Similar Datasets
Project description:Target protein-based drug and research compound discovery has been undeniably successful strategy in life science research, yet many diseases and biological processes lack obvious targets to enable these approaches. Here, to overcome this major challenge we have developed a deep-learning based efficacy prediction system (DLEPS) to identify potent agents to treat diverse diseases; DLEPS was trained using L1000 project chemical induced “changes of transcriptional profiles” (CTP) data as input. Strikingly, we found that the CTPs for previously unexamined molecules were precisely predicted (0.74 Pearson correlation coefficient). We used DLEPS to examine 4 disorders, and experimentally validated that perillen, chikusetsusaponin IV, trametinib, and liquiritin confer disease-relevant impacts against obesity, hyperuricemia, NASH, and COVID-19, respectively. Importantly, DLEPS also uncovered the biological insight that the MEK-ERK signaling pathway should be understood as a target for developing anti-NASH agents. Beyond illustrating that DLEPS is an effective tool for drug repurposing and development with diverse diseases (including those lacking targets), our study shows how diverse transcriptomics datasets can be harnessed to identify inhibitors and activator chemicals that can expand the scope of biological investigations well beyond mutant-bases analyses.
2023-03-31 | GSE165174 | GEO
Project description:Target protein-based drug and research compound discovery has been undeniably successful strategy in life science research, yet many diseases and biological processes lack obvious targets to enable these approaches. Here, to overcome this major challenge we have developed a deep-learning based efficacy prediction system (DLEPS) to identify potent agents to treat diverse diseases; DLEPS was trained using L1000 project chemical induced “changes of transcriptional profiles” (CTP) data as input. Strikingly, we found that the CTPs for previously unexamined molecules were precisely predicted (0.74 Pearson correlation coefficient). We used DLEPS to examine 4 disorders, and experimentally validated that perillen, chikusetsusaponin IV, trametinib, and liquiritin confer disease-relevant impacts against obesity, hyperuricemia, NASH, and COVID-19, respectively. Importantly, DLEPS also uncovered the biological insight that the MEK-ERK signaling pathway should be understood as a target for developing anti-NASH agents. Beyond illustrating that DLEPS is an effective tool for drug repurposing and development with diverse diseases (including those lacking targets), our study shows how diverse transcriptomics datasets can be harnessed to identify inhibitors and activator chemicals that can expand the scope of biological investigations well beyond mutant-bases analyses.
2023-03-31 | GSE165173 | GEO
Project description:Target protein-based drug and research compound discovery has been undeniably successful strategy in life science research, yet many diseases and biological processes lack obvious targets to enable these approaches. Here, to overcome this major challenge we have developed a deep-learning based efficacy prediction system (DLEPS) to identify potent agents to treat diverse diseases; DLEPS was trained using L1000 project chemical induced “changes of transcriptional profiles” (CTP) data as input. Strikingly, we found that the CTPs for previously unexamined molecules were precisely predicted (0.74 Pearson correlation coefficient). We used DLEPS to examine 4 disorders, and experimentally validated that perillen, chikusetsusaponin IV, trametinib, and liquiritin confer disease-relevant impacts against obesity, hyperuricemia, NASH, and COVID-19, respectively. Importantly, DLEPS also uncovered the biological insight that the MEK-ERK signaling pathway should be understood as a target for developing anti-NASH agents. Beyond illustrating that DLEPS is an effective tool for drug repurposing and development with diverse diseases (including those lacking targets), our study shows how diverse transcriptomics datasets can be harnessed to identify inhibitors and activator chemicals that can expand the scope of biological investigations well beyond mutant-bases analyses.
2023-03-31 | GSE165171 | GEO
Project description:A Deep Learning based Efficacy Prediction System for Drug Discovery
| PRJNA693487 | ENA
Project description:A Deep Learning based Efficacy Prediction System for Drug Discovery [Perillen]
| PRJNA693496 | ENA
Project description:A Deep Learning based Efficacy Prediction System for Drug Discovery [Trametinib]
| PRJNA693497 | ENA
Project description:A Deep Learning based Efficacy Prediction System for Drug Discovery [Chikusetsusaponin IV]
| PRJNA693494 | ENA
Project description:Blockade of the human ether-à-go-go-related gene (hERG) channel by small molecules induces the prolongation of the QT interval which leads to fatal cardiotoxicity and accounts for the withdrawal or severe restrictions on the use of many approved drugs. In this study, we develop a deep learning approach, termed deephERG, for prediction of hERG blockers of small molecules in drug discovery and postmarketing surveillance. In total, we assemble 7,889 compounds with well-defined experimental data on the hERG and with diverse chemical structures. We find that deephERG models built by a multitask deep neural network (DNN) algorithm outperform those built by single-task DNN, naı̈ve Bayes (NB), support vector machine (SVM), random forest (RF), and graph convolutional neural network (GCNN). Specifically, the area under the receiver operating characteristic curve (AUC) value for the best model of deephERG is 0.967 on the validation set. Furthermore, based on 1,824 U.S. Food and Drug Administration (FDA) approved drugs, 29.6% drugs are computationally identified to have potential hERG inhibitory activities by deephERG, highlighting the importance of hERG risk assessment in early drug discovery. Finally, we showcase several novel predicted hERG blockers on approved antineoplastic agents, which are validated by clinical case reports, experimental evidence, and the literature. In summary, this study presents a powerful deep learning-based tool for risk assessment of hERG-mediated cardiotoxicities in drug discovery and postmarketing surveillance.
| S-EPMC6489130 | biostudies-literature
Project description: Not available
| S-EPMC10872075 | biostudies-literature
Project description:Drug discovery is a rigorous process that requires billion dollars of investments and decades of research to bring a molecule "from bench to a bedside". While virtual docking can significantly accelerate the process of drug discovery, it ultimately lags the current rate of expansion of chemical databases that already exceed billions of molecular records. This recent surge of small molecules availability presents great drug discovery opportunities, but also demands much faster screening protocols. In order to address this challenge, we herein introduce Deep Docking (DD), a novel deep learning platform that is suitable for docking billions of molecular structures in a rapid, yet accurate fashion. The DD approach utilizes quantitative structure-activity relationship (QSAR) deep models trained on docking scores of subsets of a chemical library to approximate the docking outcome for yet unprocessed entries and, therefore, to remove unfavorable molecules in an iterative manner. The use of DD methodology in conjunction with the FRED docking program allowed rapid and accurate calculation of docking scores for 1.36 billion molecules from the ZINC15 library against 12 prominent target proteins and demonstrated up to 100-fold data reduction and 6000-fold enrichment of high scoring molecules (without notable loss of favorably docked entities). The DD protocol can readily be used in conjunction with any docking program and was made publicly available.
| S-EPMC7318080 | biostudies-literature