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. 2016 Dec 22;2:16037. doi: 10.1038/npjsba.2016.37

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Copyright © 2016 The Author(s)

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

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Calculation of gene state frequencies in patients of a given combination and across combinations. The frequencies of gene A in states of 'high' and 'low' expression in the subset of patients are defined by the expression profile of a given combination. These 'high' or 'low' values are assigned when the expression levels are respectively above or below the median of the expression for this gene in the entire population of patients. Once this frequency has been calculated for each of the selected combinations of genes, the average value of these frequencies across combinations are used as weights to sample a new set of combinations. Those gene states with higher average values across combinations have a better chance to be selected in the new set of combinations generated in the next iteration of the algorithm.