A deep learning-based approach to model anomalous diffusion of membrane proteins: the case of the nicotinic acetylcholine receptor

Abstract: We present a concatenated deep-learning multiple neural network system for the analysis of single-molecule trajectories. We apply this machine learning-based analysis to characterize the translational diffusion of the nicotinic acetylcholine receptor at the plasma membrane, experimentally...

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Autores principales: Buena Maizon, Héctor, Barrantes, Francisco José
Formato: Artículo
Lenguaje:Inglés
Publicado: Oxford University Press 2022
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Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/14114
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id I33-R139-123456789-14114
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic INTELIGENCIA ARTIFICIAL
APRENDIZAJE AUTOMÁTICO
APRENDIZAJE PROFUNDO
PROTEÍNA DE MEMBRANA
RECEPTOR DE NEUROTRANSMISORES
RECEPTOR DE ACETILCOLINA
COLESTEROL
SEGUIMIENTO DE PARTÍCULAS INDIVIDUALES
MICROSCOPÍA DE SUPERRESOLUCIÓN
spellingShingle INTELIGENCIA ARTIFICIAL
APRENDIZAJE AUTOMÁTICO
APRENDIZAJE PROFUNDO
PROTEÍNA DE MEMBRANA
RECEPTOR DE NEUROTRANSMISORES
RECEPTOR DE ACETILCOLINA
COLESTEROL
SEGUIMIENTO DE PARTÍCULAS INDIVIDUALES
MICROSCOPÍA DE SUPERRESOLUCIÓN
Buena Maizon, Héctor
Barrantes, Francisco José
A deep learning-based approach to model anomalous diffusion of membrane proteins: the case of the nicotinic acetylcholine receptor
topic_facet INTELIGENCIA ARTIFICIAL
APRENDIZAJE AUTOMÁTICO
APRENDIZAJE PROFUNDO
PROTEÍNA DE MEMBRANA
RECEPTOR DE NEUROTRANSMISORES
RECEPTOR DE ACETILCOLINA
COLESTEROL
SEGUIMIENTO DE PARTÍCULAS INDIVIDUALES
MICROSCOPÍA DE SUPERRESOLUCIÓN
description Abstract: We present a concatenated deep-learning multiple neural network system for the analysis of single-molecule trajectories. We apply this machine learning-based analysis to characterize the translational diffusion of the nicotinic acetylcholine receptor at the plasma membrane, experimentally interrogated using superresolution optical microscopy. The receptor protein displays a heterogeneous diffusion behavior that goes beyond the ensemble level, with individual trajectories exhibiting more than one diffusive state, requiring the optimization of the neural networks through a hyperparameter analysis for different numbers of steps and durations, especially for short trajectories (<50 steps) where the accuracy of the models is most sensitive to localization errors. We next use the statistical models to test for Brownian, continuous-time random walk and fractional Brownian motion, and introduce and implement an additional, two-state model combining Brownian walks and obstructed diffusion mechanisms, enabling us to partition the two-state trajectories into segments, each of which is independently subjected to multiple analysis. The concatenated multi-network system evaluates and selects those physical models that most accurately describe the receptor’s translational diffusion. We show that the two-state Brownian-obstructed diffusion model can account for the experimentally observed anomalous diffusion (mostly subdiffusive) of the population and the heterogeneous single-molecule behavior, accurately describing the majority (72.5 to 88.7% for α-bungarotoxin-labeled receptor and between 73.5 and 90.3% for antibody-labeled molecules) of the experimentally observed trajectories, with only ~15% of the trajectories fitting to the fractional Brownian motion model.
format Artículo
author Buena Maizon, Héctor
Barrantes, Francisco José
author_facet Buena Maizon, Héctor
Barrantes, Francisco José
author_sort Buena Maizon, Héctor
title A deep learning-based approach to model anomalous diffusion of membrane proteins: the case of the nicotinic acetylcholine receptor
title_short A deep learning-based approach to model anomalous diffusion of membrane proteins: the case of the nicotinic acetylcholine receptor
title_full A deep learning-based approach to model anomalous diffusion of membrane proteins: the case of the nicotinic acetylcholine receptor
title_fullStr A deep learning-based approach to model anomalous diffusion of membrane proteins: the case of the nicotinic acetylcholine receptor
title_full_unstemmed A deep learning-based approach to model anomalous diffusion of membrane proteins: the case of the nicotinic acetylcholine receptor
title_sort deep learning-based approach to model anomalous diffusion of membrane proteins: the case of the nicotinic acetylcholine receptor
publisher Oxford University Press
publishDate 2022
url https://repositorio.uca.edu.ar/handle/123456789/14114
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