Portfolio item: Coursework research (for INFO-I571, Chemical Info Tech/Cheminformatics, SP13)

Validation of Semantic Link Association Prediction (SLAP) by using quantitative luminance map visualizations of predicted binding strengths of antidepressants on putative CNS targets

Date Submitted: 30 April 2013

(Note: This web page contains only the abstract for the paper. If you want to read the entire paper as submitted, please view the full project paper as a PDF.) [1.1MB]

Abstract

Antidepressants (ADs) are a very diverse class of chemical compounds used in the treatment of Major Depressive Disorder (MDD), an affliction of the central nervous system (CNS). Furthermore, ADs represent a significant share of the pharmaceutical market, and are thus suited to analysis. SLAP (Semantic Link Association Prediction), a web application project by Chen et al, is designed to match chemicals to various gene/protein binding targets with a probability (p) value. SLAP predicts binding affinities semantically when no explicit binding study is found in its database. In this study, a luminance map visualization of SLAP scores between antidepressants and the proteins they are thought to target is created. It was found that Tanimoto clustering was a poor choice of array order in terms of visualization, and that a more coherent luminance map was created by performing a second-pass, confounded analysis on the original chemical order array with respect to SLAP predictions on their targets. This second-pass luminance map yielded more parsimonious conclusions, including the visualization of a "noradrenergic" pattern in drugs known to be noradrenergic. The second-pass clustering and visualization also more properly clustered selegiline and rasagiline, two MAO (monoamine oxidase) inhibitors, which were shown to have unusual activities via SLAP, not interacting with receptors but as expected, with the MAO enzyme.

Abstract Reference: Chen, B. et al. (2012). Semantic Link Association Predictor (SLAP) (Web application). Bloomington, IN: Indiana University Bloomington. Retrieved from http://cheminfov.informatics.indiana.edu:8080/slap/.

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