NetTDP: permutation-based true discovery proportions for differential co-expression network analysis.

Existing methods for differential network analysis could only infer whether two networks of interest have differences between two groups of samples, but could not quantify and localize network differences. In this work, a novel method, permutation-based Network True Discovery Proportions (NetTDP), is proposed to quantify the number of edges (correlations) or nodes (genes) for which the co-expression networks are different. In the NetTDP method, we propose an edge-level statistic and a node-level statistic, and detect true discoveries of edges and nodes in the sense of differential co-expression network, respectively, by the permutation-based sumSome method. Furthermore, the NetTDP method could further localize the differences by inferring the TDPs for edge or gene subsets of interest, which can be selected post hoc. Our NetTDP method allows inference on data-driven modules or biology-driven gene sets, and remains valid even when these sub-networks are optimized using the same data. Experimental results on both simulation data sets and five real data sets show the effectiveness of the proposed method in inferring the quantification and localization of differential co-expression networks. The R code is available at https://github.com/LiminLi-xjtu/NetTDP.

Post-selection Inference in Multiverse Analysis (PIMA): An Inferential Framework Based on the Sign Flipping Score Test.

When analyzing data, researchers make some choices that are either arbitrary, based on subjective beliefs about the data-generating process, or for which equally justifiable alternative choices could have been made. This wide range of data-analytic choices can be abused and has been one of the underlying causes of the replication crisis in several fields. Recently, the introduction of multiverse analysis provides researchers with a method to evaluate the stability of the results across reasonable choices that could be made when analyzing data. Multiverse analysis is confined to a descriptive role, lacking a proper and comprehensive inferential procedure. Recently, specification curve analysis adds an inferential procedure to multiverse analysis, but this approach is limited to simple cases related to the linear model, and only allows researchers to infer whether at least one specification rejects the null hypothesis, but not which specifications should be selected. In this paper, we present a Post-selection Inference approach to Multiverse Analysis (PIMA) which is a flexible and general inferential approach that considers for all possible models, i.e., the multiverse of reasonable analyses. The approach allows for a wide range of data specifications (i.e., preprocessing) and any generalized linear model; it allows testing the null hypothesis that a given predictor is not associated with the outcome, by combining information from all reasonable models of multiverse analysis, and provides strong control of the family-wise error rate allowing researchers to claim that the null hypothesis can be rejected for any specification that shows a significant effect. The inferential proposal is based on a conditional resampling procedure. We formally prove that the Type I error rate is controlled, and compute the statistical power of the test through a simulation study. Finally, we apply the PIMA procedure to the analysis of a real dataset on the self-reported hesitancy for the COronaVIrus Disease 2019 (COVID-19) vaccine before and after the 2020 lockdown in Italy. We conclude with practical recommendations to be considered when implementing the proposed procedure.