Abstract
Background: Transcriptome sequencing has been broadly available in clinical studies. However, it remains a challenge to utilize these data effectively to due to the high dimension of the data and the high correlation of gene expression. Methods: We propose a novel method that transforms RNA sequencing data into artificial image objects (AIOs) and apply convolutional neural network (CNN) algorithm to classify these AIOs. The AIO technique considers each gene as a pixel in digital image, standardizes and rescales gene expression levels into a range suitable for image display. Using the GSE81538 (n = 405) and GSE96058 (n = 3,373) datasets, we create AIOs for the subjects and design CNN models to classify biomarker Ki67 and Nottingham histologic grade (NHG). Results: With 5-fold cross validation, we accomplish a classification accuracy and AUC of 0.797 ± 0.034 and 0.820 ± 0.064 for Ki67 status. For NHG, the weighted average of categorical accuracy is 0.726 ± 0.018, and the weighted average of AUC is 0.848 ± 0.019. With GSE81538 as training data and GSE96058 as testing data, the accuracy and AUC for Ki67 are 0.772 ± 0.014 and 0.820 ± 0.006, and that for NHG are 0.682 ± 0.013 and 0.808 ± 0.003 respectively. These results are comparable to or better than the results reported in the original study. For both Ki67 and NHG, the calls from our models have similar predictive power for survival as the calls from trained pathologists in survival analyses. Comparing the calls from our models and the pathologists, we find that the discordant subjects for Ki67 are a group of patients for whom estrogen receptor, progesterone receptor, PAM50 and NHG could not predict their survival rate, and their responses to chemotherapy and endocrine therapy are also different from the concordant subjects. Conclusions: RNA sequencing data can be transformed into AIOs and be used to classify the status of Ki67 and NHG by CNN algorithm. The AIO method can handle high dimension data with highly correlated variables with no requirement for variable selection, leading to a data-driven, consistent and automation-ready approach to model RNA sequencing data.
Artificial image objects for classification of schizophrenia with GWAS-selected SNVs and convolutional neural network
