New directions in incidence-dose modeling

• Published in: Trends in biotechnology (Regular ed.) Vol. 23; no. 3; pp. 122 - 127
• Main Authors: ANDERSEN, Melvin E, DENNISON, James E, THOMAS, Russell S, CONOLLY, Rory B
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Science 01.03.2005; Elsevier Limited
• Subjects: Biological and medical sciences; Biology; Biotechnology; Cell division; Chemicals; Circuits; Enzymes; Fundamental and applied biological sciences. Psychology; General aspects; Incidence; Kinases; Mathematical models; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Models, Biological; Ordinary differential equations; Population; Product development; Proteins; Risk assessment; Systems Biology - trends; Systems biology; Modeling
• ISSN: 0167-7799; 1879-3096
• DOI: 10.1016/j.tibtech.2005.01.007

Many cellular responses are quantal; that is, they either take place or they do not. Examples of "either-or" responses include cell replication, differentiation and apoptosis. Surprisingly, induction of suites of genes and coordinated phenotypic changes in cells are also often quantal, where embedded molecular circuitry creates on-off switches. Mechanistic incidence-dose (ID) models need to account for the quantal characteristics of cellular switches that contribute, in turn, to dose thresholds and to the incidence of biological responses in individuals. Interdisciplinary systems biology approaches create mechanistic ID models based on: (i) detailed knowledge of the cellular circuitry controlling signal transduction; (ii) evolving biological modeling tools describing cellular circuits and their perturbations by chemicals and (iii) high throughput, high coverage "omic" screens for examining cell signaling pathways and biological responses. These interdisciplinary approaches should produce novel, quantitative ID models for biological responses and greatly improve the biological basis of safety and risk assessments.