100   * MW > = 100
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   * number of halogens < = 7   * number of halogens < = 7
   * number of inorganic atoms = 0   * number of inorganic atoms = 0
- 
-We used these rules to leave out more "​strange compounds"​ which may be included more likely in the diverse sets as they differ from the regular compounds. 
  
 ==== Diversity selection ==== ==== Diversity selection ====
  
-The Mcule database contains ~5.7M stock compounds and ~30.3M virtual compounds. ​Diversity selection was carried out in a way to prefer ​the stock compounds over the virtual ones. As a result, the chemical space is represented by stock compounds where possible. More over, the downloadable files contains the compounds in diversity order i.e. the first N compounds represent the most dissimilar N compounds, so you can choose yourself the number of compounds to represent the whole Ro3 and Ro5 subsets. +Diversity selection was set up to prefer ​in-stock compounds over virtual ones. As a result, the chemical space is represented by in-stock compounds where possible.
- +
-Structural similarity was measured by Tanimoto coefficient (TC) between FP2 linear fingerprints generated by OpenBabel. The combinations of the following algorithms were applied to extract the most dissimilar subsets: +
-  * we used sphere exclusion to eliminate highly similar compounds to reduce the input size where needed +
-  * then [[diversitysel|stepwise elimination]] was applied to obtain the most dissimilar compounds +
- +
-In sphere exclusion we used the stock compounds first as "​centers"​ for the elimination of redundant compounds, and we retained the stock compounds during the stepwise elimination.+
  
-===== Subsets =====+The [[https://​mcule.com/​database/​|downloadable files]] contain the compounds in diversity order i.e. the first N compounds represent the most dissimilar N compounds. This means that if you want to further narrow down the number of compounds you can keep the first X compounds of the files and they will be the most dissimilar ones.
  
-To speed up the selection, we used sphere exclusion in case of the Ro5 subsets with TC=0.to pass at most 3M compounds for stepwise elminiation. Then, the following subsets were saved:+Structural similarity was measured by Tanimoto coefficient (TC) between FP2 linear fingerprints generated by [[http://​jcheminf.springeropen.com/​articles/​10.1186/​1758-2946-3-33|OpenBabel]]. The combinations of the following algorithms were applied ​to extract the most dissimilar ​compounds
 +  * sphere exclusion: to quickly eliminate highly similar compounds to reduce the input collection to a manageable size for the subsequent [[diversitysel|stepwise elimination]] algorithm 
 +  * [[diversitysel|stepwise elimination]]a more thorough algorithm that eliminates one molecule of the most similar molecule pairs
  
-^Subset name ^Input ^Property filter ^Diversity ^Subset size ^ +In sphere exclusion we used the in-stock compounds ​first as "​centers"​ and eliminated their most similar analogswhile during [[diversitysel|stepwise elimination]] we retained the in-stock compounds ​from the most similar molecule pairs.
-|Mcule Purchasable (In Stock Ro5 Diverse 1M) |Stock compounds|rule-of-5, max 1 violation|top diverse 1M, max TC: 0.8|1,​000,​000| +
-|Mcule Purchasable (In Stock Ro5 Diverse 350K)|Stock ​compounds|rule-of-5 (max 1 violation)|Top diverse 350Kmax TC:0.7|350,000| +
-|Mcule Purchasable (In Stock Ro3)|Stock compounds|rule-of-3 (max 1 violation)|-|154,​238| +
-|Mcule Purchasable (In Stock Ro3 Diverse 50K)|Stock ​compounds|rule-of-3 (max 1 violation)|Top diverse 50K, max TC: 0.8|50,000| +
-|Mcule Purchasable (In Stock & Virtual Ro3)|Stock compounds + virtual compounds|rule-of-3 (max 1 violation)|-|789,​907| +
-|Mcule Purchasable (In Stock & Virtual Ro3 Diverse 70K)|Stock compounds + virtual compounds|rule-of-3 (max 1 violation)|Top diverse 70K, max TC: 0.8|70,000|+
  
 +Sphere exclusion diversity selection was applied in case of the rule-of-5 subsets with maximum TC=0.8 and a maximum of 3M compounds that were subjected to stepwise elimination.
subsets.1482871494.txt.gz · Last modified: 2016/12/27 21:44 by rkiss