Individual elements that constitute the immune system have been characterized over the few past decades, mostly through reductionist approaches. The introduction of large-scale profiling platforms has more recently facilitated the assessment of these elements on a global scale. However, the analysis and the interpretation of such large-scale datasets remains a challenge and a barrier for the wider adoption of systems approaches in immunological and clinical studies. In this Innovation article, we describe an analytical strategy that relies on the a priori determination of co-dependent gene sets for a given biological system. Such modular transcriptional repertoires can in turn be used to simplify the analysis and the interpretation of large-scale datasets, and to design targeted immune fingerprinting assays and web applications that will further facilitate the dissemination of systems approaches in immunology.