Evaluation of network inference algorithms and their effects on network analysis for the study of small metabolomic data sets

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dc.contributor.author Greenyer, Haley
dc.date.accessioned 2022-05-24T23:46:19Z
dc.date.available 2022-05-24T23:46:19Z
dc.date.copyright 2022 en_US
dc.date.issued 2022-05-24
dc.identifier.uri http://hdl.handle.net/1828/13964
dc.description.abstract Motivation: Alzheimer’s Disease (AD) is a highly prevalent, neurodegenerative disease which causes gradual cognitive decline. As documented in the literature, evi- dence has recently mounted for the role of metabolic dysfunction in AD. Metabolomic data has therefore been increasingly used in AD studies. Metabolomic disease studies often suffer from small sample sizes and inflated false discovery rates. It is therefore of great importance to identify algorithms best suited for the inference of metabolic networks from small cohort disease studies. For future benchmarking, and for the development of new metabolic network inference methods, it is similarly important to identify appropriate performance measures for small sample sizes. Results: The performances of 13 different network inference algorithms, includ- ing correlation-based, regression-based, information theoretic, and hybrid methods, were assessed through benchmarking and structural network analyses. Benchmark- ing was performed on simulated data with known structures across six sample sizes using three different summative performance measures: area under the Receiver Op- erating Characteristic Curve, area under the Precision Recall Curve, and Matthews Correlation Coefficient. Structural analyses (commonly applied in disease studies), including betweenness, closeness, and eigenvector centrality were applied to simu- lated data. Differential network analysis was additionally applied to experimental AD data. Based on the performance measure benchmarking and network analysis results, I identified Probabilistic Context Likelihood Relatedness of Correlation with Biweight Midcorrelation (PCLRCb) (a novel variation of the PCLRC algorithm) to be best suited for the prediction of metabolic networks from small-cohort disease studies. Additionally, I identified Matthews Correlation Coefficient as the best mea- sure with which to evaluate the performance of metabolic network inference methods across small sample sizes. en_US
dc.language English eng
dc.language.iso en en_US
dc.rights Available to the World Wide Web en_US
dc.subject Alzheimer's en_US
dc.subject Metabolomics en_US
dc.subject Differential Network Analysis en_US
dc.subject sample size en_US
dc.subject network inference en_US
dc.subject mouse model en_US
dc.title Evaluation of network inference algorithms and their effects on network analysis for the study of small metabolomic data sets en_US
dc.type Thesis en_US
dc.contributor.supervisor Jabbari, Hosna
dc.contributor.supervisor Stege, Ulrike
dc.degree.department Department of Computer Science en_US
dc.degree.level Master of Science M.Sc. en_US
dc.description.scholarlevel Graduate en_US

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