Fuzzy-FishNet: A highly precise distribution-free network approach for feature selection in clinical proteomics

Network-based analysis methods can help resolve coverage and inconsistency issues in proteomics data. Previously, it was demonstrated that a suite of rank-based network approaches (RBNAs) provides unparalleled consistency and reliable feature selection. However, reliance on the t-statistic/t-distribution and hypersensitivity (coupled to a relatively flat p-value distribution) makes feature prioritization for validation difficult. To address these concerns, a refinement based on the fuzzified Fisher exact test, Fuzzy-FishNet was developed. Fuzzy-FishNet is highly precise (providing probability values that allows exact ranking of features). Furthermore, feature ranks are stable, even in small sample size scenario. Comparison of features selected by genomics and proteomics data respectively revealed that in spite of relative feature stability, cross-platform overlaps are extremely limited, suggesting that networks may not be the answer towards bridging the proteomics-genomics divide.