In Silico Machine Learning Methods in Drug Development

2014 ◽  
Vol 14 (16) ◽  
pp. 1913-1922 ◽  
Author(s):  
Dimitar Dobchev ◽  
Girinath Pillai ◽  
Mati Karelson
2020 ◽  
Vol 39 (8) ◽  
pp. 1900178
Author(s):  
Jiajing Hu ◽  
Yingchun Cai ◽  
Weihua Li ◽  
Guixia Liu ◽  
Yun Tang

Author(s):  
Xiaoxiao Zhang ◽  
Piaopiao Zhao ◽  
Zhiyuan Wang ◽  
Xuan Xu ◽  
Guixia Liu ◽  
...  

2016 ◽  
Vol 5 (2) ◽  
pp. 570-582 ◽  
Author(s):  
Chen Zhang ◽  
Yuan Zhou ◽  
Shikai Gu ◽  
Zengrui Wu ◽  
Wenjie Wu ◽  
...  

A series of models of hERG blockage were built using five machine learning methods based on 13 molecular descriptors, five types of fingerprints and molecular descriptors combining fingerprints at four blockage thresholds.


RSC Advances ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. 6697-6703 ◽  
Author(s):  
Qin Wang ◽  
Xiao Li ◽  
Hongbin Yang ◽  
Yingchun Cai ◽  
Yinyin Wang ◽  
...  

Chemical fingerprints combined with machine learning methods were used to build binary classification models for predicting the potential EC/EI of compounds.


2021 ◽  
Vol 12 ◽  
Author(s):  
Pau Romero ◽  
Miguel Lozano ◽  
Francisco Martínez-Gil ◽  
Dolors Serra ◽  
Rafael Sebastián ◽  
...  

The combination of machine learning methods together with computational modeling and simulation of the cardiovascular system brings the possibility of obtaining very valuable information about new therapies or clinical devices through in-silico experiments. However, the application of machine learning methods demands access to large cohorts of patients. As an alternative to medical data acquisition and processing, which often requires some degree of manual intervention, the generation of virtual cohorts made of synthetic patients can be automated. However, the generation of a synthetic sample can still be computationally demanding to guarantee that it is clinically meaningful and that it reflects enough inter-patient variability. This paper addresses the problem of generating virtual patient cohorts of thoracic aorta geometries that can be used for in-silico trials. In particular, we focus on the problem of generating a cohort of patients that meet a particular clinical criterion, regardless the access to a reference sample of that phenotype. We formalize the problem of clinically-driven sampling and assess several sampling strategies with two goals, sampling efficiency, i.e., that the generated individuals actually belong to the target population, and that the statistical properties of the cohort can be controlled. Our results show that generative adversarial networks can produce reliable, clinically-driven cohorts of thoracic aortas with good efficiency. Moreover, non-linear predictors can serve as an efficient alternative to the sometimes expensive evaluation of anatomical or functional parameters of the organ of interest.


2020 ◽  
Vol 21 (4) ◽  
pp. 1523 ◽  
Author(s):  
Madhu Sudhana Saddala ◽  
Anton Lennikov ◽  
Hu Huang

Glucose-6-Phosphate Dehydrogenase (G6PD) is a ubiquitous cytoplasmic enzyme converting glucose-6-phosphate into 6-phosphogluconate in the pentose phosphate pathway (PPP). The G6PD deficiency renders the inability to regenerate glutathione due to lack of Nicotine Adenosine Dinucleotide Phosphate (NADPH) and produces stress conditions that can cause oxidative injury to photoreceptors, retinal cells, and blood barrier function. In this study, we constructed pharmacophore-based models based on the complex of G6PD with compound AG1 (G6PD activator) followed by virtual screening. Fifty-three hit molecules were mapped with core pharmacophore features. We performed molecular descriptor calculation, clustering, and principal component analysis (PCA) to pharmacophore hit molecules and further applied statistical machine learning methods. Optimal performance of pharmacophore modeling and machine learning approaches classified the 53 hits as drug-like (18) and nondrug-like (35) compounds. The drug-like compounds further evaluated our established cheminformatics pipeline (molecular docking and in silico ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis). Finally, five lead molecules with different scaffolds were selected by binding energies and in silico ADMET properties. This study proposes that the combination of machine learning methods with traditional structure-based virtual screening can effectively strengthen the ability to find potential G6PD activators used for G6PD deficiency diseases. Moreover, these compounds can be considered as safe agents for further validation studies at the cell level, animal model, and even clinic setting.


2019 ◽  
Vol 8 (3) ◽  
pp. 341-352 ◽  
Author(s):  
Lin Liu ◽  
Hongbin Yang ◽  
Yingchun Cai ◽  
Qianqian Cao ◽  
Lixia Sun ◽  
...  

Six machine learning methods combined with descriptors or fingerprints were employed to predict chemical toxicity on marine crustaceans.


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