We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
RefDNN: a reference drug based neural network for more accurate prediction of anticancer drug resistance.
- Authors
Choi, Jonghwan; Park, Sanghyun; Ahn, Jaegyoon
- Abstract
Cancer is one of the most difficult diseases to treat owing to the drug resistance of tumour cells. Recent studies have revealed that drug responses are closely associated with genomic alterations in cancer cells. Numerous state-of-the-art machine learning models have been developed for prediction of drug responses using various genomic data and diverse drug molecular information, but those methods are ineffective to predict drug response to untrained drugs and gene expression patterns, which is known as the cold-start problem. In this study, we present a novel deep neural network model, termed RefDNN, for improved prediction of drug resistance and identification of biomarkers related to drug response. RefDNN exploits a collection of drugs, called reference drugs, to learn representations for a high-dimensional gene expression vector and a molecular structure vector of a drug and predicts drug response labels using the reference drug-based representations. These calculations come from the observation that similar chemicals have similar effects. The proposed model not only outperformed existing computational prediction models in most comparative experiments, but also showed more robust prediction for untrained drugs and cancer types than traditional machine learning models. RefDNN exploits the ElasticNet regularization to deal with high-dimensional gene expression data, which allows identification of gene markers associated with drug resistance. Lastly, we described an application of RefDNN in exploring a new candidate drug for liver cancer. As the proposed model can guarantee good prediction of drug responses to untrained drugs for given gene expression patterns, it may be of potential benefit in drug repositioning and personalized medicine.
- Subjects
CANCER treatment; ANTINEOPLASTIC agents; DRUG resistance; CANCER cells; GENE expression
- Publication
Scientific Reports, 2020, Vol 10, Issue 1, p1
- ISSN
2045-2322
- Publication type
Academic Journal
- DOI
10.1038/s41598-020-58821-x