Title:Network Medicine and High Throughput Screening
VOLUME: 10 ISSUE: 3
Author(s):Robert E. Smith, Kevin Tran and Ralph H. Vocque
Affiliation:Total Diet and Pesticide Research Center, U.S. Food and Drug Administration, 11510 W 80th St, Lenexa, KS 66214, USA.
Keywords:Allo-network drugs, autopoiesis, high content screening, high throughput screening, network medicine.
Abstract:A new paradigm is emerging in modern drug discovery. It is a fusion of traditional and modern medicine, phenotypic
and targeted drug discovery, or systems and reductionist thinking. This is exemplified by using a combination of
network medicine and high throughput screening. It blends the use of physiologically relevant biological systems with the
high throughput and statistical robustness of modern assay technologies. The basic principles of network theory and tools
of network medicine are described. Scale-free networks and their organizing principles are discussed. They are emergent
properties of living, autopoietic systems. This includes networks of people who do high throughput screening (HTS), and
microscopic networks of ions, metabolites, DNA, RNA, proteins, lipids, carbohydrates, viruses, bacteria, fungi, human
cells and tissues. Databases have been constructed based on the metabolome, genome, transcriptome, proteome, lipidome,
glycocode, virome, bacteriome and many others. Modern HTS can be used to examine the interactions of many parts of
the complex human network. High content screening (HCS) can look at perturbations that occur when test compounds are
added to single cells. Allo-network drugs can have effects far beyond a single protein and can be transmitted to other
cells. Interactions and hidden connections can be revealed, with the goal of developing new drugs that have few, if any
harmful side effects and are effective against multi-drug resistant cancer cells or bacteria.
