Biomarker Selection for Adaptive Systems.

Abstract

Biomarkers enable objective monitoring of a given cell or state in a biological system and are widely used in research, biomanufacturing, and clinical practice. However, identifying appropriate biomarkers that are both robustly measurable and capture a state accurately remains challenging. We present a framework for biomarker identification based upon observability guided sensor selection. Our methods, Dynamic Sensor Selection (DSS) and Structure-Guided Sensor Selection (SGSS), utilize temporal models and experimental data, offering a template for applying observability theory to data from biological systems. Unlike conventional methods that assume well-known, fixed dynamics, DSS adaptively select biomarkers or sensors that maximize observability while accounting for the time-varying nature of biological systems. Additionally, SGSS incorporates structural information and diverse data to identify sensors which are resilient against inaccuracies in our model of the underlying system. We validate our approaches by performing estimation on high dimensional systems derived from temporal gene expression data from partial observations. Our algorithms reliably identify known biomarkers and uncover new ones within our datasets. Additionally, integrating chromosome conformation and gene expression data addresses noise and uncertainty, enhancing the reliability of our biomarker selection approach for the genome.