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Weighted voting-based consensus clustering for chemical structure databases

Saeed F, Ahmed A, Shamsir MS, Salim N

J Comput Aided Mol Des, 2014 Jun;28(6):675-84.
PMID: 24830925 DOI: 10.1007/s10822-014-9750-2

The cluster-based compound selection is used in the lead identification process of drug discovery and design. Many clustering methods have been used for chemical databases, but there is no clustering method that can obtain the best results under all circumstances. However, little attention has been focused on the use of combination methods for chemical structure clustering, which is known as consensus clustering. Recently, consensus clustering has been used in many areas including bioinformatics, machine learning and information theory. This process can improve the robustness, stability, consistency and novelty of clustering. For chemical databases, different consensus clustering methods have been used including the co-association matrix-based, graph-based, hypergraph-based and voting-based methods. In this paper, a weighted cumulative voting-based aggregation algorithm (W-CVAA) was developed. The MDL Drug Data Report (MDDR) benchmark chemical dataset was used in the experiments and represented by the AlogP and ECPF_4 descriptors. The results from the clustering methods were evaluated by the ability of the clustering to separate biologically active molecules in each cluster from inactive ones using different criteria, and the effectiveness of the consensus clustering was compared to that of Ward's method, which is the current standard clustering method in chemoinformatics. This study indicated that weighted voting-based consensus clustering can overcome the limitations of the existing voting-based methods and improve the effectiveness of combining multiple clusterings of chemical structures.

Matched MeSH terms: Databases, Pharmaceutical*
Consensus methods for combining multiple clusterings of chemical structures

Saeed F, Salim N, Abdo A

J Chem Inf Model, 2013 May 24;53(5):1026-34.
PMID: 23581471 DOI: 10.1021/ci300442u

The goal of consensus clustering methods is to find a consensus partition that optimally summarizes an ensemble and improves the quality of clustering compared with single clustering algorithms. In this paper, an enhanced voting-based consensus method was introduced and compared with other consensus clustering methods, including co-association-based, graph-based, and voting-based consensus methods. The MDDR and MUV data sets were used for the experiments and were represented by three 2D fingerprints: ALOGP, ECFP_4, and ECFC_4. The results were evaluated based on the ability of the clustering method to separate active from inactive molecules in each cluster using four criteria: F-measure, Quality Partition Index (QPI), Rand Index (RI), and Fowlkes-Mallows Index (FMI). The experiments suggest that the consensus methods can deliver significant improvements for the effectiveness of chemical structures clustering.

Matched MeSH terms: Databases, Pharmaceutical
Sequence Symmetry Analysis as a Signal Detection Tool for Potential Heart Failure Adverse Events in an Administrative Claims Database

Wahab IA, Pratt NL, Ellett LK, Roughead EE

Drug Saf, 2016 Apr;39(4):347-54.
PMID: 26798053 DOI: 10.1007/s40264-015-0391-8

The potential for routine sequence symmetry analysis (SSA) signal detection in health claims databases to detect new safety signals of medicines is unknown.

Matched MeSH terms: Databases, Pharmaceutical*
Applications of Ensemble Docking in Potential Inhibitor Screening for Mycobacterium tuberculosis Isocitrate Lyase Using a Local Plant Database

Lee YV, Choi SB, Wahab HA, Lim TS, Choong YS

J Chem Inf Model, 2019 05 28;59(5):2487-2495.
PMID: 30840452 DOI: 10.1021/acs.jcim.8b00963

Isocitrate lyase (ICL) is a persistent factor for the survival of dormant stage Mycobacterium tuberculosis (MTB), thus a potential drug target for tuberculosis treatment. In this work, ensemble docking approach was used to screen for potential inhibitors of ICL. The ensemble conformations of ICL active site were obtained from molecular dynamics simulation on three dimer form systems, namely the apo ICL, ICL in complex with metabolites (glyoxylate and succinate), and ICL in complex with substrate (isocitrate). Together with the ensemble conformations and the X-ray crystal structures, 22 structures were used for the screening against Malaysian Natural Compound Database (NADI). The top 10 compounds for each ensemble conformation were selected. The number of compounds was then further narrowed down to 22 compounds that were within the Lipinski's Rule of Five for drug-likeliness and were also docked into more than one ensemble conformation. Theses 22 compounds were furthered evaluate using whole cell assay. Some compounds were not commercially available; therefore, plant crude extracts were used for the whole cell assay. Compared to itaconate (the known inhibitor of ICL), crude extracts from Manilkara zapota, Morinda citrifolia, Vitex negundo, and Momordica charantia showed some inhibition activity. The MIC/MBC value were 12.5/25, 12.5/25, 0.78/1.6, and 0.39/1.6 mg/mL, respectively. This work could serve as a preliminary study in order to narrow the scope for high throughput screening in the future.

Matched MeSH terms: Databases, Pharmaceutical*
Comparison of psychotropic prescriptions between oncology and cardiology inpatients: result from a pharmacy database in a teaching hospital in Malaysia

Ng CG, Mohamed S, Wern TY, Haris A, Zainal NZ, Sulaiman AH

Asian Pac J Cancer Prev, 2014;15(10):4261-4.
PMID: 24935381

OBJECTIVE: To examine the prescription rates in cancer patients of three common psychotropic drugs: anxiolytic/ hypnotic, antidepressant and antipsychotic.
MATERIALS AND METHODS: In this retrospective cohort study, data were extracted from the pharmacy database of University Malaya Medical Center (UMMC) responsible for dispensing records of patients stored in the pharmacy's Medication Management and Use System (Ascribe). We analyzed the use of psychotropics in patients from the oncology ward and cardiology from 2008 to 2012. Odds ratios (ORs) were adjusted for age, gender and ethnicity.
RESULTS: A total of 3,345 oncology patients and 8,980 cardiology patients were included. Oncology patients were significantly more often prescribed psychotropic drugs (adjusted OR: anxiolytic/hypnotic=5.55 (CI: 4.64-6.63); antidepressants=6.08 (CI: 4.83-7.64) and antipsychotics=5.41 (CI: 4.17-7.02). Non-Malay female cancer patients were at significantly higher risk of anxiolytic/hypnotic use.
CONCLUSIONS: Psychotropic drugs prescription is common in cancer patients. Anxiolytic/hypnotic prescription rates are significantly higher in non-Malay female patients in Malaysia.

Matched MeSH terms: Databases, Pharmaceutical/statistics & numerical data
Fulltext Drug ReposER: a web server for predicting similar amino acid arrangements to known drug binding interfaces for potential drug repositioning

Ab Ghani NS, Ramlan EI, Firdaus-Raih M

Nucleic Acids Res, 2019 07 02;47(W1):W350-W356.
PMID: 31106379 DOI: 10.1093/nar/gkz391

A common drug repositioning strategy is the re-application of an existing drug to address alternative targets. A crucial aspect to enable such repurposing is that the drug's binding site on the original target is similar to that on the alternative target. Based on the assumption that proteins with similar binding sites may bind to similar drugs, the 3D substructure similarity data can be used to identify similar sites in other proteins that are not known targets. The Drug ReposER (DRug REPOSitioning Exploration Resource) web server is designed to identify potential targets for drug repurposing based on sub-structural similarity to the binding interfaces of known drug binding sites. The application has pre-computed amino acid arrangements from protein structures in the Protein Data Bank that are similar to the 3D arrangements of known drug binding sites thus allowing users to explore them as alternative targets. Users can annotate new structures for sites that are similarly arranged to the residues found in known drug binding interfaces. The search results are presented as mappings of matched sidechain superpositions. The results of the searches can be visualized using an integrated NGL viewer. The Drug ReposER server has no access restrictions and is available at http://mfrlab.org/drugreposer/.

Matched MeSH terms: Databases, Pharmaceutical