Published in Nature: NJP Systems Biology and Applications

Authors: Jörg Menche, Emre Guney, Amitabh Sharma, Patrick J. Branigan, Matthew J. Loza, Frédéric Baribaud, Radu Dobrin & Albert-László Barábasi

npj Systems Biology and Applications (2017) 3:10 ; doi:10.1038/s41540-017-0009-0

Gene expression data are routinely used to identify genes that on average exhibit different expression levels between a case and a control group. Yet, very few of such differentially expressed genes are detectably perturbed in individual patients. Here, we develop a framework to construct personalized perturbation profiles for individual subjects, identifying the set of genes that are significantly perturbed in each individual. This allows us to characterize the heterogeneity of the molecular manifestations of complex diseases by quantifying the expression-level similarities and differences among patients with the same phenotype. We show that despite the high heterogeneity of the individual perturbation profiles, patients with asthma, Parkinson and Huntington’s disease share a broad pool of sporadically disease-associated genes, and that individuals with statistically significant overlap with this pool have a 80–100% chance of being diagnosed with the disease. The developed framaework opens up the possibility to apply gene expression data in the context of precision medicine, with important implications for biomarker identification, drug development, diagnosis and treatment.