Drug discovery suffers from high attrition because compounds initially deemed as promising can later show ineffectiveness or toxicity resulting from a poor understanding of their activity profile. In this work, we describe a deep self-normalizing neural network model for the prediction of molecular pathway association and evaluate its performance, showing an AUC ranging from 0.69 to 0.91 on a set of compounds extracted from ChEMBL and from 0.81 to 0.83 on an external data set provided by Novartis. We finally discuss the applicability of the proposed model in the domain of lead discovery. A usable application is available via PlayMolecule.org .
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jcim.8b00711 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Towards the photodeposition of SiGe-type materials oligomers of cyclogermapentenes and cyclosilapentenes.
Dalton Trans
January 2025
Department of Chemistry, University of Alberta, 11227 Saskatchewan Dr, Edmonton, Alberta, T6G 2G2, Canada.
This article provides an alternative pathway towards cyclosilapentenes (, SiH2-iPr and SpiroSi) involving the use of Rieke magnesium to activate the requisite dienes for synthesis. Subsequent metal-mediated dehydrocoupling of cyclosilapentene and mixtures with another cyclogermapentene gives oligomers with backbone Si-Si (number average molecular weight, = 1.0 kDa) and Si-Ge ( = 1.
View Article and Find Full Text PDFResistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance.
J Virol
January 2025
SA MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, South Africa.
The Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity.
View Article and Find Full Text PDFVaccinia growth factor-dependent modulation of the mTORC1-CAD axis upon nutrient restriction.
J Virol
January 2025
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
The molecular mechanisms by which vaccinia virus (VACV), the prototypical member of the poxviridae family, reprograms host cell metabolism remain largely unexplored. Additionally, cells sense and respond to fluctuating nutrient availability, thereby modulating metabolic pathways to ensure cellular homeostasis. Understanding how VACV modulates metabolic pathways in response to nutrient signals is crucial for understanding viral replication mechanisms, with the potential for developing antiviral therapies.
View Article and Find Full Text PDFGlutathione reductase plays a role in the metabolism of methylmercury degradation in .
Microbiol Spectr
January 2025
School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, China.
Unlabelled: Mercury pollution is a kind of heavy metal pollution with great harm and strong toxicity which exists worldwide. Some microorganisms can convert highly toxic methylmercury into inorganic mercury compounds with significantly reduced toxicity. This is an effective means of methylmercury pollution remediation.
View Article and Find Full Text PDFMultiplexed Molecular Endophenotypes Help Identify Hub Genes in Non-Small Cell Lung Cancer: Unlocking Next-Generation Cancer Phenomics.
OMICS
January 2025
Department of Biotechnology, Brainware University, Barasat, West Bengal, India.
Next-generation cancer phenomics by deployment of multiple molecular endophenotypes coupled with high-throughput analyses of gene expression offer veritable opportunities for triangulation of discovery findings in non-small cell lung cancer (NSCLC) research. This study reports differentially expressed genes in NSCLC using publicly available datasets (GSE18842 and GSE229253), uncovering 130 common genes that may potentially represent crucial molecular signatures of NSCLC. Additionally, network analyses by GeneMANIA and STRING revealed significant coexpression and interaction patterns among these genes, with four notable hub genes-, , and -identified as pivotal in NSCLC progression.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!