A point of inflection and reflection on systems chemical biology
For the past several decades, chemical biologists have been leveraging chemical principles for understanding biology, tackling disease, and biomanufacturing, while systems biologists have holistically applied computation and genome-scale experimental tools to the same problems. About a decade ago, the benefit of combining the philosophies of chemical biology with systems biology into systems chemical biology was advocated, with the potential to systematically understand the way small molecules affect biological systems. Recently, there has been an explosion in new technologies that permit massive expansion in the scale of biological experimentation, increase access to more diverse chemical space, and enable powerful computational interpretation of large datasets. Fueled by these rapidly increasing capabilities, systems chemical biology is now at an inflection point, poised to enter a new era of more holistic and integrated scientific discovery. Systems chemical biology is primed to reveal an integrated understanding of fundamental biology and to discover new chemical probes to comprehensively dissect and systematically understand that biology, thereby providing a path to novel strategies for discovering therapeutics, designing drug combinations, avoiding toxicity, and harnessing beneficial polypharmacology. In this Review, we examine the emergence of new capabilities driving us to this inflection point in systems chemical biology, and highlight holistic approaches and opportunities that are arising from integrating chemical biology with a systems-level understanding of the intersection of biology and chemistry.