title: Stress-induced changes in gene interactions in human cells.
abstract: Cells respond to variable environments by changing gene expression and gene interactions. To study how human cells response to stress, we analyzed the expression of >5000 genes in cultured B cells from nearly 100 normal individuals following endoplasmic reticulum stress and exposure to ionizing radiation. We identified thousands of genes that are induced or repressed. Then, we constructed coexpression networks and inferred interactions among genes. We used coexpression and machine learning analyses to study how genes interact with each other in response to stress. The results showed that for most genes, their interactions with each other are the same at baseline and in response to different stresses; however, a small set of genes acquired new interacting partners to engage in stress-specific responses. These genes with altered interacting partners are associated with diseases in which endoplasmic reticulum stress response or sensitivity to radiation has been implicated. Thus, our findings showed that to understand disease-specific pathways, it is important to identify not only genes that change expression levels but also those that alter interactions with other genes.
authors.affiliation: Medical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA, Division of Rheumatology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA, HHMI Medical Research Fellows Program, University of Pennsylvania, Philadelphia, PA 19104, USA, Department of Computer and Information Science, University of Pennsylvania, Philadelphia, PA 19104, USA, Department of Pediatrics, University of Pennsylvania, Philadelphia, PA 19104, USA, Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA and Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Renuka R
authors.initials: RR
authors.lastname: Nayak
authors.forename: William E
authors.initials: WE
authors.lastname: Bernal
authors.forename: Jessica W
authors.initials: JW
authors.lastname: Lee
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kearns
authors.forename: Vivian G
authors.initials: VG
authors.lastname: Cheung
mesh_terms: D001185:Artificial Intelligence; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D011839:Radiation, Ionizing; D013312:Stress, Physiological / Q000235:genetics*