Web-Based Interfaces for Virtual C. elegans Neuron Model Definition, Network Configuration, Behavioral Experiment Definition and Experiment Results Visualization

Abstract

The Si elegans platform targets the complete virtualization of the nematode Caenorhabditis elegans, and its environment. This paper presents a suite of unified web-based Graphical User Interfaces (GUIs) as the main user interaction point, and discusses their underlying technologies and methods. The user-friendly features of this tool suite enable users to graphically create neuron and network models, and behavioral experiments, without requiring knowledge of domain-specific computer-science tools. The framework furthermore allows the graphical visualization of all simulation results using a worm locomotion and neural activity viewer. Models, experiment definitions and results can be exported in a machine-readable format, thereby facilitating reproducible and cross-platform execution of in silico C. elegans experiments in other simulation environments. This is made possible by a novel XML-based behavioral experiment definition encoding format, a NeuroML XML-based model generation and network configuration description language, and their associated GUIs. User survey data confirms the platform usability and functionality, and provides insights into future directions for web-based simulation GUIs of C. elegans and other living organisms. The tool suite is available online to the scientific community and its source code has been made available.

Keywords: C. elegans experiment definition and results visualization; NeuroML; behavioral experiment input encoding; biological neural networks; brain-inspired computation; in silico simulation; low entropy model specification (LEMS); neuronal activity visualization.

Figure 1

Overview of the proposed GUI toolsuite and underlying technologies within the global C. elegans simulation. The numbering reflects the typical workflow from graphical simulation definition to simulation execution and results visualization. GUI suite and underlying technologies block is detailed in the paper, while cross-platform emulation is summarized for the Si elegans specific implementation, providing references to papers with more detailed information.

Figure 2

Duration-based behavioral experiment stimuli classification examples. On the top of the graph, direct touch and plate tap mechanotaxis stimuli of the “interaction at specific time” type are represented twice, separated by a period without stimuli, for instance to test the worm's memory. Below, a permanent osmotic ring configuration (chemotaxis) of the “experiment-wide configuration” type is represented, which is defined from the experiment start until its end. Further below, a temperature change over time of the “interaction from t0 to t1” type for thermotaxis experiments is defined. Finally, two electric shock galvanotaxis stimuli of the “interaction from t0 to t1” type are represented to illustrate the possibility of presenting different types of duration-based stimuli simultaneously. An earlier version of this figure was originally presented in Epelde et al. (2015a).

Figure 3

Experiment definition section of an example behavioral experiment input encoding XML. At the top of the XML hierarchy (figure bottom), experimentDuration defines the experiment's duration in milliseconds. The three top-level duration-based classification elements are highlighted in green, i.e., interactionAtSpecificTime, interactionFromt0tot1 and experimentWideConf, corresponding to an interaction at a specific time t, an interaction from t0 to t1 and an experiment-wide stimulus configuration. The interactionFromt0tot1 element contains a galvanotaxis behavioral experiment type and the duration-related stimuli start and stop time definitions (i.e., eventStartTime and eventStopTime). The galvanotaxis behavioral experiment type contains a specific electric shock stimulus definition for the amplitude (in nA), duration (in ms) and frequency (in Hz) under the electricShockConf tag.

Figure 4

Environment definition section of an example behavioral experiment input encoding XML. On top, all worm-related information is defined (dark green frame). Within this worm status information, two light green boxes identify the worm mutation (wormData) and the worm's location on the experimentation plate. wormData identifies a one day old female hermaphrodite, at the L1 stage being 1 hour without food. Marked in blue, the experimentation plate configuration defines a cylindrical plate shape (border height: 15 mm; radius: 50 mm), an agar substrate (described as A), the plate dryness (1 mg over the plate's dry weight) and the lack of a lid. The red colored rectangle identifies a cylindrical obstacle (height: 5 mm; radius: 5 mm; stiffness: 43.2 N/m) located at defined distances and angle with respect to the central X and Y axes). The purple frame termed “worm's crowding” defines the number of worms on the plate (one in this case) and their distribution. The latter is represented by an index that points to predefined formulae.

Figure 5

Web-based C. elegans behavioral experiment definition GUI for configuring behavioral input parameters. 3D window (middle), experiment definition window (bottom) and the properties window (right).

Figure 6

Neuron Model Definition Screen.

Figure 7

Neural Network Configuration GUI.

Figure 8

Web-based virtual worm simulation results visualization with behavioral stimuli input. The virtual worm visualization is synchronized with behavioral stimuli at the bottom and can be controlled by sliders on the right-hand side and Play / Pause button.

Figure 9

Web-based virtual worm simulation results visualization with neural traces visualization. The virtual worm visualization is synchronized with the neural activity at the bottom. Parameters can be selected in controls window on the right-hand side, and can be controlled by using the slider on the right-hand side and Play / Pause button.

Figure 10

3D window focused on specific neurons visualization. 3D window with camera set to show a selected neuron (in green), two postsynaptic neurons (in yellow) and all remaining neurons in dark red below the worm's cuticle (almost transparent). This figure was originally presented in Mujika et al. (2015).

Figure 11

Mean ratings of word pairs.

Figure 12

Mean value of all four AttrakDiff dimensions.

Figure 13

Results overview presenting PQ and HQ dimensions and the confidence rectangle.