Annotated chemical libraries

Savchuk NP, Balakin KV, Tkachenko SE. Exploring the chemogenomic knowledge space with annotated chemical libraries. Curr Opin Chem Biol 2004 8 412-17. 

Under this framework. Fig. 6 shows the basic pieces for constructing annotated chemical libraries. On the one hand, proteins should be stored using the appropriate annotation under their respective protein-family classification schemes (in this case, nuclear receptors). On the other hand, molecules should be stored using a unique hierarchical identifier. The link between the two entities (molecules and proteins) would be defined by pharmacological data (activity). The use of a certain criteria would then allow to construct a binary annotation matrix, from which the mapping of the chemogenomic space is established. 

The adoption of hierarchical classification schemes for both chemical and biological entities makes the storage and analysis of annotated chemical libraries computationally tractable and reduced to managing binary annotation matrices. These binary matrices are often visually illustrated as heatmaps (Fig. 7), where red indicates that the molecule is annotated to a target (i.e. shows biological activity under a certain criteria), while green... 

In this chapter, we describe a protocol for the systematic perturbation of patient-derived cell lines using small-molecule probes, which is both scalable to high-throughput workflow and generalizable to a variety of assays. In the protocol presented here, multiple patient-derived lymphoblastoid cell lines either mutant or wild type at a defined genetic locus (e.g., HNF4a) are perturbed by an annotated chemical library. After sufficient incubation, cells are subjected to a phenotypic assay, in this case a luminescence-based readout of cellular ATP content, that aims to quantify the effect of compounds on oxidative phosphorylation, viability, or other relevant traits. The effect of each compound is expressed as a metric that reflects the difference in compound-induced phenotypes between mutant and wild-type cells. These ratios are then... 

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