Extremal events dictate population growth rate inference

Fuente: arXiv
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Main Authors: GrandPre, Trevor, Levien, Ethan, Amir, Ariel
Format: Preprint
Published: 2025
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author GrandPre, Trevor
Levien, Ethan
Amir, Ariel
author_facet GrandPre, Trevor
Levien, Ethan
Amir, Ariel
contents Recent methods have been developed to map single-cell lineage statistics to population growth. Because population growth selects for exponentially rare phenotypes, these methods inherently depend on sampling large deviations from finite data, which introduces systematic errors. A comprehensive understanding of these errors in the context of finite data remains elusive. To address this gap, we study the error in growth rate estimates across different models. We show that under the usual bias-variance decomposition, the bias can be decomposed into a finite-time bias and nonlinear averaging bias. We demonstrate that finite-time bias, which dominates at short times, can be mitigated by fitting its monotonic behavior. In contrast, at longer times, nonlinear averaging bias becomes the predominant source of error, leading to a phase transition. This transition can be understood through the Random Energy Model, a mean-field model of disordered systems, where a few lineages dominate the estimator. Applying these methods to experimental data demonstrates that correcting for biases in lineage-based approaches yields consistent results for the long-term growth rate across multiple methods and enables the reverse-engineering of dynamic models. This new framework provides a quantitative understanding of growth rate estimators, clarifies the conditions under which they can be effectively applied to finite data, and introduces model-free approaches for studying the connections between physiology and cell growth.
format Preprint
id arxiv_https___arxiv_org_abs_2501_08404
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Extremal events dictate population growth rate inference
GrandPre, Trevor
Levien, Ethan
Amir, Ariel
Statistical Mechanics
Biological Physics
Populations and Evolution
Other Statistics
Recent methods have been developed to map single-cell lineage statistics to population growth. Because population growth selects for exponentially rare phenotypes, these methods inherently depend on sampling large deviations from finite data, which introduces systematic errors. A comprehensive understanding of these errors in the context of finite data remains elusive. To address this gap, we study the error in growth rate estimates across different models. We show that under the usual bias-variance decomposition, the bias can be decomposed into a finite-time bias and nonlinear averaging bias. We demonstrate that finite-time bias, which dominates at short times, can be mitigated by fitting its monotonic behavior. In contrast, at longer times, nonlinear averaging bias becomes the predominant source of error, leading to a phase transition. This transition can be understood through the Random Energy Model, a mean-field model of disordered systems, where a few lineages dominate the estimator. Applying these methods to experimental data demonstrates that correcting for biases in lineage-based approaches yields consistent results for the long-term growth rate across multiple methods and enables the reverse-engineering of dynamic models. This new framework provides a quantitative understanding of growth rate estimators, clarifies the conditions under which they can be effectively applied to finite data, and introduces model-free approaches for studying the connections between physiology and cell growth.
title Extremal events dictate population growth rate inference
topic Statistical Mechanics
Biological Physics
Populations and Evolution
Other Statistics
url https://arxiv.org/abs/2501.08404