Identification of drug combinations on the basis of machine learning to maximize anti-aging effects.

Journal: PloS one
PMID:

Abstract

Aging is a multifactorial process that involves numerous genetic changes, so identifying anti-aging agents is quite challenging. Age-associated genetic factors must be better understood to search appropriately for anti-aging agents. We utilized an aging-related gene expression pattern-trained machine learning system that can implement reversible changes in aging by linking combinatory drugs. In silico gene expression pattern-based drug repositioning strategies, such as connectivity map, have been developed as a method for unique drug discovery. However, these strategies have limitations such as lists that differ for input and drug-inducing genes or constraints to compare experimental cell lines to target diseases. To address this issue and improve the prediction success rate, we modified the original version of expression profiles with a stepwise-filtered method. We utilized a machine learning system called deep-neural network (DNN). Here we report that combinational drug pairs using differential expressed genes (DEG) had a more enhanced anti-aging effect compared with single independent treatments on leukemia cells. This study shows potential drug combinations to retard the effects of aging with higher efficacy using innovative machine learning techniques.

Authors

  • Sun Kyung Kim
    College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
  • Peter C Goughnour
    College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
  • Eui Jin Lee
    College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
  • Myeong Hyun Kim
    Center for Research and Development, Oncocross Ltd., Seoul, Republic of Korea.
  • Hee Jin Chae
    Center for Research and Development, Oncocross Ltd., Seoul, Republic of Korea.
  • Gwang Yeul Yun
    Center for Research and Development, Oncocross Ltd., Seoul, Republic of Korea.
  • Yi Rang Kim
    Center for Research and Development, Oncocross Ltd., Seoul, Republic of Korea.
  • Jin Woo Choi
    Interdisciplinary Program in Bioengineering, Graduate School, Seoul National University, Seoul, Korea.