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Presentation by J. Pineda at LoG Meetup Sweden, 12 February 2025

MIRO employs a recurrent graph neural network to refine SMLM point clouds by compressing clusters around their center, enhancing inter-cluster distinction and background separation for efficient clustering. (Image by J. Pineda.)
Relational Inductive Biases as a Key to Smarter Deep Learning Microscopy
Jesús Pineda
Learning on graphs and geometry meetup at Uppsala University
Date: 12 February 2025
Time: 11:15
Place: Lecture hall 4101, Ångströmlaboratoriet, Uppsala, Sweden

Geometric deep learning has revolutionized fields like social network analysis, molecular chemistry, and neuroscience, but its application to microscopy data analysis remains a significant challenge. The hurdles stem not only from the scarcity of high-quality data but also from the intrinsic complexity and variability of microscopy datasets. This presentation introduces two groundbreaking geometric deep-learning frameworks designed to overcome these barriers, advancing the integration of graph neural networks (GNNs) into microscopy and unlocking their full potential. First, we present MAGIK, a cutting-edge framework for analyzing biological system dynamics through time-lapse microscopy. Leveraging a graph neural network augmented with attention-based mechanisms, MAGIK processes object features using geometric priors. This enables it to perform a range of tasks, from linking coordinates into trajectories to uncovering local and global dynamic properties with unprecedented precision. Remarkably, MAGIK excels under minimal data conditions, maintaining exceptional performance and robust generalization across diverse scenarios. Next, we introduce MIRO, a novel algorithm powered by recurrent graph neural networks. MIRO pre-processes Single Molecule Localization (SML) datasets to enhance the efficiency of conventional clustering methods. Its ability to handle clusters of varying shapes and scales enables more accurate and consistent analyses across complex datasets. Furthermore, MIRO’s single- and few-shot learning capabilities allow it to generalize effortlessly across scenarios, making it an efficient, scalable, and versatile tool for microscopy data analysis. Together, MAGIK and MIRO address critical limitations in microscopy data analysis, offering innovative solutions for multi-scale data analysis and advancing the boundaries of what is currently achievable with geometric deep learning in the field.

Reference

Pineda, Jesús, Benjamin Midtvedt, Harshith Bachimanchi, Sergio Noé, Daniel Midtvedt, Giovanni Volpe, and Carlo Manzo. Geometric deep learning reveals the spatiotemporal features of microscopic motionNat Mach Intell 5, 71–82 (2023).

Pineda, Jesús, Sergi Masó-Orriols, Joan Bertran, Mattias Goksör, Giovanni Volpe, and Carlo Manzo. Spatial Clustering of Molecular Localizations with Graph Neural Networks.  arXiv: 2412.00173 (2024).

Poster by M. Granfors at the Learning on graphs and geometry meetup in Uppsala, 11 February 2025

GAUDI leverages a hierarchical graph-convolutional variational autoencoder architecture, where an encoder progressively compresses the graph into a low-dimensional latent space, and a decoder reconstructs the graph from the latent embedding. (Image by M. Granfors and J. Pineda.)
Global graph features unveiled by unsupervised geometric deep learning
Mirja Granfors, Jesús Pineda, Blanca Zufiria Gerbolés, Daniel Vereb, Joana B. Pereira, Carlo Manzo, and Giovanni Volpe
Learning on graphs and geometry meetup at Uppsala University
Date: 11 February 2025
Place: Uppsala university

Graphs are used to model complex relationships, such as interactions between particles or connections between brain regions. The structural complexity and variability of graphs pose challenges to their efficient analysis and classification. Here, we propose GAUDI (Graph Autoencoder Uncovering Descriptive Information), a graph autoencoder that addresses these challenges. GAUDI’s encoder progressively reduces the size of the graph using multi-step hierarchical pooling, while its decoder incrementally increases the graph size until the original dimensions are restored, focusing on the node and edge features while preserving the graph structure through skip-connections. By training GAUDI to minimize the difference between the node and edge features of the input graph and those of the output graph, it is compelled to capture the most critical parameters describing these features in the latent space, thereby enabling the extraction of essential parameters characterizing the graphs. We demonstrate the performance of GAUDI across diverse graph data originating from complex systems, including the estimation of the parameters of Watts-Strogatz graphs, the classification of protein assembly structures from single-molecule localization microscopy data, the analysis of collective behaviors, and correlations between brain connections and age. This approach offers a robust framework for efficiently analyzing and interpreting complex graph data, facilitating the extraction of meaningful patterns and insights across a wide range of applications.

Invited talk by J. Pineda at the CMCB Lab on 27 January 2025

MIRO employs a recurrent graph neural network to refine SMLM point clouds by compressing clusters around their center, enhancing inter-cluster distinction and background separation for efficient clustering. (Image by J. Pineda.)
Spatial clustering of molecular localizations with graph neural networks
Jesús Pineda
Date: 27 January 2025
Time: 10:00
Place: SciLifeLab Campus Solna, Sweden

Single-molecule localization microscopy (SMLM) generates point clouds corresponding to fluorophore localizations. Spatial cluster identification and analysis of these point clouds are crucial for extracting insights about molecular organization. However, this task becomes challenging in the presence of localization noise, high point density, or complex biological structures. Here, we introduce MIRO (Multimodal Integration through Relational Optimization), an algorithm that uses recurrent graph neural networks to transform the point clouds in order to improve clustering efficiency when applying conventional clustering techniques. We show that MIRO supports simultaneous processing of clusters of different shapes and at multiple scales, demonstrating improved performance across varied datasets. Our comprehensive evaluation demonstrates MIRO’s transformative potential for single-molecule localization applications, showcasing its capability to revolutionize cluster analysis and provide accurate, reliable details of molecular architecture. In addition, MIRO’s robust clustering capabilities hold promise for applications in various fields such as neuroscience, for the analysis of neural connectivity patterns, and environmental science, for studying spatial distributions of ecological data.

Reference
Pineda, Jesús, Sergi Masó-Orriols, Joan Bertran, Mattias Goksör, Giovanni Volpe, and Carlo Manzo. Spatial Clustering of Molecular Localizations with Graph Neural Networks.  arXiv: 2412.00173

Gan Wang will defend his PhD thesis on 20 January 2025.

Gan Wang, PhD defense.
(Photo by A. Ciarlo.)
Gan Wang will defend his PhD thesis on 20 January 2025. The defense will take place in PJ, Institutionen för fysik, Origovägen 6b, Göteborg, at 10:00.

Title: Microfabrication technique applications: from passive particle manipulation to active microswimmers, micromachines, and fluidic control

Abstract: Overcoming Brownian motion at the micro- and nanoscale to achieve precise control of objects is crucial for fields such as materials science and biology. Significant progress has been made in trapping and manipulating micro- and nanoscale objects, either by generating gradients through external physical fields or by engineering systems that can harvest energy from their environment for autonomous motion. These techniques rely on the precise application of forces, such as optical and electromagnetic forces, and have found extensive applications across various scientific disciplines. Recent advances in micro- and nanofabrication technologies have greatly enhanced the generation and regulation of these forces, offering new possibilities for manipulating micro- and nanoscale objects.

This thesis applies traditional micro- and nanofabrication techniques, typically used in semiconductor manufacturing, to construct micro- and nanostructures for manipulating forces, primarily critical Casimir forces and optical forces, to achieve precise control over microscale object movement.

I first show the fabrication of periodic micropatterns on a substrate, followed by chemical functionalization to impart hydrophilic and hydrophobic properties. Near the critical temperature of a binary liquid, attractive and repulsive critical Casimir forces are generated between the micropatterns and microparticles. These forces allow the stable trapping of the microparticles on the substrate and the manipulation of their configuration and movement.
Then, my research transitions from passive control to active motion by fabricating metasurfaces capable of modulating optical fields and embedding them within micro-particles (microswimmers). This enables light-momentum exchange under planar laser illumination, resulting in autonomous movement of the microswimmers. By varying the metasurface design as well as the intensity and polarization of the light, complex behaviors can emerge within these microswimmers. Subsequently, My research focused on using these microfabrication techniques to build micromotors integrated on a chip surface. These micromotors couple with other objects through gear structures, creating miniature machines that can execute functional tasks. Finally, by altering the configuration of these machines and the distances between them, I acheived precise, multifunctional control over fluid dynamics, facilitating the transport of micro- and nanoscale objects.

Insights gained from this research suggest innovative manufacturing approaches for scalable manipulation of particles, more intelligent microrobots, and powerful miniaturized on-chip machines, with applications across various fields.

Thesis: https://hdl.handle.net/2077/84048

Supervisor: Giovanni Volpe
Examiner: Dag Hanstorp
Opponent: Peer Fischer
Committee: Heiner Linke, Anna Maciolek, Hao Zeng
Alternate board member: Francesco Ferranti

Diffusion models for super-resolution microscopy: a tutorial published in Journal of Physics: Photonics

Super-resolution by diffusion models: low-resolution images of microtubules (left) are transformed to high-resolution (right) by diffusion model. Dataset courtesy: BioSR Dataset. (Image by H. Bachimamchi.)
Diffusion models for super-resolution microscopy: a tutorial
Harshith Bachimanchi, Giovanni Volpe
Journal of Physics: Photonics 7, 013001 (2025)
doi: 10.1088/2515-7647/ada101
arXiv: 2409.16488

Diffusion models have emerged as a prominent technique in generative modeling with neural networks, making their mark in tasks like text-to-image translation and super-resolution. In this tutorial, we provide a comprehensive guide to build denoising diffusion probabilistic models from scratch, with a specific focus on transforming low-resolution microscopy images into their corresponding high-resolution versions in the context of super-resolution microscopy. We provide the necessary theoretical background, the essential mathematical derivations, and a detailed Python code implementation using PyTorch. We discuss the metrics to quantitatively evaluate the model, illustrate the model performance at different noise levels of the input low-resolution images, and briefly discuss how to adapt the tutorial for other applications. The code provided in this tutorial is also available as a Python notebook in the supplementary information.

Talk by Ivo Sbalzarini, 9 January 2025

Ivo Sbalzarini, talk. (Photo by Y.-W. Chang.)
Content-adaptive deep learning for large-scale
fluorescence microscopy imaging

Ivo Sbalzarini
Max Planck Institute of Molecular Cell Biology and Genetics
Center for Systems Biology Dresden
https://sbalzarini-lab.org/

Date: 9 January 2025
Time: 11:00
Place: Nexus

Anqi Lyu joins the Soft Matter Lab

Anqi Lyu starts her PhD at the Physics Department of the University of Gothenburg on 8 January 2025.

Anqi has a Master degree in Medical Bioinformatics from University of Verona, Italy.

In her PhD, she will focus on delineating how plasma factors globally influence endothelial cells, with emphasis on their roles in health, ageing and disease, by utilizing computational tools in combination with interdisciplinary approaches.

Benjamin Midtvedt defended his PhD thesis on 9 January 2025. Congrats!

Benjamin Midtvedt, PhD defense. (Photo by H. P. Thanabalan.)
Benjamin Midtvedt defended his PhD thesis on 9 January 2025. The defense will take place in PJ, Institutionen för fysik, Origovägen 6b, Göteborg, at 13:00. Congrats!

Title: Annotation-free deep learning for quantitative microscopy

Abstract: Quantitative microscopy is an essential tool for studying and understanding microscopic structures. However, analyzing the large and complex datasets generated by modern microscopes presents significant challenges. Manual analysis is time-intensive and subjective, rendering it impractical for large datasets. While automated algorithms offer faster and more consistent results, they often require careful parameter tuning to achieve acceptable performance, and struggle to interpret the more complex data produced by modern microscopes. As such, there is a pressing need to develop new, scalable analysis methods for quantitative microscopy. In recent years, deep learning has transformed the field of computer vision, achieving superhuman performance in tasks ranging from image classification to object detection. However, this success depends on large, annotated datasets, which are often unavailable in microscopy. As such, to successfully and efficiently apply deep learning to microscopy, new strategies that bypass the dependency on extensive annotations are required. In this dissertation, I aim to lower the barrier for applying deep learning in microscopy by developing methods that do not rely on manual annotations and by providing resources to assist researchers in using deep learning to analyze their own microscopy data. First, I present two cases where training annotations are generated through alternative means that bypass the need for human effort. Second, I introduce a deep learning method that leverages symmetries in both the data and the task structure to train a statistically optimal model for object detection without any annotations. Third, I propose a method based on contrastive learning to estimate nanoparticle sizes in diffraction-limited microscopy images, without requiring annotations or prior knowledge of the optical system. Finally, I deliver a suite of resources that empower researchers in applying deep learning to microscopy. Through these developments, I aim to demonstrate that deep learning is not merely a “black box” tool. Instead, effective deep learning models should be designed with careful consideration of the data, assumptions, task structure, and model architecture, encoding as much prior knowledge as possible. By structuring these interactions with care, we can develop models that are more efficient, interpretable, and generalizable, enabling them to tackle a wider range of microscopy tasks.

Thesis: https://hdl.handle.net/2077/84178

Supervisor: Giovanni Volpe
Examiner: Dag Hanstorp
Opponent: Ivo Sbalzarini
Committee: Susan Cox, Maria Arrate Munoz Barrutia, Ignacio Arganda-Carreras
Alternate board member: Måns Henningson

Ivo Sbalzarini (left) and Benjamin Midtvedt (right). (Photo by H. P. Thanabalan.)
Benjamin Midtvedt (left), Giovanni Volpe (right), announcement. (Photo by H. P. Thanabalan.)
From left to right: Ignacio Arganda, Arrate Muñoz Barrutia, Susan Cox, Benjamin Midtvedt, Giovanni Volpe, Ivo Sbalzarini. (Photo by H. P. Thanabalan.)

Roadmap on machine learning glassy dynamics published in Nature Review Physics

Visual summary of the scope of the review. (Image by the Authors.)
Roadmap on machine learning glassy dynamics
Gerhard Jung, Rinske M. Alkemade, Victor Bapst, Daniele Coslovich, Laura Filion, François P. Landes, Andrea J. Liu, Francesco Saverio Pezzicoli, Hayato Shiba, Giovanni Volpe, Francesco Zamponi, Ludovic Berthier & Giulio Biroli
Nature Review Physics (2025)
doi: 10.1038/s42254-024-00791-4
arxiv: 2311.14752

Unravelling the connections between microscopic structure, emergent physical properties and slow dynamics has long been a challenge when studying the glass transition. The absence of clear visible structural order in amorphous configurations complicates the identification of the key physical mechanisms underpinning slow dynamics. The difficulty in sampling equilibrated configurations at low temperatures hampers thorough numerical and theoretical investigations. We explore the potential of machine learning (ML) techniques to face these challenges, building on the algorithms that have revolutionized computer vision and image recognition. We present both successful ML applications and open problems for the future, such as transferability and interpretability of ML approaches. To foster a collaborative community effort, we also highlight the ‘GlassBench’ dataset, which provides simulation data and benchmarks for both 2D and 3D glass formers. We compare the performance of emerging ML methodologies, in line with benchmarking practices in image and text recognition. Our goal is to provide guidelines for the development of ML techniques in systems displaying slow dynamics and inspire new directions to improve our theoretical understanding of glassy liquids.

Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity published in Nature Communications

Brain region connectivity. (Image by the Authors of the manuscript.)
Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity
Shuyang Yao, Arvid Harder, Fahimeh Darki, Yu-Wei Chang , Ang Li, Kasra Nikouei, Giovanni Volpe, Johan N Lundström, Jian Zeng , Naomi Wray, Yi Lu, Patrick F Sullivan, Jens Hjerling-Leffler
Nature Communications 16, 395 (2025)
doi: 10.1038/s41467-024-55611-1
medRxiv: 10.1101/2024.01.18.24301478

Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability. Using functional MRI connectivity, we further confirmed the significance of the central and lateral amygdala, hippocampal body, and prefrontal cortex in distinguishing schizophrenia cases from controls. Our findings underscore the value of single-cell transcriptomics in understanding the polygenicity of psychiatric disorders and suggest a promising alignment of genomic, transcriptomic, and brain imaging modalities for identifying common biological targets.