Dynamic sensor selection for biomarker discovery

J Joshua Pickard (Department of Computational Medicine & Bioinformatics) C Cooper Stansbury (Department of Computational Medicine & Bioinformatics) A Amit Surana (RTX Technology Research Center) L Lindsey Muir (Department of Computational Medicine & Bioinformatics) A Anthony Bloch (Department of Mathematics) I Indika Rajapakse (Department of Computational Medicine & Bioinformatics)

Abstract

Recent advances in biotechnologies enable monitoring of biological systems with unprecedented resolution, yet identifying and interpreting biological signals remains a major challenge in clinical and research settings. Classically, biomarkers are measurable indicators of the state of biological processes. Given the large number of molecules in modern datasets, a major challenge is identifying the best biomarkers for a particular setting. Here, we apply observability theory to establish a general methodology for biomarker selection. We demonstrate that observability identifies biologically meaningful sensors in a range of time series transcriptomics data. To address unique biological constraints, we introduce the method of dynamic sensor selection to maximize observability over time, thus enabling observability over regimes where system dynamics themselves are subject to change. Our observability-guided biomarker discovery framework extends to multiple data modalities, as demonstrated with the joint use of transcriptomics and chromosome conformation data. We demonstrate the generality of this approach by evaluating the observability of neural activity measured in movies and electroencephalograms. These applications highlight the broad utility of observability-guided biomarker selection, spanning agriculture, biomanufacturing, and neural systems.

Article Details

Volume / Issue Vol. 122, Issue 41
Published October 14, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (6)

J

Joshua Pickard

Department of Computational Medicine & Bioinformatics

C

Cooper Stansbury

Department of Computational Medicine & Bioinformatics

A

Amit Surana

RTX Technology Research Center

L

Lindsey Muir

Department of Computational Medicine & Bioinformatics

A

Anthony Bloch

Department of Mathematics

I

Indika Rajapakse

Department of Computational Medicine & Bioinformatics