Markus List

Summary Diseases can be caused by molecular perturbations that induce specific changes in regulatory interactions and their coordinated expression, also referred to as network rewiring. However, the detection of complex changes in regulatory connections remains a challenging task and would benefit from the development of novel nonparametric approaches. We develop a new ensemble method called BoostDiff (boosted differential regression trees) to infer a differential network discriminating between two conditions. BoostDiff builds an adaptively boosted (AdaBoost) ensemble of differential trees with respect to a target condition. To build the differential trees, we propose differential variance improvement as a novel splitting criterion. Variable importance measures derived from the resulting models are used to reflect changes in gene expression predictability and to build the output differential networks. BoostDiff outperforms existing differential network methods on simulated data evaluated in four different complexity settings. We then demonstrate the power of our approach when applied to real transcriptomics data in COVID-19, Crohn’s disease, breast cancer, prostate adenocarcinoma, and stress response in Bacillus subtilis. BoostDiff identifies context-specific networks that are enriched with genes of known disease-relevant pathways and complements standard differential expression analyses. Availability and implementation BoostDiff is available at https://github.com/scibiome/boostdiff_inference.

Summary Transcriptome deconvolution has emerged as a reliable technique to estimate cell-type abundances from bulk RNA sequencing data. Unlike their human equivalents, methods to quantify the cellular composition of complex tissues from murine transcriptomics are sparse and sometimes not easy to use. We extended the immunedeconv R package to facilitate the deconvolution of mouse transcriptomics, enabling the quantification of murine immune-cell types using 13 different methods. Through immunedeconv, we further offer the possibility of tweaking cell signatures used by deconvolution methods, providing custom annotations tailored for specific cell types and tissues. These developments strongly facilitate the study of the immune-cell composition of mouse models and further open new avenues in the investigation of the cellular composition of other tissues and organisms. Availability and implementation The R package and the documentation are available at https://github.com/omnideconv/immunedeconv.