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dc.contributor.authorPyman, Blakeen
dc.date.accessioned2018-12-05T19:01:03Z
dc.date.available2018-12-05T19:01:03Z
dc.identifier.urihttp://hdl.handle.net/1974/25856
dc.description.abstractBackground: MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression. Differential expression observed in miRNAs, combined with advancements in deep learning (DL), have the potential to improve cancer classification by modelling non-linear miRNA-phenotype associations. We propose a novel miRNA-based deep cancer classifier (DCC) incorporating genomic and hierarchical tissue annotation, capable of accurately predicting the presence of cancer in wide range of human tissues. Methods: miRNA expression profiles were analyzed for 2530 neoplastic and 5184 non-neoplastic samples, across 38 organ types involving 78 organ sub-structures and 173 cell types. Specificity of miRNA expression was explored in relation to tissue type and neoplasticity, adjusting for sampling bias using three levels of hierarchical annotation. A DL architecture composed of stacked autoencoders (AE) and a multi-layer perceptron (MLP) was trained to predict neoplasticity using 845 high-confidence miRNAs. Additional DCCs were trained using expression of miRNA cistrons and sequence families, and combined as a diagnostic ensemble. Predictive importance of miRNAs was measured using backpropagation, and top miRNAs analyzed in Cytoscape using iCTNet and BiNGO. Results: Performance of the DCC was tested on an unseen, randomly selected set of 1511 samples. The model classified cancer with 94.73% accuracy, 98.6% AUC/ROC, 95.1% sensitivity, and 94.3% specificity. A concise assay of the 20 most predictive miRNAs achieved 85.0% accuracy, 93.3% AUC/ROC, 92.3% sensitivity and 74.9% specificity. Conclusion: Deep autoencoder networks are a powerful tool for modelling complex miRNA-phenotype associations in cancer. The proposed DCC improves classification accuracy by learning from the biological context of both samples and miRNAs, using genomic and anatomic annotation. Analyzing the trained DCC also provides estimates of miRNAs importance for cancer prediction, which can be used for feature selection and biological discovery, by performing gene ontology searches on the most highly significant features.en
dc.language.isoengen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canadaen
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreementen
dc.rightsIntellectual Property Guidelines at Queen's Universityen
dc.rightsCopying and Preserving Your Thesisen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.rightsAttribution-NonCommercial 3.0 United Statesen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/
dc.subjectArtificial Intelligenceen
dc.subjectDeep learningen
dc.subjectmiRNAen
dc.subjectCancer diagnosisen
dc.subjectBioinformaticsen
dc.subjectTranscriptomicsen
dc.titleDeep Cancer Classifier: Exploring microRNA Regulation of Cancer with Deep Learningen
dc.typethesisen
dc.description.degreeM.Sc.en
dc.contributor.supervisorMousavi, Parvinen
dc.contributor.departmentComputingen
dc.degree.grantorQueen's University at Kingstonen


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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
Except where otherwise noted, this item's license is described as Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada