Abstract
Functional Gene Set Analysis Predicts Novel Cellular And Molecular Immune Mediators Of Impaired Diabetic Wound Healing
Wound repair and regeneration, v 25(4), pp A28-A28
Jul 2017
Abstract
Chronic diabetic ulcers remain an intractable clinical problem, in part because the underlying mechanisms of impaired diabetic wound healing are not yet fully understood. Gene expression profiling holds great potential in enhancing the understanding of pathophysiologic wound healing. The analysis of individual genes, however, is insensitive to detect signals that are subtle at the level of single genes but consistently distributed across a network of functionally related genes. Gene set analysis (GSA) is an alternative statistical method that instead focuses on differential expression of sets of biologically related genes, commonly referred to as gene sets. Gene sets are defined a priori based on biological knowledge and may include genes that either are members of the same pathway, have a common biological function, are coexpressed in response to certain stimuli, or share a binding motif. Given that the immune system is a key player in wound healing, we employed functional GSA—an extension of GSA to time-course data—to investigate differential variation of a large compendium of immune signature gene sets in a transcriptional study of impaired cutaneous wound healing in diabetic mice (Leprdb; db/db). Using publicly accessible data, over 5,000 sets of genes corresponding to various biological processes, cell states, and perturbations in the mouse immune system were obtained, and significant differential variation was assessed between diabetic and control mice for each set while taking into account the potential temporal heterogeneity of expression profiles. Although exploratory, we were able to recapitulate many known facts in immunology and diabetic wound healing, such as the temporal dynamic of the abundance of effector immune cells following injury. Importantly, we also implicated several previously undescribed immunological pathways in diabetic wound healing, demonstrating how public data repositories can be used for generating hypotheses, as well as predicting potential mechanisms of complex biological processes.
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Details
- Title
- Functional Gene Set Analysis Predicts Novel Cellular And Molecular Immune Mediators Of Impaired Diabetic Wound Healing
- Creators
- Sina Nassiri - Drexel University, School of Biomedical Engineering, Science, and Health SystemsE. A. Grice - Raymond and Ruth Perelman School of Medicine at the University of PennsylvaniaM. Palma - École Polytechnique Fédérale de LausanneK. Pourrezaei - Drexel University, School of Biomedical Engineering, Science, and Health SystemsI. Zakeri - Drexel University, Dana and David Dornsife School of Public Health
- Publication Details
- Wound repair and regeneration, v 25(4), pp A28-A28
- Conference
- San Diego, California, United States, 29th (29th Annual Meeting of the Wound Healing Society, SAWC-Spring/WHS Joint Meeting, 05 Apr 2017–09 Apr 2017)
- Publisher
- Hoboken, Wiley
- Number of pages
- 1
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Epidemiology and Biostatistics; College of Engineering
- Other Identifier
- 991019170124104721