Jovan Tanevski

Arezou Rahimi, Luis A. Vale-Silva, Maria Faelth Savitski et al.

Single-cell RNA sequencing (scRNA-seq) and spatially-resolved imaging/sequencing technologies have revolutionized biomedical research. On one hand, scRNA-seq provides information about a large portion of the transcriptome for individual cells, but lacks the spatial context. On the other hand, spatially-resolved measurements come with a trade-off between resolution and gene coverage. Combining scRNA-seq with different spatially-resolved technologies can thus provide a more complete map of tissues with enhanced cellular resolution and gene coverage. Here, we propose DOT, a novel multi-objective optimization framework for transferring cellular features across these data modalities. DOT is flexible and can be used to infer categorical (cell type or cell state) or continuous features (gene expression) in different types of spatial omics. Our optimization model combines practical aspects related to tissue composition, technical effects, and integration of prior knowledge, thereby providing flexibility to combine scRNA-seq and both low- and high-resolution spatial data. Our fast implementation based on the Frank-Wolfe algorithm achieves state-of-the-art or improved performance in localizing cell features in high- and low-resolution spatial data and estimating the expression of unmeasured genes in low-coverage spatial data across different tissues. DOT is freely available and can be deployed efficiently without large computational resources; typical cases-studies can be run on a laptop, facilitating its use.

Yuechen Yang, Junlin Guo, Yanfan Zhu et al.

High-throughput "pathomic" analysis of Whole Slide Images (WSIs) offers new opportunities to study tissue characteristics and for biomarker discovery. However, the clinical relevance of the tissue characteristics at the micro- and macro-environment level is limited by the lack of tools that facilitate the measurement of the spatial interaction of individual structure characteristics and their association with clinical parameters. To address these challenges, we introduce HistoWAS (Histology-Wide Association Study), a computational framework designed to link tissue spatial organization to clinical outcomes. Specifically, HistoWAS implements (1) a feature space that augments conventional metrics with 30 topological and spatial features, adapted from Geographic Information Systems (GIS) point pattern analysis, to quantify tissue micro-architecture; and (2) an association study engine, inspired by Phenome-Wide Association Studies (PheWAS), that performs mass univariate regression for each feature with statistical correction. As a proof of concept, we applied HistoWAS to analyze a total of 102 features (72 conventional object-level features and our 30 spatial features) using 385 PAS-stained WSIs from 206 participants in the Kidney Precision Medicine Project (KPMP). The code and data have been released to https://github.com/hrlblab/histoWAS.

Santanu Subhash Rathod, Francesco Ceccarelli, Sean B. Holden et al.

Inferring trajectories from longitudinal spatially-resolved omics data is fundamental to understanding the dynamics of structural and functional tissue changes in development, regeneration and repair, disease progression, and response to treatment. We propose ContextFlow, a novel context-aware flow matching framework that incorporates prior knowledge to guide the inference of structural tissue dynamics from spatially resolved omics data. Specifically, ContextFlow integrates local tissue organization and ligand-receptor communication patterns into a transition plausibility matrix that regularizes the optimal transport objective. By embedding these contextual constraints, ContextFlow generates trajectories that are not only statistically consistent but also biologically meaningful, making it a generalizable framework for modeling spatiotemporal dynamics from longitudinal, spatially resolved omics data. Evaluated on three datasets, ContextFlow consistently outperforms state-of-the-art flow matching methods across multiple quantitative and qualitative metrics of inference accuracy and biological coherence. Our code is available at: \href{https://github.com/santanurathod/ContextFlow}{ContextFlow}

Žiga Lukšič, Jovan Tanevski, Sašo Džeroski et al.

The central task in modeling complex dynamical systems is parameter estimation. This task involves numerous evaluations of a computationally expensive objective function. Surrogate-based optimization introduces a computationally efficient predictive model that approximates the value of the objective function. The standard approach involves learning a surrogate from training examples that correspond to past evaluations of the objective function. Current surrogate-based optimization methods use static, predefined substitution strategies that decide when to use the surrogate and when the true objective. We introduce a meta-model framework where the substitution strategy is dynamically adapted to the solution space of the given optimization problem. The meta model encapsulates the objective function, the surrogate model and the model of the substitution strategy, as well as components for learning them. The framework can be seamlessly coupled with an arbitrary optimization algorithm without any modification: it replaces the objective function and autonomously decides how to evaluate a given candidate solution. We test the utility of the framework on three tasks of estimating parameters of real-world models of dynamical systems. The results show that the meta model significantly improves the efficiency of optimization, reducing the total number of evaluations of the objective function up to an average of 77%.