Precise measurements of chromatin diffusion dynamics by modeling using Gaussian processes

Guilherme M. Oliveira (), Attila Oravecz, Dominique Kobi, Manon Maroquenne, Kerstin Bystricky, Tom Sexton () and Nacho Molina ()
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Guilherme M. Oliveira: University of Strasbourg
Attila Oravecz: University of Strasbourg
Dominique Kobi: University of Strasbourg
Manon Maroquenne: University of Strasbourg
Kerstin Bystricky: Centre de Biologie Integrative (CBI) UPS, CNRS
Tom Sexton: University of Strasbourg
Nacho Molina: University of Strasbourg

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract The spatiotemporal organization of chromatin influences many nuclear processes: from chromosome segregation to transcriptional regulation. To get a deeper understanding of these processes, it is essential to go beyond static viewpoints of chromosome structures, to accurately characterize chromatin’s diffusion properties. We present GP-FBM: a computational framework based on Gaussian processes and fractional Brownian motion to extract diffusion properties from stochastic trajectories of labeled chromatin loci. GP-FBM uses higher-order temporal correlations present in the data, therefore, outperforming existing methods. Furthermore, GP-FBM allows to interpolate incomplete trajectories and account for substrate movement when two or more particles are present. Using our method, we show that average chromatin diffusion properties are surprisingly similar in interphase and mitosis in mouse embryonic stem cells. We observe surprising heterogeneity in local chromatin dynamics, correlating with potential regulatory activity. We also present GP-Tool, a user-friendly graphical interface to facilitate usage of GP-FBM by the research community.

Date: 2021
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DOI: 10.1038/s41467-021-26466-7

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