Clinical drug response prediction from preclinical cancer cell lines by logistic matrix factorization approach

Abstract

Predicting tumor drug response using cancer cell line drug response values for a large number of anti-cancer drugs is a significant challenge in personalized medicine. Predicting patient response to drugs from data obtained from preclinical models is made easier by the availability of different knowledge on cell lines and drugs. This paper proposes the TCLMF method, a predictive model for predicting drug response in tumor samples that was trained on preclinical samples and is based on the logistic matrix factorization approach. The TCLMF model is designed based on gene expression profiles, tissue type information, the chemical structure of drugs and drug sensitivity (IC 50) data from cancer cell lines. We use preclinical data from the Genomics of Drug Sensitivity in Cancer dataset (GDSC) to train the proposed drug response model, which we then use to predict drug sensitivity of samples from the Cancer Genome Atlas (TCGA) dataset. The TCLMF approach focuses on identifying successful features of cell lines and drugs in order to calculate the probability of the tumor samples being sensitive to drugs. The closest cell line neighbours for each tumor sample are calculated using a description of similarity between tumor samples and cell lines in this study. The drug response for a new tumor is then calculated by averaging the low-rank features obtained from its neighboring cell lines. We compare the results of the TCLMF model with the results of the previously proposed methods using two databases and two approaches to test the model’s performance. In the first approach, 12 drugs with enough known clinical drug response, considered in previous methods, are studied. For 7 drugs out of 12, the TCLMF can significantly distinguish between patients that are resistance to these drugs and the patients that are sensitive to them. These approaches are converted to classification models using a threshold in the second approach, and the results are compared. The results demonstrate that the TCLMF method provides accurate predictions across the results of the other algorithms. Finally, we accurately classify tumor tissue type using the latent vectors obtained from TCLMF’s logistic matrix factorization process. These findings demonstrate that the TCLMF approach produces effective latent vectors for tumor samples. The source code of the TCLMF method is available in https://github.com/emdadi/TCLMF.

Correlation of gene expression profiles to identify pancreatic cancer cell lines that best model primary human tumors

“…Several recent studies have compared the messenger RNA (mRNA) expression profiles of cell lines and primary tumors of various cancers ( 12 - 16 ); the genetic similarity between cell lines and primary tissues was found to be tumor dependent. Cell lines with moderately similar gene expression to primary tumors were reported to have a median correlation coefficient of 0.6 in the Cancer Cell Line Encyclopedia (CCLE) project ( 15 ).…”