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Lindsey Muir

Publications and source records attributed to Lindsey Muir.

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Dynamic Sensor Selection for Biomarker Discovery

Advances in methods of biological data collection are driving the rapid growth of comprehensive datasets across clinical and research settings. These datasets provide the opportunity to monitor biological systems in greater depth and at finer time steps than was achievable in the past. Classically, biomarkers are used to represent and track key aspects of a biological system. Biomarkers retain utility even with the availability of large datasets, since monitoring and interpreting changes in a vast number of molecules remains impractical. However, given the large number of molecules in these datasets, a major challenge is identifying the best biomarkers for a particular setting Here, we apply principles of observability theory to establish a general methodology for biomarker selection. We demonstrate that observability measures effectively identify biologically meaningful sensors in a range of time series transcriptomics data. Motivated by the practical considerations of biological systems, we introduce the method of dynamic sensor selection (DSS) to maximize observability over time, thus enabling observability over regimes where system dynamics themselves are subject to change. This observability framework is flexible, capable of modeling gene expression dynamics and using auxiliary data, including chromosome conformation, to select biomarkers. Additionally, we demonstrate the applicability of this approach beyond genomics by evaluating the observability of neural activity These applications demonstrate the utility of observability-guided biomarker selection for across a wide range of biological systems, from agriculture and biomanufacturing to neural applications and beyond.

q-bio.MN

An Algorithm for Cellular Reprogramming

The day we understand the time evolution of subcellular elements at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology, providing data-guided frameworks that allow us to develop better predictions about and methods for control over specific biological processes and system-wide cell behavior. In this paper we describe an approach to optimizing the use of transcription factors in the context of cellular reprogramming. We construct an approximate model for the natural evolution of a synchronized population of fibroblasts, based on data obtained by sampling the expression of some 22,083 genes at several times along the cell cycle. (These data are based on a colony of cells that have been cell cycle synchronized) In order to arrive at a model of moderate complexity, we cluster gene expression based on the division of the genome into topologically associating domains (TADs) and then model the dynamics of the expression levels of the TADs. Based on this dynamical model and known bioinformatics, we develop a methodology for identifying the transcription factors that are the most likely to be effective toward a specific cellular reprogramming task. The approach used is based on a device commonly used in optimal control. From this data-guided methodology, we identify a number of validated transcription factors used in reprogramming and/or natural differentiation. Our findings highlight the immense potential of dynamical models models, mathematics, and data guided methodologies for improving methods for control over biological processes.

q-bio.GN