Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.04.03.587881

Evaluation and comparison of methods for neuronal parameter optimization using the Neuroptimus software framework

Abstract

Finding optimal parameters for detailed neuronal models is a ubiquitous challenge in neuroscientific research. Recently, manual model tuning has been replaced by automated parameter search using a variety of different tools and methods. However, using most of these software tools and choosing the most appropriate algorithm for a given optimization task require substantial technical expertise, which prevents the majority of researchers from using these methods effectively. To address these issues, we developed a generic platform (called Neuroptimus) that allows users to set up neural parameter optimization tasks via a graphical interface, and to solve these tasks using a wide selection of state-of-the-art parameter search methods implemented by five different Python packages. Neuroptimus also offers several features to support more advanced usage, including the ability to run most algorithms in parallel, which allows it to take advantage of high-performance computing architectures. We used the common interface provided by Neuroptimus to conduct a detailed comparison of more than twenty different algorithms (and implementations) on six distinct benchmarks that represent typical scenarios in neuronal parameter search. We quantified the performance of the algorithms in terms of the best solutions found and in terms of convergence speed. We identified several algorithms, including covariance matrix adaptation evolution strategy and particle swarm optimization, that consistently found good solutions in all of our use cases. By contrast, some other algorithms including all local search methods provided good solutions only for the simplest use cases, and failed completely on more complex problems. Finally, we created an online database that allows uploading, querying and analyzing the results of optimization runs performed by Neuroptimus, which enables all researchers to update and extend the current benchmarking study. The tools and analysis we provide should aid members of the neuroscience community to apply parameter search methods more effectively in their research. Author summaryModel fitting is a widely used method in scientific research. It involves tuning the free parameters of a model until its output best matches the corresponding experimental data. Finding the optimal parameter combination can be a difficult task for more complex models with many unknown parameters, and a large variety of different approaches have been proposed to solve this problem. However, setting up a parameter search task and employing an efficient algorithm for its solution requires considerable technical expertise. We have developed a software framework that helps users solve this task, focusing on the domain of detailed models of single neurons. Our open-source software, called Neuroptimus, has a graphical interface that guides users through the steps of setting up a parameter optimization task, and allows them to select from more than twenty different algorithms to solve the problem. We have also compared the performance of these algorithms on a set of six parameter search tasks that are typical in neuroscience, and identified several algorithms that delivered consistently good performance. Finally, we designed and implemented a website that allows users to view and analyze our results and to add their own results to the database.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mohasci, M., Torok, M. P., Saray, S., Tar, L., Kali, S.. 2024-04-04. Evaluation and comparison of methods for neuronal parameter optimization using the Neuroptimus software framework. https://doi.org/10.1101/2024.04.03.587881

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗