LncTx: A network-based method to repurpose drugs acting on the survival-related lncRNAs in lung cancer
Journal
Computational and Structural Biotechnology Journal
Journal Volume
19
Pages
3990-4002
Date Issued
2021-01-01
Author(s)
Abstract
Despite the fact that an increased amount of survival-related lncRNAs have been found in cancer, few drugs that target lncRNAs are approved for treatment. Here, we developed a network-based algorithm, LncTx, to repurpose the medications that potentially act on survival-related lncRNAs in lung cancer. We used eight survival-related lncRNAs derived from our previous study to test the efficacy of this method. LncTx calculates the shortest path length (proximity) between the drug targets and the lncRNA-correlated proteins in the protein–protein interaction network (interactome). LncTx contains seven different proximity measures, which are calculated in the unweighted or weighted interactome. First, to test the performance of LncTx in predicting correct indication of drugs, we benchmarked the proximity measures based on the accuracy of differentiating anticancer drugs from non-anticancer drugs. The closest proximity weighted by clustering coefficient (closestCC) has the best performance (AUC around 0.8) compared to other proximity measures across all survival-related lncRNAs. The majority of the other six proximity measures have decent performance as well, with AUC greater than 0.7. Second, to evaluate whether LncTx can repurpose the drugs effectively acting on the lncRNAs, we clustered the drugs according to their proximities by hierarchical clustering. The drugs with smaller proximity (proximal drugs) were proved to be more effective than the drugs with larger proximity (distal drugs). In conclusion, LncTx enables us to accurately identify anticancer drugs and can potentially be an index to repurpose effective agents acting on survival-related lncRNAs in lung cancer.
Subjects
Drug repurposing | Long non-coding RNA-based therapy | Network proximity
SDGs
Other Subjects
Diseases; Proteins; Anticancer drug; Drug repurposing; Interactome; Long non-coding RNA-based therapy; Lung Cancer; Network proximity; Network-based; Network-based algorithm; Performance; Proximity measure; Biological organs; antineoplastic agent; long noncoding RNA ENSG00000230163; long noncoding RNA ENSG00000232611; long noncoding RNA ENSG00000258365; long noncoding RNA ENSG00000268650; long noncoding RNA ENSG00000271646; long noncoding RNA ENSG00000271828; long noncoding RNA ENSG00000272402; long noncoding RNA ENSG00000273226; long untranslated RNA; saracatinib; topotecan; unclassified drug; voxtalisib; area under the curve; Article; cancer survival; comparative effectiveness; controlled study; drug efficacy; drug indication; drug repositioning; drug sensitivity; genetic algorithm; hierarchical clustering; human; IC50; interactomics; lung cancer; protein protein interaction
Publisher
Elsevier B.V.
Type
journal article