The recent advancements in large-scale activity imaging of neuronal ensembles offer valuable opportunities to comprehend the process involved in generating brain activity patterns and understanding how information is transmitted between neurons or neuronal ensembles. However, existing methodologies for extracting the underlying properties that generate overall dynamics are still limited. In this study, we applied previously unexplored methodologies to analyze time-lapse 3D imaging (4D imaging) data of head neurons of the nematode Caenorhabditis elegans. By combining time-delay embedding with the independent component analysis, we successfully decomposed whole-brain activities into a small number of component dynamics. Through the integration of results from multiple samples, we extracted common dynamics from neuronal activities that exhibit apparent divergence across different animals. Notably, while several components show common cooperativity across samples, some component pairs exhibited distinct relationships between individual samples. We further developed time series prediction models of synaptic communications. By combining dimension reduction using the general framework, gradient kernel dimension reduction, and probabilistic modeling, the overall relationships of neural activities were incorporated. By this approach, the stochastic but coordinated dynamics were reproduced in the simulated whole-brain neural network. We found that noise in the nervous system is crucial for generating realistic whole-brain dynamics. Furthermore, by evaluating synaptic interaction properties in the models, strong interactions within the core neural circuit, variable sensory transmission and importance of gap junctions were inferred. Virtual optogenetics can be also performed using the model. These analyses provide a solid foundation for understanding information flow in real neural networks.

BACKGROUND: In the field of neuroscience, neural modules and circuits that control biological functions have been found throughout entire neural networks. Correlations in neural activity can be used to identify such neural modules. Recent technological advances enable us to measure whole-brain neural activity with single-cell resolution in several species including [Formula: see text]. Because current neural activity data in C. elegans contain many missing data points, it is necessary to merge results from as many animals as possible to obtain more reliable functional modules. RESULTS: In this work, we developed a new time-series clustering method, WormTensor, to identify functional modules using whole-brain activity data from C. elegans. WormTensor uses a distance measure, modified shape-based distance to account for the lags and the mutual inhibition of cell-cell interactions and applies the tensor decomposition algorithm multi-view clustering based on matrix integration using the higher orthogonal iteration of tensors (HOOI) algorithm (MC-MI-HOOI), which can estimate both the weight to account for the reliability of data from each animal and the clusters that are common across animals. CONCLUSION: We applied the method to 24 individual C. elegans and successfully found some known functional modules. Compared with a widely used consensus clustering method to aggregate multiple clustering results, WormTensor showed higher silhouette coefficients. Our simulation also showed that WormTensor is robust to contamination from noisy data. WormTensor is freely available as an R/CRAN package https://cran.r-project.org/web/packages/WormTensor .

Tracking many cells in time-lapse 3D image sequences is an important challenging task of bioimage informatics. Motivated by a study of brain-wide 4D imaging of neural activity in C. elegans, we present a new method of multi-cell tracking. Data types to which the method is applicable are characterized as follows: (i) cells are imaged as globular-like objects, (ii) it is difficult to distinguish cells on the basis of shape and size only, (iii) the number of imaged cells in the several-hundred range, (iv) movements of nearly-located cells are strongly correlated, and (v) cells do not divide. We developed a tracking software suite that we call SPF-CellTracker. Incorporating dependency on the cells' movements into the prediction model is the key for reducing the tracking errors: the cell switching and the coalescence of the tracked positions. We model the target cells' correlated movements as a Markov random field and we also derive a fast computation algorithm, which we call spatial particle filter. With the live-imaging data of the nuclei of C. elegans neurons in which approximately 120 nuclei of neurons were imaged, the proposed method demonstrated improved accuracy compared to the standard particle filter and the method developed by Tokunaga et al. (2014).

To measure the activity of neurons using whole-brain activity imaging, precise detection of each neuron or its nucleus is required. In the head region of the nematode C. elegans, the neuronal cell bodies are distributed densely in three-dimensional (3D) space. However, no existing computational methods of image analysis can separate them with sufficient accuracy. Here we propose a highly accurate segmentation method based on the curvatures of the iso-intensity surfaces. To obtain accurate positions of nuclei, we also developed a new procedure for least squares fitting with a Gaussian mixture model. Combining these methods enables accurate detection of densely distributed cell nuclei in a 3D space. The proposed method was implemented as a graphical user interface program that allows visualization and correction of the results of automatic detection. Additionally, the proposed method was applied to time-lapse 3D calcium imaging data, and most of the nuclei in the images were successfully tracked and measured.

MOTIVATION: Automated fluorescence microscopes produce massive amounts of images observing cells, often in four dimensions of space and time. This study addresses two tasks of time-lapse imaging analyses; detection and tracking of the many imaged cells, and it is especially intended for 4D live-cell imaging of neuronal nuclei of Caenorhabditis elegans. The cells of interest appear as slightly deformed ellipsoidal forms. They are densely distributed, and move rapidly in a series of 3D images. Thus, existing tracking methods often fail because more than one tracker will follow the same target or a tracker transits from one to other of different targets during rapid moves. RESULTS: The present method begins by performing the kernel density estimation in order to convert each 3D image into a smooth, continuous function. The cell bodies in the image are assumed to lie in the regions near the multiple local maxima of the density function. The tasks of detecting and tracking the cells are then addressed with two hill-climbing algorithms. The positions of the trackers are initialized by applying the cell-detection method to an image in the first frame. The tracking method keeps attacking them to near the local maxima in each subsequent image. To prevent the tracker from following multiple cells, we use a Markov random field (MRF) to model the spatial and temporal covariation of the cells and to maximize the image forces and the MRF-induced constraint on the trackers. The tracking procedure is demonstrated with dynamic 3D images that each contain >100 neurons of C.elegans. AVAILABILITY: http://daweb.ism.ac.jp/yoshidalab/crest/ismb2014 SUPPLEMENTARY INFORMATION: Supplementary data are available at http://daweb.ism.ac.jp/yoshidalab/crest/ismb2014

Network-based learning or e-Learning has been taking an important role in education as helpful education tools. However, it is difficult for teachers to retrieve education data from students or to obtain data from the student activities. Therefore, we have developed a problem solving environment (PSE) for the education and learning support: TSUNA-TASTE (Gallopoulos et al., 1991). The TSUNA-TASTE system collects the system-usage situation, the information for the windows used and the operation situation of the mouse and key board of all students. The data, which the system TSUNA-TASTE collects, are stored in a database on the TSUNA-TASTE system server. In this paper we present the structure of the TSUNA-TASTE system and detail structure of the network in the TSUNA-TASTE. The TSUNA-TASTE supports teachers and students in computer-based education. The TSUNA-TASTE may open a new helpful e-Learning world.

In computing sciences (e-Sciences) we need computer power, excellent algorithms and programming power in order to solve scientific problems leading to discoveries and development of innovative new products. So far, the computer power and the computing algorithms have been developed incredibly, and have provided enormous contributions to e-Sciences and e-Productions. Problem solving environments (PSE) support the programming power in e-Sciences and e-Productions, and have been studied actively for a few decades. In this paper a distributed PSE, named D-NCAS is presented, and a computer-assisted mathematical modeling support is also discussed in D-NCAS, which helps users solve partial differential equation (PDE) based problems in scientific computing. The D-NCAS PSE inputs a problem description and outputs a program flow, a C-language source code for the problem and also a document for the program. Each PSE module is distributed on networklinked distributed computers. The PSE holds all the information of the problem: PDEs, discretization scheme, mesh information, equation manipulation results, designed program structure, variable and constant definitions and program itself. The PSE concept has been opening a new direction for the computer-assisted programming or development of scientific simulation programs or CAEs.

A distributed problem solving environment (PSE) is proposed to help users solve partial differential equation (PDE) based problems in scientific computing. The system inputs a problem description and outputs a program flow, a C-language source code for the problem and also a document for the program. Each module is distributed on distributed computers. The PSE contains all the information of the problem, PDEs, discretization scheme, mesh information, equation manipulation results, designed program structure, variable and constant definitions and program itself. Therefore the documentation support module generates a document for the generated program and the problem itself in the PSE. The module liaison module generates an adapter module among the distributed PSE modules. The job execution service module deploys programs generated or prepared on distributed computer resources and helps users run the programs on the distributed computers. The concept of the distributed PSE extends the potential of conventional PSE systems