Evaluation of the Effectiveness of Herbal Components Based on Their Regulatory Signature on Carcinogenic Cancer Cells

Abstract

Predicting cancer cells’ response to a plant-derived agent is critical for the drug discovery process. Recently transcriptomes advancements have provided an opportunity to identify regulatory signatures to predict drug activity. Here in this study, a combination of meta-analysis and machine learning models have been used to determine regulatory signatures focusing on differentially expressed transcription factors (TFs) of herbal components on cancer cells. In order to increase the size of the dataset, six datasets were combined in a meta-analysis from studies that had evaluated the gene expression in cancer cell lines before and after herbal extract treatments. Then, categorical feature analysis based on the machine learning methods was applied to examine transcription factors in order to find the best signature/pattern capable of discriminating between control and treated groups. It was found that this integrative approach could recognize the combination of TFs as predictive biomarkers. It was observed that the random forest (RF) model produced the best combination rules, including AIP/TFE3/VGLL4/ID1 and AIP/ZNF7/DXO with the highest modulating capacity. As the RF algorithm combines the output of many trees to set up an ultimate model, its predictive rules are more accurate and reproducible than other trees. The discovered regulatory signature suggests an effective procedure to figure out the efficacy of investigational herbal compounds on particular cells in the drug discovery process.

Cutting-Edge Methods for Better Understanding Cells

“…Esmaeili et al performed a meta-analysis of six published bulk RNA sequencing (RNA-seq) data, and implemented three types of machine learning algorithms to identify potentially key transcription factors (TFs) to be regulated using herbal compounds in cancer cells. Using this approach, they identified four TFs, including AIP , VGLL4 , TFE3 and ID1, to be differentially expressed with the treatment of genistein, an isoflavone compound found in soy products and in liver cancer HepG2 cells [ 7 ].…”