Dataset Information

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

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.

SUBMITTER: Kim SK

PROVIDER: S-EPMC7843016 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Kim Sun Kyung SK Goughnour Peter C PC Lee Eui Jin EJ Kim Myeong Hyun MH Chae Hee Jin HJ Yun Gwang Yeul GY Kim Yi Rang YR Choi Jin Woo JW

PloS one 20210128 1

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 bee ...[more]

PMID: 33507975

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Project description:Background: Lung adenocarcinoma is a common malignant tumor that ranks second in the world and has a high mortality rate. G protein-coupled receptors (GPCRs) have been reported to play an important role in cancer; however, G protein-coupled receptor-associated features have not been adequately investigated. Methods: In this study, GPCR-related genes were screened at single-cell and bulk transcriptome levels based on AUcell, single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network (WGCNA) analysis. And a new machine learning framework containing 10 machine learning algorithms and their multiple combinations was used to construct a consensus G protein-coupled receptor-related signature (GPCRRS). GPCRRS was validated in the training set and external validation set. We constructed GPCRRS-integrated nomogram clinical prognosis prediction tools. Multi-omics analyses included genomics, single-cell transcriptomics, and bulk transcriptomics to gain a more comprehensive understanding of prognostic features. We assessed the response of risk subgroups to immunotherapy and screened for personalized drugs targeting specific risk subgroups. Finally, the expression of key GPCRRS genes was verified by RT-qPCR. Results: In this study, we identified 10 GPCR-associated genes that were significantly associated with the prognosis of lung adenocarcinoma by single-cell transcriptome and bulk transcriptome. Univariate and multivariate showed that the survival rate was higher in low risk than in high risk, which also suggested that the model was an independent prognostic factor for LUAD. In addition, we observed significant differences in biological function, mutational landscape, and immune cell infiltration in the tumor microenvironment between high and low risk groups. Notably, immunotherapy was also relevant in the high and low risk groups. In addition, potential drugs targeting specific risk subgroups were identified. Conclusion: In this study, we constructed and validated a lung adenocarcinoma G protein-coupled receptor-related signature, which has an important role in predicting the prognosis of lung adenocarcinoma and the effect of immunotherapy. It is hypothesized that LDHA, GPX3 and DOCK4 are new potential targets for lung adenocarcinoma, which can achieve breakthroughs in prognosis prediction, targeted prevention and treatment of lung adenocarcinoma and provide important guidance for anti-tumor.

Dataset Information

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

Publications

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

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