biophysical model
A data and task-constrained mechanistic model of the mouse outer retina shows robustness to contrast variations
Visual processing starts in the outer retina where photoreceptors transform light into electrochemical signals. These signals are modulated by inhibition from horizontal cells and sent to the inner retina via excitatory bipolar cells. The outer retina is thought to play an important role in contrast invariant coding of visual information, but how the different cell types implement this computation together remains incompletely understood. To understand the role of each cell type, we developed a fully-differentiable biophysical model of a circular patch of mouse outer retina. The model includes 200 cone photoreceptors with a realistic phototransduction cascade and ribbon synapses as well as horizontal and bipolar cells, all with celltype specific ion channels. Going beyond decades of work constraining biophysical models of neurons only by experimental data, we used a dual approach, constraining some parameters of the model with available measurements and others by a visual task: (1) We fit the parameters of the cone models to whole cell patch-clamp measurements of photocurrents and two-photon glutamate imaging measurements of synaptic release.
A data and task-constrained mechanistic model of the mouse outer retina shows robustness to contrast variations
Visual processing starts in the outer retina where photoreceptors transform light into electrochemical signals. These signals are modulated by inhibition from horizontal cells and sent to the inner retina via excitatory bipolar cells. The outer retina is thought to play an important role in contrast invariant coding of visual information, but how the different cell types implement this computation together remains incompletely understood. To understand the role of each cell type, we developed a fully-differentiable biophysical model of a circular patch of mouse outer retina. The model includes 200 cone photoreceptors with a realistic phototransduction cascade and ribbon synapses as well as horizontal and bipolar cells, all with cell-type specific ion channels. Going beyond decades of work constraining biophysical models of neurons only by experimental data, we used a dual approach, constraining some parameters of the model with available measurements and others by a visual task: (1) We fit the parameters of the cone models to whole cell patch-clamp measurements of photocurrents and two-photon glutamate imaging measurements of synaptic release.
Calibrating Biophysical Models for Grape Phenology Prediction via Multi-Task Learning
Solow, William, Saisubramanian, Sandhya
Accurate prediction of grape phenology is essential for timely vineyard management decisions, such as scheduling irrigation and fertilization, to maximize crop yield and quality. While traditional biophysical models calibrated on historical field data can be used for season-long predictions, they lack the precision required for fine-grained vineyard management. Deep learning methods are a compelling alternative but their performance is hindered by sparse phenology datasets, particularly at the cultivar level. We propose a hybrid modeling approach that combines multi-task learning with a recurrent neural network to parameterize a differentiable biophysical model. By using multi-task learning to predict the parameters of the biophysical model, our approach enables shared learning across cultivars while preserving biological structure, thereby improving the robustness and accuracy of predictions. Empirical evaluation using real-world and synthetic datasets demonstrates that our method significantly outperforms both conventional biophysical models and baseline deep learning approaches in predicting phenologi-cal stages, as well as other crop state variables such as cold-hardiness and wheat yield.
Consensus statement on the credibility assessment of ML predictors
Aldieri, Alessandra, Gamage, Thiranja Prasad Babarenda, La Mattina, Antonino Amedeo, Li, Yi, Loewe, Axel, Pappalardo, Francesco, Italy, Marco Viceconti
The rapid integration of machine learning (ML) predictors into in silico medicine has revolutionized the estimation of quantities of interest (QIs) that are otherwise challenging to measure directly. However, the credibility of these predictors is critical, especially when they inform high-stakes healthcare decisions. This position paper presents a consensus statement developed by experts within the In Silico World Community of Practice. We outline twelve key statements forming the theoretical foundation for evaluating the credibility of ML predictors, emphasizing the necessity of causal knowledge, rigorous error quantification, and robustness to biases. By comparing ML predictors with biophysical models, we highlight unique challenges associated with implicit causal knowledge and propose strategies to ensure reliability and applicability. Our recommendations aim to guide researchers, developers, and regulators in the rigorous assessment and deployment of ML predictors in clinical and biomedical contexts.
Hybrid Phenology Modeling for Predicting Temperature Effects on Tree Dormancy
van Bree, Ron, Marcos, Diego, Athanasiadis, Ioannis
Biophysical models offer valuable insights into climate-phenology relationships in both natural and agricultural settings. However, there are substantial structural discrepancies across models which require site-specific recalibration, often yielding inconsistent predictions under similar climate scenarios. Machine learning methods offer data-driven solutions, but often lack interpretability and alignment with existing knowledge. We present a phenology model describing dormancy in fruit trees, integrating conventional biophysical models with a neural network to address their structural disparities. We evaluate our hybrid model in an extensive case study predicting cherry tree phenology in Japan, South Korea and Switzerland. Our approach consistently outperforms both traditional biophysical and machine learning models in predicting blooming dates across years. Additionally, the neural network's adaptability facilitates parameter learning for specific tree varieties, enabling robust generalization to new sites without site-specific recalibration. This hybrid model leverages both biophysical constraints and data-driven flexibility, offering a promising avenue for accurate and interpretable phenology modeling.
Scalable Deep Learning for RNA Secondary Structure Prediction
Franke, Jörg K. H., Runge, Frederic, Hutter, Frank
The field of RNA secondary structure prediction has made significant progress with the adoption of deep learning techniques. In this work, we present the RNAformer, a lean deep learning model using axial attention and recycling in the latent space. We gain performance improvements by designing the architecture for modeling the adjacency matrix directly in the latent space and by scaling the size of the model. Our approach achieves state-of-the-art performance on the popular TS0 benchmark dataset and even outperforms methods that use external information. Further, we show experimentally that the RNAformer can learn a biophysical model of the RNA folding process.
Modelling carbon dioxide emissions under a maize-soy rotation using machine learning
Machine learning (ML) models are an effective and efficient alternative to mechanistic models for predicting CO2 emissions from agricultural soils. Random forest (RF), a classical regression ML model, is a suitable algorithm to predict soil CO2 emissions regardless of fertiliser scenario. Feed-forward neural network (FNN) provides acceptable predictive performance for CO2 emissions, but it does not provide consistent predictive performance in K-Fold cross-validation. Climatic parameters influence CO2 emissions and the complexity of the relationship is not fully captured in biophysical models. Machine learning (ML) is now being applied to environmental problems, and it is, therefore, opportune to investigate ML models in CO2 predictions from agricultural soils.
Machine learning for the diagnosis of early stage diabetes using temporal glucose profiles
Lee, Woo Seok, Jo, Junghyo, Song, Taegeun
Machine learning shows remarkable success for recognizing patterns in data. Here we apply the machine learning (ML) for the diagnosis of early stage diabetes, which is known as a challenging task in medicine. Blood glucose levels are tightly regulated by two counter-regulatory hormones, insulin and glucagon, and the failure of the glucose homeostasis leads to the common metabolic disease, diabetes mellitus. It is a chronic disease that has a long latent period the complicates detection of the disease at an early stage. The vast majority of diabetics result from that diminished effectiveness of insulin action. The insulin resistance must modify the temporal profile of blood glucose. Thus we propose to use ML to detect the subtle change in the temporal pattern of glucose concentration. Time series data of blood glucose with sufficient resolution is currently unavailable, so we confirm the proposal using synthetic data of glucose profiles produced by a biophysical model that considers the glucose regulation and hormone action. Multi-layered perceptrons, convolutional neural networks, and recurrent neural networks all identified the degree of insulin resistance with high accuracy above $85\%$.