Gene Expression Data Based Deep Learning Model for Accurate Prediction of Drug-Induced Liver Injury in Advance

Recently, large-scale bioinformatics and genomic data have been generated using advanced biotechnology methods, thus increasing the importance of analyzing such data. Numerous data mining methods have been developed to process genomic data in the field of bioinformatics. We extracted significant genes for the prognosis prediction of 1157 patients using gene expression data from patients with kidney cancer. We then proposed an end-to-end, cost-sensitive hybrid deep learning (COST-HDL) approach with a cost-sensitive loss function for classification tasks on imbalanced kidney cancer data. Here, we combined the deep symmetric auto encoder; the decoder is symmetric to the encoder in terms of layer structure, with reconstruction loss for non-linear feature extraction and neural network with balanced classification loss for prognosis prediction to address data imbalance problems. Combined clinical data from patients with kidney cancer and gene data were used to determine the optimal classification model and estimate classification accuracy by sample type, primary diagnosis, tumor stage, and vital status as risk factors representing the state of patients. Experimental results showed that the COST-HDL approach was more efficient with gene expression data for kidney cancer prognosis than other conventional machine learning and data mining techniques. These results could be applied to extract features from gene biomarkers for prognosis prediction of kidney cancer and prevention and early diagnosis.

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Deep Learning on High-Throughput Transcriptomics to Predict Drug-Induced Liver Injury

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2020.562677 ◽

2020 ◽

Vol 8 ◽

Author(s):

Ting Li ◽

Weida Tong ◽

Ruth Roberts ◽

Zhichao Liu ◽

Shraddha Thakkar

Keyword(s):

Deep Learning ◽

Liver Injury ◽

High Throughput ◽

Permutation Test ◽

Characteristic Curve ◽

Machine Learning Algorithms ◽

Attrition Rate ◽

Support Vector ◽

Drug Induced ◽

Drug Induced Liver Injury

Drug-induced liver injury (DILI) is one of the most cited reasons for the high drug attrition rate and drug withdrawal from the market. The accumulated large amount of high throughput transcriptomic profiles and advances in deep learning provide an unprecedented opportunity to improve the suboptimal performance of DILI prediction. In this study, we developed an eight-layer Deep Neural Network (DNN) model for DILI prediction using transcriptomic profiles of human cell lines (LINCS L1000 dataset) with the current largest binary DILI annotation data [i.e., DILI severity and toxicity (DILIst)]. The developed models were evaluated by Monte Carlo cross-validation (MCCV), permutation test, and an independent validation (IV) set. The developed DNN model achieved the area under the receiver operating characteristic curve (AUC) of 0.802 and 0.798, and balanced accuracy of 0.741 and 0.721 for training and an IV set, respectively, outperforming the conventional machine learning algorithms, including K-nearest neighbors (KNN), Support Vector Machine (SVM), and Random Forest (RF). Moreover, the developed DNN model provided a more balanced sensitivity of 0.839 and specificity of 0.603. Besides, we found the developed DNN model had a superior predictive performance for oncology drugs. Also, the functional and network analysis of genes driving the predictions revealed their relevance to the underlying mechanisms of DILI. The proposed DNN model could be a promising tool for early detection of DILI potential in the pre-clinical setting.

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