DysRegNet: Patient-specific and confounder-aware dysregulated network inference

Gene regulation is frequently altered in diseases in unique and patient-specific ways. Hence, personalized strategies have been proposed to infer patient-specific gene-regulatory networks. However, existing methods do not scale well as they often require recomputing the entire network per sample. Moreover, they do not account for clinically important confounding factors such as age, sex, or treatment history. Finally, a user-friendly implementation for the analysis and interpretation of such net-works is missing. We present DysRegNet, a method for inferring patient-specific regulatory alterations (dysregulations) from bulk gene expression profiles. We compared DysRegNet to SSN, a well-known sample-specific network approach. We demonstrate that both SSN and DysRegNet produce interpretable and biologically meaningful networks across various cancer types. In contrast to SSN, DysRegNet can scale to arbitrary sample numbers and highlights the importance of confounders in network inference, revealing an age-specific bias in gene regulation in breast cancer. DysRegNet is available as a Python package (https://github.com/biomedbigdata/DysRegNet_package), and analysis results for eleven TCGA cancer types are available through an interactive web interface (https://exbio.wzw.tum.de/dysregnet).