Editorial [Hot Topic:Chemical Genomics (Guest Editor: Anuj Kumar)]

The availability of a fully sequenced genome is an enticing biological resource - sufficiently enticing, in fact, to spur the establishment of well over 300 eukaryotic genome-sequencing projects at this time. The investment of labor and resources in these projects is obviously sizable, and the expected scientific gain from these projects is equally sizable. In truth, the realistic advancement in biological knowledge resulting from a sequenced genome will likely never fulfill the associated promise; however, genomics has indeed affected a wide array of disciplines, with an increasing number of studies combining, in particular, chemistry and genomics. Over the last few years, researchers in academics and industry have undertaken many interesting projects interfacing large-scale genomic methods with synthetic chemical tools - an interface that is broadly termed “chemical genomics.” Chemical genomics occurs at the intersection of genomics, bioinformatics, proteomics, chemoinformatics, structural biology, analytical chemistry, combinatorial chemistry, and chemical biology. Thus, new discoveries in these individual fields are, in turn, driving the development of chemical genomics. Moreover, rapidly maturing ideas that merge traditionally disparate areas are providing additional research opportunities, and the development of new technology is further expanding research avenues. This emerging field has already been successful in identifying new drug targets, in providing powerful chemical probes and in illuminating the mechanism of action of new chemical entities. Future studies will build upon this scientific foundation. In this issue of Combinatorial Chemistry & High Throughput Screening, we present an overview of chemical genomics, authored by leaders in fields of research relevant to this discipline. Here, we summarize influential studies using chemical genomic screens and highlight recent technological developments with applicability to chemical genomics. This issue brings together researchers from both academics and industry, with unique and complementary insight into the current state of the art (and future potential) in marrying genomic resources and methodologies to combinatorial chemistry and small molecule screening. In particular, model organisms are gaining increasing popularity in drug-based screening studies; here, Nike Bharucha and I provide an overview of chemical genomic studies in yeast using genome-wide collections of mutants and other genomic approaches to help identify pathways and proteins targeted by small-molecule drugs. Recent studies have also utilized small molecule-based screens to provide insight into specific biological problems. In this issue, Fang et al. discuss applications of small molecules in studying various aspects of stem cell differentiation. Ratika Krishnamurthy and Dustin Maly review experimental techniques for the determination of protein kinase inhibitor selectivity and further summarize important insights gained from these studies. An exciting slate of technologies applicable on a genomic scale are now being developed and implemented as tools in small molecule screening and drug-based discovery; here, we review several recent technological advances with relevance to chemical genomics. Specifically, Jason Gestwicki and Paul Marinec present an overview of bifunctional molecules as tools in manipulating and probing protein-protein interactions, potentially on a genomic scale. Robert Powers offers a thorough review that summarizes applications of nuclear magnetic resonance energy (NMR) spectroscopy for the large-scale study of protein and protein-ligand complexes. Seergazhi Srivatsan and Michael Famulok review the development of functional nucleic acids, such as aptamers and ribozymes, and their utility in molecular screening. Tao and Chen in Heng Zhu’s group at Johns Hopkins provide a current overview of nascent protein microarray technologies with strong potential implications for future screens of small molecule-protein interactions. Finally, Bender et al. address the growing role of informatics in chemical genomics, both in predicting compound targets and in integrating and interpreting biological descriptors of drugs and small molecules....