Identification of potential tissue-specific cancer biomarkers and development of cancer versus normal genomic classifiers
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Akram Mohammed1, Greyson Biegert1, Jiri Adamec1 and Tomáš Helikar1
1Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
Tomáš Helikar, email: [email protected]
Keywords: cancer classification, biomarker identification, microarray gene expression, machine learning, cancer biomarker
Received: June 08, 2017 Accepted: September 05, 2017 Published: September 21, 2017
Machine learning techniques for cancer prediction and biomarker discovery can hasten cancer detection and significantly improve prognosis. Recent “OMICS” studies which include a variety of cancer and normal tissue samples along with machine learning approaches have the potential to further accelerate such discovery. To demonstrate this potential, 2,175 gene expression samples from nine tissue types were obtained to identify gene sets whose expression is characteristic of each cancer class. Using random forests classification and ten-fold cross-validation, we developed nine single-tissue classifiers, two multi-tissue cancer-versus-normal classifiers, and one multi-tissue normal classifier. Given a sample of a specified tissue type, the single-tissue models classified samples as cancer or normal with a testing accuracy between 85.29% and 100%. Given a sample of non-specific tissue type, the multi-tissue bi-class model classified the sample as cancer versus normal with a testing accuracy of 97.89%. Given a sample of non-specific tissue type, the multi-tissue multi-class model classified the sample as cancer versus normal and as a specific tissue type with a testing accuracy of 97.43%. Given a normal sample of any of the nine tissue types, the multi-tissue normal model classified the sample as a particular tissue type with a testing accuracy of 97.35%. The machine learning classifiers developed in this study identify potential cancer biomarkers with sensitivity and specificity that exceed those of existing biomarkers and pointed to pathways that are critical to tissue-specific tumor development. This study demonstrates the feasibility of predicting the tissue origin of carcinoma in the context of multiple cancer classes.
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