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Bayesian inference of multi-point macromolecular architecture mixtures at nanometre resolution
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Embacher, Peter A., Germanova, Tsvetelina E., Roscioli, Emanuele, McAinsh, Andrew D. and Burroughs, Nigel J. (2022) Bayesian inference of multi-point macromolecular architecture mixtures at nanometre resolution. PLoS Computational Biology, 18 (12). e1010765. doi:10.1371/journal.pcbi.1010765 ISSN 1553-7358.
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WRAP-Bayesian-inference-of-multi-point-macromolecular-architecture-mixtures-at-nanometre-resolution-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (4Mb) | Preview |
Official URL: http://dx.doi.org/10.1371/journal.pcbi.1010765
Abstract
Gaussian spot fitting methods have significantly extended the spatial range where fluorescent microscopy can be used, with recent techniques approaching nanometre (nm) resolutions. However, small inter-fluorophore distances are systematically over-estimated for typical molecular scales. This bias can be corrected computationally, but current algorithms are limited to correcting distances between pairs of fluorophores. Here we present a flexible Bayesian computational approach that infers the distances and angles between multiple fluorophores and has several advantages over these previous methods. Specifically it improves confidence intervals for small lengths, estimates measurement errors of each fluorophore individually and infers the correlations between polygon lengths. The latter is essential for determining the full multi-fluorophore 3D architecture. We further developed the algorithm to infer the mixture composition of a heterogeneous population of multiple polygon states. We use our algorithm to analyse the 3D architecture of the human kinetochore, a macro-molecular complex that is essential for high fidelity chromosome segregation during cell division. Using triple fluorophore image data we unravel the mixture of kinetochore states during human mitosis, inferring the conformation of microtubule attached and unattached kinetochores and their proportions across mitosis. We demonstrate that the attachment conformation correlates with intersister tension and sister alignment to the metaphase plate.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Science > Mathematics Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Fluorescent polymers, Fluorescent polymers -- Mathematical models, Fluorescence microscopy , Proteins -- Structure -- Mathematical models | |||||||||||||||
| Journal or Publication Title: | PLoS Computational Biology | |||||||||||||||
| Publisher: | Public Library of Science | |||||||||||||||
| ISSN: | 1553-7358 | |||||||||||||||
| Official Date: | 27 December 2022 | |||||||||||||||
| Dates: |
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| Volume: | 18 | |||||||||||||||
| Number: | 12 | |||||||||||||||
| Article Number: | e1010765 | |||||||||||||||
| DOI: | 10.1371/journal.pcbi.1010765 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
| Date of first compliant deposit: | 23 January 2023 | |||||||||||||||
| Date of first compliant Open Access: | 25 January 2023 | |||||||||||||||
| RIOXX Funder/Project Grant: |
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