title: Automatic detection of diffusion modes within biological membranes using back-propagation neural network.
abstract: BACKGROUND
  Single particle tracking (SPT) is nowadays one of the most popular technique to probe spatio-temporal dynamics of proteins diffusing within the plasma membrane. Indeed membrane components of eukaryotic cells are very dynamic molecules and can diffuse according to different motion modes. Trajectories are often reconstructed frame-by-frame and dynamic properties often evaluated using mean square displacement (MSD) analysis. However, to get statistically significant results in tracking experiments, analysis of a large number of trajectories is required and new methods facilitating this analysis are still needed.
  
  
  RESULTS
  In this study we developed a new algorithm based on back-propagation neural network (BPNN) and MSD analysis using a sliding window. The neural network was trained and cross validated with short synthetic trajectories. For simulated and experimental data, the algorithm was shown to accurately discriminate between Brownian, confined and directed diffusion modes within one trajectory, the 3 main of diffusion encountered for proteins diffusing within biological membranes. It does not require a minimum number of observed particle displacements within the trajectory to infer the presence of multiple motion states. The size of the sliding window was small enough to measure local behavior and to detect switches between different diffusion modes for segments as short as 20 frames. It also provides quantitative information from each segment of these trajectories. Besides its ability to detect switches between 3 modes of diffusion, this algorithm is able to analyze simultaneously hundreds of trajectories with a short computational time.
  
  
  CONCLUSIONS
  This new algorithm, implemented in powerful and handy software, provides a new conceptual and versatile tool, to accurately analyze the dynamic behavior of membrane components.
authors.affiliation: Inserm, U1054, Montpellier, France.|Université de Montpellier, CNRS, UMR 5048, Centre de Biochimie Structurale, Montpellier, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Dosset
authors.affiliation: Inserm, U1054, Montpellier, France.|Université de Montpellier, CNRS, UMR 5048, Centre de Biochimie Structurale, Montpellier, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Rassam
authors.affiliation: Inserm, U1054, Montpellier, France.|Université de Montpellier, CNRS, UMR 5048, Centre de Biochimie Structurale, Montpellier, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Fernandez
authors.affiliation: Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, New York, NY, USA.
authors.forename: Cedric
authors.initials: C
authors.lastname: Espenel
authors.affiliation: Inserm, U1004, Villejuif, France.|Institut André Lwoff, Université Paris 11, Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Rubinstein
authors.affiliation: Inserm, U1054, Montpellier, France.|Université de Montpellier, CNRS, UMR 5048, Centre de Biochimie Structurale, Montpellier, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Margeat
authors.affiliation: Inserm, U1054, Montpellier, France. pem@cbs.cnrs.fr.|Université de Montpellier, CNRS, UMR 5048, Centre de Biochimie Structurale, Montpellier, France. pem@cbs.cnrs.fr.|Centre de Biochimie Structurale, 29, rue de Navacelles, 34090, Montpellier, France. pem@cbs.cnrs.fr.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Milhiet
mesh_terms: D000465:Algorithms; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D004058:Diffusion; D008954:Models, Biological; D009038:Motion; D016571:Neural Networks, Computer
keywords: Diffusion; Membrane; Neural network; Single molecule tracking; Trajectory