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Efficient Gaussian sample specific network marker discovery and drug enrichment analysis validation
Institution:1. Institute of Computational Science and Technology, Guangzhou University, Guangzhou, 510006, China;2. Department of Physics and Electronic information engineering, Wenzhou University, Wenzhou, 325000, Zhejiang, China;3. College of Information engineering, Wenzhou Vocational & Technology College, Wenzhou, 325000, Zhejiang, China;4. Department of Computer and Information Science, Fordham University, New York, NY, 10023, USA;1. Institute of Biomechanics, TUHH Hamburg University of Technology, Hamburg, Germany;2. Department of Life Sciences, Hamburg University of Applied Sciences, Hamburg, Germany;3. Department of Orthopaedic and Trauma Surgery, University of Heidelberg, Heidelberg, Germany;4. Institute of Legal Medicine, University of Hamburg-Eppendorf, Hamburg, Germany;1. Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria;2. National Specialized Hospital for Active Treating of Haematological Diseases, Sofia, Bulgaria;1. University of Bradford, UK;2. University of Leeds, UK;1. Centre for Advanced Studies in Plant Biotechnology and Genetic Engineering, Department of Biosciences, Saurashtra University, Rajkot 360005, Gujarat, India;2. Agricultural Research Station, Ummedganj, Kota 324001. Rajasthan, India;3. DST-Centre for Policy Research, Entrepreneurship Development Institute of India, P.O. Bhat 382428. Gandhinagar, Gujarat, India;4. College of Agriculture, Sri Karan Narendra Agriculture University, Jobner, Jaipur, Rajasthan, India
Abstract:Identifying stable gene markers at an individual level can help to understand the genetic mechanisms of each individual patient and accomplish personalized medicine. In this paper, we propose an efficient framework to identify sample-specific markers. Gene expression data first is transformed to a corresponding likelihood matrix to alleviate inherent noise besides adding population information to each sample. Then those significantly differential genes or gene pairs are further mapped to a STRING network for analysis by assuming that the likelihood of each gene or gene pairs in the control group follows a Gaussian distribution. The proposed method is applied to three benchmark datasets including lung adenocarcinoma, kidney renal clear cell carcinoma, and uterine corpus endometrial carcinoma. It is found that disease gene markers identified by the proposed methods outperform the previous sample-specific network (SSN) method in both subtyping and survival analysis. Furthermore, we exploit the application of the subtype markers in following drug selection. The difference of the enriched drug set may reflect some underlying mechanisms of the subtypes and shed light on selecting appropriate drugs for each cancer subtype.
Keywords:Network biomarkers  Gaussian distribution  Cancer  Drug
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