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Biology subjects

Bournes, R.

Publications and source records attributed to Bournes, R..

2 recordsLinked to original sources

Computational model of developmental self-assembly of a cortical microcircuit

Cortical microcircuits emerge from local developmental interactions, yet large-scale computational models typically prescribe connectivity rather than explain its formation. Here we use BioDynaMo to simulate the self-assembly of ~70,000 cortical neurons from 1,200 progenitors in 3D physical space through migration, neurite growth and contact-based synapse formation. With one calibrated filling fraction per connection type, the locally formed synapses reproduce experimentally measured connectivity across 64 connection types (mean absolute error 0.0062) without prescribing individual connections. The grown spiking networks sustain stable, inhibition-dominated activity, and the same developmental rules, given different targets, generate both a canonical cortical microcircuit and a visual-cortex variant. Inverting the migration programme produces a reeler-like column whose aberrant connectivity destabilises network activity. Together, these findings provide a mechanistic link between local developmental processes and the emergence of cortical anatomy, connectivity and function.

neuroscience↗

Open Benchmarking for Cell-Based Multiscale Models: Lessons from a Community Initiative

The emergence of virtual human twins (VHT) in biomedical research has sparked interest in multiscale in silico modelling frameworks, particularly in their application bridging cellular to tissue levels. Among the diverse array of multiscale modelling tools, off-lattice center-based agent-based models (CBM) offer a promising approach due to their depiction of cells in 3D space, closely resembling biological reality. Despite the proliferation of CBM tools addressing various biomedical challenges, a comprehensive and systematic comparison among them has been elusive. This paper presents a community-driven benchmark initiative aimed at evaluating and comparing CBM for biomedical applications, akin to successful efforts in other scientific domains such as the Critical Assessment of Protein Structure Prediction (CASP). Enlisting developers from leading tools like BioDynaMo, Chaste, PhysiCell,TiSim, and CompuTiX, we devised a benchmark scope, defined metrics, and established reference datasets to ensure a meaningful and equitable evaluation. Unit tests targeting different solvers within these tools were designed, ranging from diffusion and mechanics to cell cycle simulations and growth scenarios. Results from these tests demonstrate varying tool implementations in handling diffusion, mechanics, and cell cycle equations, emphasising the need for standardised benchmarks and interoperability. Discussions among the community underscore the necessity for defining gold standards, fostering interoperability, and drawing lessons from analogous benchmarking experiences. The outcomes, disseminated through a public platform in collaboration with OpenEBench, aim to catalyse advancements in computational biology, offering a comprehensive resource for tool evaluation and guiding future developments in cell-level simulations. This initiative endeavours to strengthen and expand the computational biology simulation community through continued dissemination and performance-oriented benchmarking efforts to enable the use of VHT in biomedicine.

systems biology↗