The DNEA R package is the latest implementation of the Differential Network Enrichment Analysis algorithm and is the successor to the Filigree Java-application described in Iyer et al. (2020). The package is designed to take as input an m x n expression matrix for some -omics modality (ie. metabolomics, lipidomics, proteomics, etc.) and jointly estimate the biological network associations of each condition using the DNEA algorithm described in Ma et al. (2019). This approach provides a framework for data-driven enrichment analysis across two experimental conditions that utilizes the underlying correlation structure of the data to determine feature-feature interactions.