Using a systems-based approach to overcome reductionist strategies in the development of diagnostics

Abstract

Systems biology is a recent addition to the necessary but insufficient reductionist approach used in biological research. Systems biology is focused on understanding living things as a function of their various interactions at multiple levels: not simply as a sum of all their individual parts at any one level. This integrative approach yields predictive models of the normal state, the disease state and therapeutic actions. Although molecular biology has collected an enormous amount of information, including the sequencing of the entire human genome in the year 2000, few real-world applications have resulted from this molecular approach. The pharmaceutical industry's R&D expenditure has increased substantially since 2000, but the number of approved therapeutics has dropped simultaneously, due in part to over-reliance on reductionist genomic, and not systems, approaches. Instead of using reductionist genomics approaches alone, genomics should be incorporated into a multi-level systems biology approach to develop diagnostics and therapeutics.

Keywords::

• epigenetics
• genomic variability
• molecular biology
• multifactorial
• reductionism
• systems biology
• systems diagnostic
• transposons

Financial & competing interests disclosure

The author is part-owner of BioRegenerative Sciences, Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Genomics has been over relied on in the last decade.

• • Molecular biology has made major strides, but is insufficient for the development of diagnostics.

• • The genome is mutable.

• • DNA is not the only transmitter of inheritance.

• • The genome from cell to cell in an individual is slightly different; there is no one genome for an individual.

• • Epigenetics is critical to understanding gene expression.

• • Many factors are important to diagnostic development including epigenetics of the individual, environment, age, diet, and epigenetics of both parents.

• • Multi-levels of analysis are important to developing diagnostics, including genetic, epigenetic, proteomic, metabolomic, imaging analysis, physiological, and other means.

• • New technologies and methodologies will lead to more powerful diagnostics, including the use of cellular and stem cell-based diagnostics and treatments, and new computational methodologies.

• • The Oslerian means of classifying disease will move to a systems classification of disease.