A biological function based biomarker panel optimization process
Abstract
Implementation of multi-gene biomarker panels identified from high throughput data, including microarray or next generation sequencing, need to be adapted to a platform suitable in a clinical setting such as quantitative polymerase chain reaction. However, technical challenges when transitioning from one measurement platform to another, such as inconsistent measurement results can affect panel development. We describe a process to overcome the challenges by replacing poor performing genes during platform transition and reducing the number of features without impacting classification performance. This approach assumes that a diagnostic panel reflects the effect of dysregulated biological processes associated with a disease, and genes involved in the same biological processes and coordinately affected by a disease share a similar discriminatory power. The utility of this optimization process was assessed using a published sepsis diagnostic panel. Substitution of more than half of the genes and/or reducing genes based on biological processes did not negatively affect the performance of the sepsis diagnostic panel. Our results suggest a systematic gene substitution and reduction process based on biological function can be used to alleviate the challenges associated with clinical development of biomarker panels.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 14, 2019
- Source ID
- 10.1038/s41598-019-43779-2
Entities
People
- Kai Wang
- Kathie-Anne Walters
- Min Young Lee
- Taek-kyun Kim
Organizations
- Defense Threat Reduction Agency
- National Institutes of Health
- United States Department of Defense