JUMP: replicability analysis of high-throughput experiments with applications to spatial transcriptomic studies.

Abstract

Replicability is the cornerstone of scientific research. The current statistical method for high-dimensional replicability analysis either cannot control the false discovery rate (FDR) or is too conservative. We propose a statistical method, JUMP, for the high-dimensional replicability analysis of two studies. The input is a high-dimensional paired sequence of p-values from two studies and the test statistic is the maximum of p-values of the pair. JUMP uses four states of the p-value pairs to indicate whether they are null or non-null. Conditional on the hidden states, JUMP computes the cumulative distribution function of the maximum of p-values for each state to conservatively approximate the probability of rejection under the composite null of replicability. JUMP estimates unknown parameters and uses a step-up procedure to control FDR. By incorporating different states of composite null, JUMP achieves a substantial power gain over existing methods while controlling the FDR. Analyzing two pairs of spatially resolved transcriptomic datasets, JUMP makes biological discoveries that otherwise cannot be obtained by using existing methods. An R package JUMP implementing the JUMP method is available on CRAN (https://CRAN.R-project.org/package=JUMP).