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Description: BACKGROUND Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. Currently, a major problem in biology is to cherry pick the combinations based on expert advice, literature survey or guesses for investigation. The search and wet lab testing of these combinations costs a lot in terms of time, investment and energy. In a recent development of the PORCN-WNT inhibitor ETC-1922159 for colorectal cancer, a list of down-regulated genes were recorded in a time buffer after the administration of the drug. The regulation of the genes were recorded individually but for a majority, it is still not known which higher (≥ 2) order combinations might be playing a greater role in the pathway. RESULTS The pipeline provides a prioritised list of important 2nd order combinations of a range of family of genes involved in the Wnt pathway. More specifically, it reveals the various unexplored FZD-WNT combinations that have been untested till now in the pathway. In relation to ETC-1922159 affected combinations, the down-regulation of LGR-RNF family after the drug treatment is evident in these rankings as it takes bottom priorities for LGR5-RNF43 combination. The LGR6-RNF43 takes higher ranking than LGR5-RNF43, indicating that it might not be playing a greater role as LGR5 during the Wnt enhancing signals. These rankings confirm the efficacy of the proposed search engine design. CONCLUSION A pipeline has been developed to prioritise an nth order combination of factors that affect a signaling pathway. It takes into account the sensitivity indices computed from variance based (SOBOL) and density-kernel based (HSIC) methods to estimate the influence of each factor or combination of factors. These are then fed as feature vectors into a powerful support vector ranking algorithm that produces a ranked list of the interactions/combinations.