LeadScope:  Software for Exploring Large Sets of Screening Data

Abstract

Modern approaches to drug discovery have dramatically increased the speed and quantity of compounds that are made and tested for potential potency. The task of collecting, organizing, and assimilating this information is a major bottleneck in the discovery of new drugs. We have developed LeadScope a novel, interactive computer program for visualizing, browsing, and interpreting chemical and biological screening data that can assist pharmaceutical scientists in finding promising drug candidates. The software organizes the chemical data by structural features familiar to medicinal chemists. Graphs are used to summarize the data, and structural classes are highlighted that are statistically correlated with biological activity.

Chemogenomics: an emerging strategy for rapid target and drug discovery

“…Statistical and chemoinformatics approaches for assessing the quality control of HTS data and for mining their chemical and biological information have been developed, for example, by incorporating pattern-detection methods for the identification of pipetting artefacts or for the detection of chemical-class-related effects. The development of chemoinformatics methods and procedures, such as RECURSIVE PARTITIONING, PHYLOGENETIC-LIKE TREE ALGORITHMS or BINARY QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSARS) [81][82][83][84][85][86][87] , which support the automatic identification of hits that are frequently identified by HTS, false positives and negatives, as well as structure-activity relationship (SAR) information, is essential for generating knowledge from HTS data 83,[88][89][90] . The myriad efforts that surround the design of appropriate analytic tools have to cope with the difficulty of integrating disparate types of information, especially PARSING and assimilating both chemical and genomics information data (tools such as Scitegic Pipeline pilot or Kensington Inforsense provide the required integration concepts (see online links box)).…”

3,5-Dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells

“…The Leadscope® software provides capabilities for looking at the relationships between families of structures that share a common structural feature and any biological response data (Roberts et al, 2000;Johnson et al, 2001;Blower et al, 2002;Cross et al, 2003;Yang et al, 2004). The software uses a dictionary of over 27,000 pre-defined structural features, such as common functional groups and heterocycles, which are used to classify the dataset (Roberts et al, 2000).…”

“…The software uses a dictionary of over 27,000 pre-defined structural features, such as common functional groups and heterocycles, which are used to classify the dataset (Roberts et al, 2000). In addition, new features were generated by combining different combination of features (Cross et al, 2003).…”

“…In addition, new features were generated by combining different combination of features (Cross et al, 2003). Statistics are calculated to determine whether there is a significant association between the chemical family and the biological response (Roberts et al, 2000). The software has been used and validated by many organizations, including the US FDA, to analyze the relationships between chemical structural features and toxicity data (Matthews et al, 2008).…”

Visualization and Grouping of Graph Patterns in Molecular Databases

“…Also our work is related to work done on the identification structure activity relationships (SARs) where one relates biological activity of molecules by analyzing their chemical structure [3,6] in the sense that in our work the structure of a graph is used to build a model. In [2,13,14] a statistical analysis was done on the presence of fragment substructures in active and inactive molecules. However our work is not concerned with the discovery of SARs, but with co-occurrence of subgraphs occurring in a collection of graphs.…”