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Learning dynamical information from static protein and sequencing data
Many complex processes, from protein folding to neuronal network dynamics, can be described as stochastic exploration of a high-dimensional energy landscape. Although efficient algorithms for cluster detection in high-dimensional spaces have been developed over the last two decades, considerably les...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879630/ https://www.ncbi.nlm.nih.gov/pubmed/31772168 http://dx.doi.org/10.1038/s41467-019-13307-x |
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author | Pearce, Philip Woodhouse, Francis G. Forrow, Aden Kelly, Ashley Kusumaatmaja, Halim Dunkel, Jörn |
author_facet | Pearce, Philip Woodhouse, Francis G. Forrow, Aden Kelly, Ashley Kusumaatmaja, Halim Dunkel, Jörn |
author_sort | Pearce, Philip |
collection | PubMed |
description | Many complex processes, from protein folding to neuronal network dynamics, can be described as stochastic exploration of a high-dimensional energy landscape. Although efficient algorithms for cluster detection in high-dimensional spaces have been developed over the last two decades, considerably less is known about the reliable inference of state transition dynamics in such settings. Here we introduce a flexible and robust numerical framework to infer Markovian transition networks directly from time-independent data sampled from stationary equilibrium distributions. We demonstrate the practical potential of the inference scheme by reconstructing the network dynamics for several protein-folding transitions, gene-regulatory network motifs, and HIV evolution pathways. The predicted network topologies and relative transition time scales agree well with direct estimates from time-dependent molecular dynamics data, stochastic simulations, and phylogenetic trees, respectively. Owing to its generic structure, the framework introduced here will be applicable to high-throughput RNA and protein-sequencing datasets, and future cryo-electron microscopy (cryo-EM) data. |
format | Online Article Text |
id | pubmed-6879630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68796302019-11-29 Learning dynamical information from static protein and sequencing data Pearce, Philip Woodhouse, Francis G. Forrow, Aden Kelly, Ashley Kusumaatmaja, Halim Dunkel, Jörn Nat Commun Article Many complex processes, from protein folding to neuronal network dynamics, can be described as stochastic exploration of a high-dimensional energy landscape. Although efficient algorithms for cluster detection in high-dimensional spaces have been developed over the last two decades, considerably less is known about the reliable inference of state transition dynamics in such settings. Here we introduce a flexible and robust numerical framework to infer Markovian transition networks directly from time-independent data sampled from stationary equilibrium distributions. We demonstrate the practical potential of the inference scheme by reconstructing the network dynamics for several protein-folding transitions, gene-regulatory network motifs, and HIV evolution pathways. The predicted network topologies and relative transition time scales agree well with direct estimates from time-dependent molecular dynamics data, stochastic simulations, and phylogenetic trees, respectively. Owing to its generic structure, the framework introduced here will be applicable to high-throughput RNA and protein-sequencing datasets, and future cryo-electron microscopy (cryo-EM) data. Nature Publishing Group UK 2019-11-26 /pmc/articles/PMC6879630/ /pubmed/31772168 http://dx.doi.org/10.1038/s41467-019-13307-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Pearce, Philip Woodhouse, Francis G. Forrow, Aden Kelly, Ashley Kusumaatmaja, Halim Dunkel, Jörn Learning dynamical information from static protein and sequencing data |
title | Learning dynamical information from static protein and sequencing data |
title_full | Learning dynamical information from static protein and sequencing data |
title_fullStr | Learning dynamical information from static protein and sequencing data |
title_full_unstemmed | Learning dynamical information from static protein and sequencing data |
title_short | Learning dynamical information from static protein and sequencing data |
title_sort | learning dynamical information from static protein and sequencing data |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879630/ https://www.ncbi.nlm.nih.gov/pubmed/31772168 http://dx.doi.org/10.1038/s41467-019-13307-x |
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