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Matteo Pariset

Publications and source records attributed to Matteo Pariset.

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AI-powered virtual tissues from spatial proteomics for clinical diagnostics and biomedical discovery

Spatial proteomics technologies have transformed our understanding of complex tissue architecture in cancer but present unique challenges for computational analysis. Each study uses a different marker panel and protocol, and most methods are tailored to single cohorts, which limits knowledge transfer and robust biomarker discovery. Here we present Virtual Tissues (VirTues), a general-purpose foundation model for spatial proteomics that learns marker-aware, multi-scale representations of proteins, cells, niches and tissues directly from multiplex imaging data. From a single pretrained backbone, VirTues supports marker reconstruction, cell typing and niche annotation, spatial biomarker discovery, and patient stratification, including zero-shot annotation across heterogeneous panels and datasets. In triple-negative breast cancer, VirTues-derived biomarkers predict anti-PD-L1 chemo-immunotherapy response and stratify disease-free survival in an independent cohort, outperforming state-of-the-art biomarkers derived from the same datasets and current clinical stratification schemes.

q-bio.QM

Unbalanced Diffusion Schr\"odinger Bridge

Schr\"odinger bridges (SBs) provide an elegant framework for modeling the temporal evolution of populations in physical, chemical, or biological systems. Such natural processes are commonly subject to changes in population size over time due to the emergence of new species or birth and death events. However, existing neural parameterizations of SBs such as diffusion Schr\"odinger bridges (DSBs) are restricted to settings in which the endpoints of the stochastic process are both probability measures and assume conservation of mass constraints. To address this limitation, we introduce unbalanced DSBs which model the temporal evolution of marginals with arbitrary finite mass. This is achieved by deriving the time reversal of stochastic differential equations with killing and birth terms. We present two novel algorithmic schemes that comprise a scalable objective function for training unbalanced DSBs and provide a theoretical analysis alongside challenging applications on predicting heterogeneous molecular single-cell responses to various cancer drugs and simulating the emergence and spread of new viral variants.

cs.LG

Aligned Diffusion Schr\"odinger Bridges

Diffusion Schr\"odinger bridges (DSB) have recently emerged as a powerful framework for recovering stochastic dynamics via their marginal observations at different time points. Despite numerous successful applications, existing algorithms for solving DSBs have so far failed to utilize the structure of aligned data, which naturally arises in many biological phenomena. In this paper, we propose a novel algorithmic framework that, for the first time, solves DSBs while respecting the data alignment. Our approach hinges on a combination of two decades-old ideas: The classical Schr\"odinger bridge theory and Doob's $h$-transform. Compared to prior methods, our approach leads to a simpler training procedure with lower variance, which we further augment with principled regularization schemes. This ultimately leads to sizeable improvements across experiments on synthetic and real data, including the tasks of predicting conformational changes in proteins and temporal evolution of cellular differentiation processes.

cs.LG