Knowledge from Small-Molecule Screening and Profiling Data.

We are pleased to work with the Journal of Biomolecular Screening (JBS) to present a special issue on generating Knowledge from Small-Molecule Screening and Profiling Data. Since its inception as an avenue for probe-and drug-discovery activities, high-throughput screening (HTS) has produced large data sets with great potential to enrich our understanding of the interactions of chemical matter with biological systems. In most cases, such activities focus on discovering a " needle in a haystack " to perturb a particular cellular process (probe) or find a starting point (lead) from which a treatment (drug) might be developed for a disease. High-throughput diversity screening is a well-established activity in pharmaceutical and agrochemical research, with a body of evidence to support its effectiveness. 1 Indeed, HTS can no longer be considered a novel or disruptive technology , given it has been practiced for around 20 years! That does not mean, however, that there is nothing to improve. In the realm of data analysis, this special issue illustrates how much there is still to do, and how much still to learn, particularly as screening technology allows us to study multiparametric cellular responses. With the advent of chemical biology repositories like ChemBank, 2 PubChem, 3 and ChEMBL, 4 it rapidly became clear that small-molecule screening data sets on common compound collections could be more than the sum of their parts, especially when aggregated and publicly shared. The US National Institutes of Health (NIH) Roadmap formally recognized this reality 10 years ago by establishing the Molecular Libraries Program (initially the Molecular Libraries Screening Network [MLSCN] and subsequently the Molecular Libraries Probe Production Centers Network [MLPCN]). Increasingly, as data from this network's activities have become available via PubChem, 3 and later the BioAssay Research Database (BARD), 5 it has become possible to imagine cross-sectional analyses that make use of data from multiple experiments simultaneously, even those performed by separate investigators worldwide. This special issue on Knowledge from Small-Molecule Screening and Profiling Data opens with a review article 5 that presents perspective on the development of BARD, a fourth-generation repository and knowledge environment for small-molecule science. At its core, BARD aims to present the successful experiment in public probe discovery undertaken by the NIH Roadmap and to contextualize screening and follow-up data from multiple diverse Network Centers collected over multiple years. BARD also aims to pave the way for future work in chemical biology research using structured vocabularies …