Guest Editorial: Special Issue on the Foundations of Systems Biology in Engineering (FOSBE)

The complete sequencing of the human genome has undoubtedly advanced the study of biology and the practice of medicine, including some dramatic and rapid advances in human health. This progress has been slowed, however, by the challenge of understanding how the genetic players, and their regulation, interact to yield systemic responses to disease and treatment. Taking a puzzle as an analogy for life, the landmark achievement of identifying the human genome provided a list of the possible puzzle pieces, but it did not provide the completed picture on the cover. The search since has focused on the relationships between this genomic information and the (individual or patient) systemic response or function—the “omics” efforts in mapping proteins (proteomics) and metabolites (metabolomics). The primary avenues in this search are: 1) defining the causal connections between the plethora of transcriptional, protein, and metabolite players; 2) linking these microscale networks to system-level response; and 3) capturing the dynamics of the system in response to changes at lower scales. The fields of systems biology, and its translational science counterpart systems medicine, have emerged as the bridge between reductionist molecular and cellular biology approaches and the systems-level understanding required to use this knowledge to advance the human condition.