2dGBH: Two-dimensional group Benjamini–Hochberg procedure for false discovery rate control in two-way multiple testing of genomic data

Motivation: Emerging omics technologies have introduced a two-way grouping structure in multiple testing, as seen in single-cell omics data, where the features can be grouped by either genes or cell types. Traditional multiple testing methods have limited ability to exploit such two-way grouping structure, leading to potential power loss. Results: We propose a new 2D Group Benjamini–Hochberg (2dGBH) procedure to harness the two-way grouping structure in omics data, extending the traditional one-way adaptive GBH procedure. Using both simulated and real datasets, we show that 2dGBH effectively controls the false discovery rate across biologically relevant settings, and it is more powerful than the BH or q-value procedure and more robust than the one-way adaptive GBH procedure.