A biological function based biomarker panel optimization process

Sci Rep. 2019 May 14;9(1):7365. doi: 10.1038/s41598-019-43779-2.


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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms*
  • Biomarkers / analysis*
  • Datasets as Topic
  • Gene Expression Profiling / methods*
  • High-Throughput Nucleotide Sequencing / methods
  • High-Throughput Screening Assays / methods*
  • Humans
  • Microarray Analysis / methods
  • Real-Time Polymerase Chain Reaction / methods
  • Sepsis / diagnosis
  • Sepsis / genetics
  • Signal Transduction / genetics


  • Biomarkers