MetaGTM: VISUALIZATION AND ANALYSIS OF THE CHEMICAL LIBRARY SPACE

Abstract

In chemical library analysis, it may be useful to describe libraries as individual items, rather than as collections of compounds. This is particularly true for ultra-large non-cherry pickable compound mixtures, such as DNA-Encoded Libraries (DELs). In this sense, the Chemical Library Space (CLS) is useful for the management of a portfolio of libraries, just like Chemical Space (CS) helps managing a portfolio of molecules. Several possible CLSs were previously defined using vectorial library representations obtained from Generative Topographic Mapping (GTM). Given the steadily growing number of DEL designs, the CLS becomes “crowded”, and requires analysis tools beyond pairwise library comparison. Therefore, herein we investigate the cartography of CLS on meta-(µ)GTMs – “meta” to remind that these are maps of the CLS, itself based on responsibility vectors issued by regular CS GTMs. 2,5K DELs and ChEMBL (reference) were projected on the µGTM, producing landscapes of library-specific properties. These describe both inter-library similarity and intrinsic library characteristics in the same view, herewith facilitating the selection of the best project-specific libraries.