Advanced Methods for Gene Network Identification and Noise Decomposition from Single-cell Data

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jun 8

PMID 38851792

Authors

Zhou Fang

Ankit Gupta

Sant Kumar

Mustafa Khammash

Affiliations

Soon will be listed here.

Abstract

Central to analyzing noisy gene expression systems is solving the Chemical Master Equation (CME), which characterizes the probability evolution of the reacting species' copy numbers. Solving CMEs for high-dimensional systems suffers from the curse of dimensionality. Here, we propose a computational method for improved scalability through a divide-and-conquer strategy that optimally decomposes the whole system into a leader system and several conditionally independent follower subsystems. The CME is solved by combining Monte Carlo estimation for the leader system with stochastic filtering procedures for the follower subsystems. We demonstrate this method with high-dimensional numerical examples and apply it to identify a yeast transcription system at the single-cell resolution, leveraging mRNA time-course experimental data. The identification results enable an accurate examination of the heterogeneity in rate parameters among isogenic cells. To validate this result, we develop a noise decomposition technique exploiting time-course data but requiring no supplementary components, e.g., dual-reporters.

Citing Articles

Advanced methods for gene network identification and noise decomposition from single-cell data.

Fang Z, Gupta A, Kumar S, Khammash M Nat Commun. 2024; 15(1):4911.

PMID: 38851792 PMC: 11162465. DOI: 10.1038/s41467-024-49177-1.

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