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BACKGROUND In silico analyses are increasingly being used to support mode-of-action investigations; however many such approaches do not utilise the large amounts of inactive data held in chemogenomic repositories. The objective of this work is concerned with the integration of such bioactivity data in the target prediction of orphan compounds to produce the(More)
Integrating gene expression profiles with certain proteins can improve our understanding of the fundamental mechanisms in protein-ligand binding. This paper spotlights the integration of gene expression data and target prediction scores, providing insight into mechanism of action (MoA). Compounds are clustered based upon the similarity of their predicted(More)
Diversity selection is a frequently applied strategy for assembling high-throughput screening libraries, making the assumption that a diverse compound set increases chances of finding bioactive molecules. Based on previous work on experimental 'affinity fingerprints', in this study, a novel diversity selection method is benchmarked that utilizes predicted(More)
BACKGROUND An in silico mechanism-of-action analysis protocol was developed, comprising molecule bioactivity profiling, annotation of predicted targets with pathways and calculation of enrichment factors to highlight targets and pathways more likely to be implicated in the studied phenotype. RESULTS The method was applied to a cytotoxicity phenotypic(More)
The increase of publicly available bioactivity data has led to the extensive development and usage of in silico bioactivity prediction algorithms. A particularly popular approach for such analyses is the multiclass Naïve Bayes, whose output is commonly processed by applying empirically-derived likelihood score thresholds. In this work, we describe a(More)
The simultaneous increase of computational power and the availability of chemical and biological data have contributed to the recent popularity of in silico bioactivity prediction algorithms. Such methods are commonly used to infer the 'Mechanism of Action' of small molecules and they can also be employed in cases where full bioactivity profiles have not(More)
Understanding the mode of action of small molecules is critical for drug research, both with respect to efficacy and anticipated side effects. Given that many compounds act on multiple targets simultaneously, it appears that linking single targets to outcomes is no longer sufficient. Hence, in this work we explore machine learning methods for rationalising(More)
Traditional Chinese medicine (TCM) still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs) of 45 TCM therapeutic action (sub)classes from in silico target prediction algorithms, whose target was later annotated with Kyoto(More)
Nanomaterials are increasingly used in healthcare and consumer products. The European community seeks solutions to assess the safety of these materials with experimental research data. Ideally, read across and predictive toxicology approaches can then be used to answer questions if a class of metal oxides is genotoxic or not. If successful, this will(More)
G protein-coupled receptors (GPCRs) are a major family of membrane receptors in eukaryotic cells and play a crucial role in various biological processes. They represent a family of protein targets with significant therapeutic value, and accordingly more than 30% of prescription drugs are GPCR ligands [1]. Extending previous attempts to map the(More)