A systematic approach to prioritize drug targets using machine learning, a molecular descriptor-based classification model, and high-throughput screening of plant derived molecules: a case study in oral cancer

2015 ◽  
Vol 11 (12) ◽  
pp. 3362-3377 ◽  
Author(s):  
Vinay Randhawa ◽  
Anil Kumar Singh ◽  
Vishal Acharya
Keyword(s):  
Machine Learning ◽  
Oral Cancer ◽  
High Throughput ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Systematic Approach ◽  
Molecular Descriptor ◽  
Classification Model

Network-based and cheminformatics approaches identify novel lead molecules forCXCR4, a key gene prioritized in oral cancer.

scholarly journals A systematic approach to identify novel cancer drug targets using machine learning, inhibitor design and high-throughput screening

2014 ◽  
Vol 6 (7) ◽  
Author(s):  
Jouhyun Jeon ◽  
Satra Nim ◽  
Joan Teyra ◽  
Alessandro Datti ◽  
Jeffrey L Wrana ◽  
...  
Keyword(s):  
Machine Learning ◽  
High Throughput ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Systematic Approach ◽  
Cancer Drug ◽  
Inhibitor Design

scholarly journals Development of a Novel High-Throughput Screen and Identification of Small-Molecule Inhibitors of the Gα–RGS17 Protein–Protein Interaction Using AlphaScreen

2011 ◽  
Vol 16 (8) ◽  
pp. 869-877 ◽  
Author(s):  
Duncan I. Mackie ◽  
David L. Roman
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Protein Interaction ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Screening Method ◽  
Fold Increase ◽  
Rgs Proteins ◽  
High Throughput Screen ◽  
Protein Protein Interaction

In this study, the authors used AlphaScreen technology to develop a high-throughput screening method for interrogating small-molecule libraries for inhibitors of the Gαo–RGS17 interaction. RGS17 is implicated in the growth, proliferation, metastasis, and the migration of prostate and lung cancers. RGS17 is upregulated in lung and prostate tumors up to a 13-fold increase over patient-matched normal tissues. Studies show RGS17 knockdown inhibits colony formation and decreases tumorigenesis in nude mice. The screen in this study uses a measurement of the Gαo–RGS17 protein–protein interaction, with an excellent Z score exceeding 0.73, a signal-to-noise ratio >70, and a screening time of 1100 compounds per hour. The authors screened the NCI Diversity Set II and determined 35 initial hits, of which 16 were confirmed after screening against controls. The 16 compounds exhibited IC50 <10 µM in dose–response experiments. Four exhibited IC50 values <6 µM while inhibiting the Gαo–RGS17 interaction >50% when compared to a biotinylated glutathione-S-transferase control. This report describes the first high-throughput screen for RGS17 inhibitors, as well as a novel paradigm adaptable to many other RGS proteins, which are emerging as attractive drug targets for modulating G-protein-coupled receptor signaling.

scholarly journals Accelerating organic solar cell material's discovery: high-throughput screening and big data

2021 ◽  
Author(s):  
Xabier Rodríguez-Martínez ◽  
Enrique Pascual-San-José ◽  
Mariano Campoy-Quiles
Keyword(s):  
Machine Learning ◽  
Big Data ◽  
High Throughput ◽  
Organic Solar Cells ◽  
High Throughput Screening ◽  
Organic Solar Cell ◽  
State Of The Art ◽  
Review Article ◽  
Machine Learning Algorithms ◽  
Device Optimization

This review article presents the state-of-the-art in high-throughput computational and experimental screening routines with application in organic solar cells, including materials discovery, device optimization and machine-learning algorithms.

scholarly journals Action plan for hit identification (APHID): KAT6A as a case study

2020 ◽  
Vol 12 (5) ◽  
pp. 423-437 ◽  
Author(s):  
Xiangyan Yi ◽  
Lian Xue ◽  
Tim Thomas ◽  
Jonathan B Baell
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Action Plan ◽  
Hit Identification

Here, we describe our action plan for hit identification (APHID) that guides the process of hit triage, with elimination of less tractable hits and retention of more tractable hits. We exemplify the process with reference to our high-throughput screening (HTS) campaign against the enzyme, KAT6A, that resulted in successful identification of a tractable hit. We hope that APHID could serve as a useful, concise and digestible guide for those involved in HTS and hit triage, especially those that are relatively new to this exciting and continually evolving technology.

scholarly journals Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening

2019 ◽  
Vol 25 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Olivia W. Lee ◽  
Shelley Austin ◽  
Madison Gamma ◽  
Dorian M. Cheff ◽  
Tobie D. Lee ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
High Throughput ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Large Scale ◽  
Early Stage ◽  
Cancer Cell Line ◽  
Hek 293 ◽  
Cytotoxic Compounds

Cell-based phenotypic screening is a commonly used approach to discover biological pathways, novel drug targets, chemical probes, and high-quality hit-to-lead molecules. Many hits identified from high-throughput screening campaigns are ruled out through a series of follow-up potency, selectivity/specificity, and cytotoxicity assays. Prioritization of molecules with little or no cytotoxicity for downstream evaluation can influence the future direction of projects, so cytotoxicity profiling of screening libraries at an early stage is essential for increasing the likelihood of candidate success. In this study, we assessed the cell-based cytotoxicity of nearly 10,000 compounds in the National Institutes of Health, National Center for Advancing Translational Sciences annotated libraries and more than 100,000 compounds in a diversity library against four normal cell lines (HEK 293, NIH 3T3, CRL-7250, and HaCat) and one cancer cell line (KB 3-1, a HeLa subline). This large-scale library profiling was analyzed for overall screening outcomes, hit rates, pan-activity, and selectivity. For the annotated library, we also examined the primary targets and mechanistic pathways regularly associated with cell death. To our knowledge, this is the first study to use high-throughput screening to profile a large screening collection (>100,000 compounds) for cytotoxicity in both normal and cancer cell lines. The results generated here constitute a valuable resource for the scientific community and provide insight into the extent of cytotoxic compounds in screening libraries, allowing for the identification and avoidance of compounds with cytotoxicity during high-throughput screening campaigns.

scholarly journals A deep neural network model for packing density predictions and its application in the study of 1.5 million organic molecules

2019 ◽  
Vol 10 (36) ◽  
pp. 8374-8383 ◽  
Author(s):  
Mohammad Atif Faiz Afzal ◽  
Aditya Sonpal ◽  
Mojtaba Haghighatlari ◽  
Andrew J. Schultz ◽  
Johannes Hachmann
Keyword(s):  
Neural Network ◽  
Machine Learning ◽  
Refractive Index ◽  
High Throughput ◽  
Neural Network Model ◽  
High Throughput Screening ◽  
Deep Neural Network ◽  
Organic Molecules ◽  
High Refractive Index ◽  
Computational Pipeline

Computational pipeline for the accelerated discovery of organic materials with high refractive index via high-throughput screening and machine learning.

scholarly journals Platforms for High-Throughput Screening and Force Measurements on Fungi and Oomycetes

Micromachines ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 639
Author(s):  
Yiling Sun ◽  
Ayelen Tayagui ◽  
Sarah Sale ◽  
Debolina Sarkar ◽  
Volker Nock ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Control Strategies ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Plant Diseases ◽  
Force Measurements ◽  
Technical Developments ◽  
Alternative Drug

Pathogenic fungi and oomycetes give rise to a significant number of animal and plant diseases. While the spread of these pathogenic microorganisms is increasing globally, emerging resistance to antifungal drugs is making associated diseases more difficult to treat. High-throughput screening (HTS) and new developments in lab-on-a-chip (LOC) platforms promise to aid the discovery of urgently required new control strategies and anti-fungal/oomycete drugs. In this review, we summarize existing HTS and emergent LOC approaches in the context of infection strategies and invasive growth exhibited by these microorganisms. To aid this, we introduce key biological aspects and review existing HTS platforms based on both conventional and LOC techniques. We then provide an in-depth discussion of more specialized LOC platforms for force measurements on hyphae and to study electro- and chemotaxis in spores, approaches which have the potential to aid the discovery of alternative drug targets on future HTS platforms. Finally, we conclude with a brief discussion of the technical developments required to improve the uptake of these platforms into the general laboratory environment.

scholarly journals Uncertainty-Informed Deep Transfer Learning of PFAS Toxicity

2021 ◽  
Author(s):  
Jeremy Feinstein ◽  
ganesh sivaraman ◽  
Kurt Picel ◽  
Brian Peters ◽  
Alvaro Vazquez-Mayagoitia ◽  
...  
Keyword(s):  
Machine Learning ◽  
Transfer Learning ◽  
High Throughput ◽  
High Throughput Screening ◽  
Organic Chemical ◽  
Learning Method ◽  
Toxicity Data ◽  
Chemical Structures ◽  
Machine Learning Methods ◽  
Computational Methodology

In this article, we present our recent study on computational methodology for predicting the toxicity of PFAS known as “forever chemicals” based on chemical structures through evaluation of multiple machine learning methods. To address the scarcity of PFAS toxicity data, a deep “transfer learning” method has been investigated by leveraging toxicity information over the entire organic chemical domain and an uncertainty-informed workflow by incorporating SelectiveNet architecture, which can support future guidance of high throughput screening with knowledge of chemical structures, has been developed.

scholarly journals Application of Life Cycle Assessment and Machine Learning for High-Throughput Screening of Green Chemical Substitutes

2020 ◽  
Author(s):  
Xinzhe Zhu ◽  
Chi-Hung Ho ◽  
Xiaonan Wang
Keyword(s):  
Machine Learning ◽  
Life Cycle Assessment ◽  
Life Cycle ◽  
Production Process ◽  
Environmental Impacts ◽  
High Throughput ◽  
High Throughput Screening ◽  
Molecular Descriptors ◽  
Trifluoroacetic Anhydride ◽  
Chemical Materials

<p><a></a><a>The production process of many active pharmaceutical ingredients such as sitagliptin could cause severe environmental problems due to the use of toxic chemical materials and production infrastructure, energy consumption and wastes treatment. The environmental impacts of sitagliptin production process were estimated with life cycle assessment (LCA) method, which suggested that the use of chemical materials provided the major environmental impacts. Both methods of Eco-indicator 99 and ReCiPe endpoints confirmed that chemical feedstock accounted 83% and 70% of life-cycle impact, respectively. Among all the chemical materials used in the sitagliptin production process, </a><a>trifluoroacetic anhydride </a>was identified as the largest influential factor in most impact categories according to the results of ReCiPe midpoints method. Therefore, high-throughput screening was performed to seek for green chemical substitutes to replace the target chemical (i.e. trifluoroacetic anhydride) by the following three steps. Firstly, thirty most similar chemicals were obtained from two million candidate alternatives in PubChem database based on their molecular descriptors. Thereafter, deep learning neural network models were developed to predict life-cycle impact according to the chemicals in Ecoinvent v3.5 database with known LCA values and corresponding molecular descriptors. Finally, 1,2-ethanediyl ester was proved to be one of the potential greener substitutes after the LCA data of these similar chemicals were predicted using the well-trained machine learning models. The case study demonstrated the applicability of the novel framework to screen green chemical substitutes and optimize the pharmaceutical manufacturing process.</p>

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