Integrating personalized gene expression profiles into predictive disease-associated gene pools
Year: 2017
Type: article
Abstract: 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 broadpool 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 framework 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.
Institutions: Northeastern University, Austrian Academy of Sciences, Central European University, CeMM Research Center for Molecular Medicine, Central European University - Budapest Campus, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard University, Janssen Research & Development (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,490
Awards: G1487879497, G2470583414, G3681705081, G4876354037, The Asthma BioRepository for Integrative Genomics Research, Center for Integrated Approached to Undiagnosed Diseases, Network Medicine - An interactome-based approach to rare diseases, A human binary interactome reference map by 2020, G7869672655, The Phathophenotype Landscape of Complex Disease, G794209665, Genomic Analysis of Network Perturbations in Human Disease, G8178563453, GPx-3 and Peroxide Flux in the Endothelial Cell, G9000055186, G9000056548, G9000154243, G9000263371, G9000339954
OpenAlex ID: W2592063047