Entropic Ranks: A Methodology for Enhanced, Threshold-Free, Information-Rich Data Partition and Interpretation

Abstract

Background: Here, we propose a threshold-free selection method for the identification of differentially expressed features based on robust, non-parametric statistics, ensuring independence from the statistical distribution properties and broad applicability. Such methods could adapt to different initial data distributions, contrary to statistical techniques, based on fixed thresholds. This work aims to propose a methodology, which automates and standardizes the statistical selection, through the utilization of established measures like that of entropy, already used in information retrieval from large biomedical datasets, thus departing from classical fixed-threshold based methods, relying in arbitrary p-value and fold change values as selection criteria, whose efficacy also depends on degree of conformity to parametric distributions,. Methods: Our work extends the rank product (RP) methodology with a neutral selection method of high information-extraction capacity. We introduce the calculation of the RP entropy of the distribution, to isolate the features of interest by their contribution to its information content. Goal is a methodology of threshold-free identification of the differentially expressed features, which are highly informative about the phenomenon under study. Conclusions: Applying the proposed method on microarray (transcriptomic and DNA methylation) and RNAseq count data of varying sizes and noise presence, we observe robust convergence for the different parameterizations to stable cutoff points. Functional analysis through BioInfoMiner and EnrichR was used to evaluate the information potency of the resulting feature lists. Overall, the derived functional terms provide a systemic description highly compatible with the results of traditional statistical hypothesis testing techniques. The methodology behaves consistently across different data types. The feature lists are compact and rich in information, indicating phenotypic aspects specific to the tissue and biological phenomenon investigated. Selection by information content measures efficiently addresses problems, emerging from arbitrary thresh-holding, thus facilitating the full automation of the analysis.