Joana B. Pereira – Soft Matter Lab

Mapping individual molecular connectomes in Alzheimer’s disease published in Alzheimer’s & Dementia

Diagnostic classification. *(Image from the article.)*

Mapping individual molecular connectomes in Alzheimer’s disease
Zhilei Xu, Mite Mijalkov, Jiawei Sun, Yu-Wei Chang, Arianna Sala, Giovanni Volpe, Mario Severino, Mattia Veronese, Sara Garcia-Ptacek, Joana B. Pereira, for the Alzheimer’s Disease Neuroimaging Initiative
Alzheimer’s & Dementia 22, e71310 (2026)
DOI: 10.1002/alz.71310

INTRODUCTION
Mapping individual differences is crucial to improve personalized medicine approaches in Alzheimer’s disease (AD), which is characterized by strong inter-individual variability in the accumulation patterns of tau and amyloid beta pathology.

METHODS
We assess the progression of AD across the disease continuum by building individual molecular connectomes using longitudinal positron emission tomography (PET) data.

RESULTS
We demonstrate that these connectomes constitute a unique fingerprint, capable of identifying a single individual from a large group of subjects. Alterations in the connectomes discriminate different diagnostic groups and predict cognitive decline to a higher extent than conventional PET measures. We introduce a novel gene-specific transcription network analysis that linked individual tau and amyloid connectomes to a common transcriptomic profile of apoptosis, with the tau connectome being specifically related to pyrimidine metabolism, and the amyloid connectome to histone acetylation.

DISCUSSION
Individual molecular connectome mapping provides a novel and sensitive framework to monitor AD progression.

Highlights

Individual molecular connectomes constitute a unique fingerprint, capable of identifying a single individual from a large group of subjects.
Alterations in individual molecular connectomes significantly increase both across the Alzheimer’s disease (AD) continuum and over time.
Alterations in individual molecular connectomes discriminate different diagnostic groups and predict cognitive decline to a higher extent than conventional positron emission tomography measures.
Susceptibilities of individual tau and amyloid connectomes to AD are linked to a common transcriptomic profile of apoptosis, with the tau connectome being specifically related to pyrimidine metabolism, and the amyloid connectome to histone acetylation.

Tracking early cognitive decline in preclinical AD with brain MRI similarity published in Alzheimer’s & Dementia

Parcellation of the brain cortex. *(Image from the article.)*

Tracking early cognitive decline in preclinical AD with brain MRI similarity
Jiawei Sun, Blanca Zufiria-Gerbolés, Massimiliano Passaretti, Giovanni Volpe, Mite Mijalkov, Joana B. Pereira, for the Alzheimer’s Disease Neuroimaging Initiative
Alzheimer’s & Dementia 22, e71170 (2026)
DOI: 10.1002/alz.71170

INTRODUCTION
Early detection of neuroanatomical changes in preclinical Alzheimer’s disease (AD) is critical for timely intervention. However, conventional magnetic resonance imaging (MRI) and fluid biomarkers often lack sensitivity to subtle structural alterations in early disease stages.

METHODS
To identify early brain alterations, we applied a perturbation-based brain similarity approach to cognitively normal participants from Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Open Access Series of Imaging Studies (OASIS), stratified by amyloid status. We evaluated its predictive performance for cognition and diagnostic conversion against cortical thickness, volumetric MRI, and fluid biomarkers.

RESULTS
In both cohorts, brain similarity consistently outperformed other biomarkers across cognitive domains and amyloid groups. It also achieved superior accuracy in predicting clinical conversion and exhibited associations with cytoarchitectural organization.

DISCUSSION
These findings highlight brain similarity as a sensitive marker of early neuroanatomical disruption in AD. Its ability to detect subtle structural changes before overt atrophy underscores its potential for early disease monitoring and treatment assessment in preclinical AD trials.

Highlights

Brain similarity captures early brain changes in preclinical Alzheimer’s disease (AD).
Brain similarity outperforms conventional biomarkers such as cortical thickness, volume measures, and fluid biomarkers in predicting cognitive decline.
Brain similarity predicts conversion to mild cognitive impairment and AD more accurately than traditional imaging markers, and its predictive performance is further improved when combined with fluid biomarkers.
Brain similarity captures structural disruptions associated with cortical layer II of the cytoarchitectonic lamina of human neocortex.

International conference “Protein Folding in Real Time: From Molecules to Disease”, Aula Medica, KI, Stockholm, 11-13 March 2026

Giovanni Volpe opens the Protein Folding in Real Time conference. *(Photo by A. Ciarlo)*

The international conference Protein Folding in Real Time: From Molecules to Disease opened today, 11 March 2026, at Aula Medica, KI, Stockholm.

The conference brings together researchers from multiple disciplines, including biophysics, molecular biology, computational science, and medicine, to discuss recent advances in the study of protein folding. Proteins must fold into precise three-dimensional structures to perform their biological functions, and failures in this process are associated with several diseases, including neurodegenerative disorders and cancer.

During the three-day meeting, participants attend a series of lectures and discussions covering topics such as single-molecule biophysics, high-resolution experimental techniques for observing folding dynamics, advanced molecular simulations, and artificial intelligence approaches for predicting folding pathways. Particular attention is given to the challenge of observing protein folding in real time, capturing transient intermediate states that determine whether proteins reach their functional structure or misfold.

The event also highlights the interdisciplinary and international nature of the initiative. Representatives from the Embassies of Italy, Japan, and Spain, together with UNESCO, take part in the meeting, emphasizing the global interest in advancing research on protein folding and its biomedical implications. The initiative aims to integrate experimental measurements, computational modeling, and data-driven approaches to build a predictive framework for protein folding dynamics. By combining advanced imaging, force spectroscopy, and machine learning methods, the initiative seeks to better understand how folding processes occur inside living systems and how their disruption can lead to disease.

Overall, the conference provides an opportunity for scientists from different institutions to exchange ideas, establish collaborations, and shape future research directions in the field of protein folding and misfolding. The launch of this initiative represents an important step toward bridging molecular-level observations with biomedical applications, ultimately contributing to improved strategies for diagnosing and treating diseases related to protein misfolding.

Technological Excellence Requires Human and Social Context on ArXiv

Why breakthrough research needs humanities and social sciences. *(From an artwork by Jacopo Sacquegno.)*

Technological Excellence Requires Human and Social Context
Karl Palmås, Mats Benner, Monica Billger, Ben Clarke, Raimund Feifel, Julia Fernandez-Rodriguez, Anna Foka, Juliette Griffié, Claes Gustafsson, Kerstin Hamilton, Johan Holmén, Kristina Lindström, Tobias Olofsson, Joana B. Pereira, Marisa Ponti, Julia Ravanis, Sviatlana Shashkova, Emma Sparr, Pontus Strimling, Fredrik Höök, Giovanni Volpe
arXiv: 2603.10653

Breakthrough technologies increasingly shape social institutions, economic systems, and political futures. Yet models of research excellence associated with such technologies often prioritize technical performance, scalability, and short-term innovation metrics while treating ethical, social, and cultural dimensions as secondary considerations. This perspective article argues that such separation is no longer tenable. We propose a broader understanding of excellence that combines technical rigor with ethical robustness, social intelligibility, and long-term relevance. The rapid emergence of generative and agentic artificial intelligence further underscores this argument. As technological systems increasingly operate through language, interpretation, and normative alignment, expertise traditionally cultivated in the humanities and social sciences becomes integral to the design, governance, and responsible deployment of such systems. Drawing on historical examples and contemporary research practices, this article examines five interconnected domains where the humanities and social sciences, treated as integrated dimensions of research practice, can strengthen technological development: (1) ethical, legal, and social integration in agenda-setting and research design; (2) plural and reflexive foresight practices that shape technological futures; (3) graduate education as a leverage point for cross-disciplinary literacy; (4) visualization and communication as epistemic and civic practices; and (5) institutional frameworks that move beyond rigid distinctions between basic and applied research. Across these dimensions, we propose practical strategies for embedding interdisciplinary collaboration structurally rather than symbolically.

Roadmap on Deep Learning for Microscopy published in Journal of Physics: Photonics

Spatio-temporal spectrum diagram of microscopy techniques and their applications. *(Image by the Authors of the manuscript.)*

Roadmap on Deep Learning for Microscopy
Giovanni Volpe, Carolina Wählby, Lei Tian, Michael Hecht, Artur Yakimovich, Kristina Monakhova, Laura Waller, Ivo F. Sbalzarini, Christopher A. Metzler, Mingyang Xie, Kevin Zhang, Isaac C.D. Lenton, Halina Rubinsztein-Dunlop, Daniel Brunner, Bijie Bai, Aydogan Ozcan, Daniel Midtvedt, Hao Wang, Nataša Sladoje, Joakim Lindblad, Jason T. Smith, Marien Ochoa, Margarida Barroso, Xavier Intes, Tong Qiu, Li-Yu Yu, Sixian You, Yongtao Liu, Maxim A. Ziatdinov, Sergei V. Kalinin, Arlo Sheridan, Uri Manor, Elias Nehme, Ofri Goldenberg, Yoav Shechtman, Henrik K. Moberg, Christoph Langhammer, Barbora Špačková, Saga Helgadottir, Benjamin Midtvedt, Aykut Argun, Tobias Thalheim, Frank Cichos, Stefano Bo, Lars Hubatsch, Jesus Pineda, Carlo Manzo, Harshith Bachimanchi, Erik Selander, Antoni Homs-Corbera, Martin Fränzl, Kevin de Haan, Yair Rivenson, Zofia Korczak, Caroline Beck Adiels, Mite Mijalkov, Dániel Veréb, Yu-Wei Chang, Joana B. Pereira, Damian Matuszewski, Gustaf Kylberg, Ida-Maria Sintorn, Juan C. Caicedo, Beth A Cimini, Muyinatu A. Lediju Bell, Bruno M. Saraiva, Guillaume Jacquemet, Ricardo Henriques, Wei Ouyang, Trang Le, Estibaliz Gómez-de-Mariscal, Daniel Sage, Arrate Muñoz-Barrutia, Ebba Josefson Lindqvist, Johanna Bergman
Journal of Physics: Photonics 8, 012501 (2026)
arXiv: 2303.03793
doi: 10.1088/2515-7647/ae0fd1

Through digital imaging, microscopy has evolved from primarily being a means for visual observation of life at the micro- and nano-scale, to a quantitative tool with ever-increasing resolution and throughput. Artificial intelligence, deep neural networks, and machine learning (ML) are all niche terms describing computational methods that have gained a pivotal role in microscopy-based research over the past decade. This Roadmap encompasses key aspects of how ML is applied to microscopy image data, with the aim of gaining scientific knowledge by improved image quality, automated detection, segmentation, classification and tracking of objects, and efficient merging of information from multiple imaging modalities. We aim to give the reader an overview of the key developments and an understanding of possibilities and limitations of ML for microscopy. It will be of interest to a wide cross-disciplinary audience in the physical sciences and life sciences.

Deep-Learning Investigation of Vibrational Raman Spectra for Plant-Stress Analysis on ArXiv

In this work, we present an unsupervised deep learning framework using Variational Autoencoders (VAEs) to decode stress-specific biomolecular fingerprints directly from Raman spectral data across multiple plant species and genotypes. *(Image by the Authors of the manuscript. A part of the image was designed using Biorender.com.)*

From Spectra to Stress: Unsupervised Deep Learning for Plant Health Monitoring
Anoop C. Patil, Benny Jian Rong Sng, Yu-Wei Chang, Joana B. Pereira, Chua Nam-Hai, Rajani Sarojam, Gajendra Pratap Singh, In-Cheol Jang, and Giovanni Volpe
ArXiv: 2507.15772

Detecting stress in plants is crucial for both open-farm and controlled-environment agriculture. Biomolecules within plants serve as key stress indicators, offering vital markers for continuous health monitoring and early disease detection. Raman spectroscopy provides a powerful, non-invasive means to quantify these biomolecules through their molecular vibrational signatures. However, traditional Raman analysis relies on customized data-processing workflows that require fluorescence background removal and prior identification of Raman peaks of interest-introducing potential biases and inconsistencies. Here, we introduce DIVA (Deep-learning-based Investigation of Vibrational Raman spectra for plant-stress Analysis), a fully automated workflow based on a variational autoencoder. Unlike conventional approaches, DIVA processes native Raman spectra-including fluorescence backgrounds-without manual preprocessing, identifying and quantifying significant spectral features in an unbiased manner. We applied DIVA to detect a range of plant stresses, including abiotic (shading, high light intensity, high temperature) and biotic stressors (bacterial infections). By integrating deep learning with vibrational spectroscopy, DIVA paves the way for AI-driven plant health assessment, fostering more resilient and sustainable agricultural practices.

BRAPH 2: a flexible, open-source, reproducible, community-oriented, easy-to-use framework for network analyses in neurosciences on bioRxiv

BRAPH 2 Genesis enables swift creation of custom, reproducible software distributions—tackling the growing complexity of neuroscience by streamlining analysis across diverse data types and workflows. *(Image by B. Zufiria-Gerbolés and Y.-W. Chang.)*

BRAPH 2: a flexible, open-source, reproducible, community-oriented, easy-to-use framework for network analyses in neurosciences
Yu-Wei Chang, Blanca Zufiria-Gerbolés, Pablo Emiliano Gómez-Ruiz, Anna Canal-Garcia, Hang Zhao, Mite Mijalkov, Joana Braga Pereira, Giovanni Volpe
bioRxiv: 10.1101/2025.04.11.648455

As network analyses in neuroscience continue to grow in both complexity and size, flexible methods are urgently needed to provide unbiased, reproducible insights into brain function. BRAPH 2 is a versatile, open-source framework that meets this challenge by offering streamlined workflows for advanced statistical models and deep learning in a community-oriented environment. Through its Genesis compiler, users can build specialized distributions with custom pipelines, ensuring flexibility and scalability across diverse research domains. These powerful capabilities will ensure reproducibility and accelerate discoveries in neuroscience.

Computational memory capacity predicts aging and cognitive decline published in Nature Communications

Memory capacity in aging. A Brain reservoir computing architecture with uniform random signals applied to all nodes. *(Image from the article.)*

Computational memory capacity predicts aging and cognitive decline
Mite Mijalkov, Ludvig Storm, Blanca Zufiria-Gerbolés, Dániel Veréb, Zhilei Xu, Anna Canal-Garcia, Jiawei Sun, Yu-Wei Chang, Hang Zhao, Emiliano Gómez-Ruiz, Massimiliano Passaretti, Sara Garcia-Ptacek, Miia Kivipelto, Per Svenningsson, Henrik Zetterberg, Heidi Jacobs, Kathy Lüdge, Daniel Brunner, Bernhard Mehlig, Giovanni Volpe, Joana B. Pereira
Nature Communications 16, 2748 (2025)
doi: 10.1038/s41467-025-57995-0

Memory is a crucial cognitive function that deteriorates with age. However, this ability is normally assessed using cognitive tests instead of the architecture of brain networks. Here, we use reservoir computing, a recurrent neural network computing paradigm, to assess the linear memory capacities of neural-network reservoirs extracted from brain anatomical connectivity data in a lifespan cohort of 636 individuals. The computational memory capacity emerges as a robust marker of aging, being associated with resting-state functional activity, white matter integrity, locus coeruleus signal intensity, and cognitive performance. We replicate our findings in an independent cohort of 154 young and 72 old individuals. By linking the computational memory capacity of the brain network with cognition, brain function and integrity, our findings open new pathways to employ reservoir computing to investigate aging and age-related disorders.

Global graph features unveiled by unsupervised geometric deep learning on ArXiv

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, Joana B. Pereira, Carlo Manzo, Giovanni Volpe
arXiv: 2503.05560

Graphs provide a powerful framework for modeling complex systems, but their structural variability makes analysis and classification challenging. To address this, we introduce GAUDI (Graph Autoencoder Uncovering Descriptive Information), a novel unsupervised geometric deep learning framework that captures both local details and global structure. GAUDI employs an innovative hourglass architecture with hierarchical pooling and upsampling layers, linked through skip connections to preserve essential connectivity information throughout the encoding-decoding process. By mapping different realizations of a system – generated from the same underlying parameters – into a continuous, structured latent space, GAUDI disentangles invariant process-level features from stochastic noise. We demonstrate its power across multiple applications, including modeling small-world networks, characterizing protein assemblies from super-resolution microscopy, analyzing collective motion in the Vicsek model, and capturing age-related changes in brain connectivity. This approach not only improves the analysis of complex graphs but also provides new insights into emergent phenomena across diverse scientific domains.

Book “Deep Learning Crash Course” published at No Starch Press

The book Deep Learning Crash Course, authored by Giovanni Volpe, Benjamin Midtvedt, Jesús Pineda, Henrik Klein Moberg, Harshith Bachimanchi, Joana B. Pereira, and Carlo Manzo, has been published online by No Starch Press in July 2024.

Preorder Discount
A preorder discount is available: preorders with coupon code PREORDER will receive 25% off. Link: Preorder @ No Starch Press | Deep Learning Crash Course

Links
@ No Starch Press

Citation
Giovanni Volpe, Benjamin Midtvedt, Jesús Pineda, Henrik Klein Moberg, Harshith Bachimanchi, Joana B. Pereira, and Carlo Manzo. Deep Learning Crash Course. No Starch Press.
ISBN-13: 9781718503922