arXiv subjects

Olivier Michielin

Publications and source records attributed to Olivier Michielin.

7 recordsLinked to original sources

arXiv2026

spora: A Unified Multimodal Dataset and Platform for Spatial Proteomics

Spatial proteomics (SP) captures the molecular composition and spatial organization of tissues at single-cell resolution, opening a direct view of the cellular ecosystems that drive disease. Protein panels, acquisition platforms, and tissue contexts differ from one cohort to the next, and a coherent picture of tissue biology can only emerge from models trained to bridge this heterogeneity. Foundation models offer the natural path forward, but their training depends on large, harmonized corpora that span platforms, panels, and cohorts. No public resource currently approaches that scale; available data sit in small, narrowly scoped releases with incompatible formats and conventions. We present $\texttt{spora}$, a large-scale multimodal SP dataset of 13,546 standardized multiplex images from 5,477 patients across 35 cohorts and five major SP technologies. Curated with biomedical experts, $\texttt{spora}$ provides model training-ready formats together with cell and tissue segmentations, structured clinical metadata, and, where available, paired H&E enabling the training of virtual staining models. It is complemented by $\texttt{spora [io]}$, a unified interface for tiling, sampling, and standardization across all cohorts and modalities, and $\texttt{spora [bench]}$, a benchmark suite spanning cell phenotyping, diagnostic and therapeutic prediction as well as virtual staining tasks across twelve cohorts that places current SP foundation models on common ground against task specific baselines.

cs.CV↗

arXiv2026

Ontology-Based Post-Coordinated Expression Assembly: from Clinical Narrative to Queryable Knowledge Graphs

Clinical oncology documentation records decisive information in free text, where it remains readable but not retrievable at scale, leaving cohort identification dependent on incomplete diagnostic codes or manual review. The current standard, coding individual terms, captures what a document mentions, not what it asserts: meaning lies in how those terms relate to one another. We present a method for deriving queryable knowledge graphs from clinical narratives, conforming to the Extended Grammar of SNOMED CT across multiple ontologies. The method specifies how entities should be annotated and related. It defines five relation classes, each bound to a construction rule that assembles the entities and relations into post-coordinated expressions. A deterministic implementation, UNIGRAPHE, applies those rules to construct knowledge graphs from annotated text. Applied to expert-annotated real-world oncology documentation, UNIGRAPHE reconstructed 5,299 annotations into 2,196 post-coordinated expressions and shows that relation structure is the missing piece to make clinical narrative formally queryable.

cs.CL↗

arXiv2025

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↗

arXiv2025

MTBBench: A Multimodal Sequential Clinical Decision-Making Benchmark in Oncology

Multimodal Large Language Models (LLMs) hold promise for biomedical reasoning, but current benchmarks fail to capture the complexity of real-world clinical workflows. Existing evaluations primarily assess unimodal, decontextualized question-answering, overlooking multi-agent decision-making environments such as Molecular Tumor Boards (MTBs). MTBs bring together diverse experts in oncology, where diagnostic and prognostic tasks require integrating heterogeneous data and evolving insights over time. Current benchmarks lack this longitudinal and multimodal complexity. We introduce MTBBench, an agentic benchmark simulating MTB-style decision-making through clinically challenging, multimodal, and longitudinal oncology questions. Ground truth annotations are validated by clinicians via a co-developed app, ensuring clinical relevance. We benchmark multiple open and closed-source LLMs and show that, even at scale, they lack reliability -- frequently hallucinating, struggling with reasoning from time-resolved data, and failing to reconcile conflicting evidence or different modalities. To address these limitations, MTBBench goes beyond benchmarking by providing an agentic framework with foundation model-based tools that enhance multi-modal and longitudinal reasoning, leading to task-level performance gains of up to 9.0% and 11.2%, respectively. Overall, MTBBench offers a challenging and realistic testbed for advancing multimodal LLM reasoning, reliability, and tool-use with a focus on MTB environments in precision oncology.

cs.LG↗

arXiv2025

FRACCO: A gold-standard annotated corpus of oncological entities with ICD-O-3.1 normalisation

Developing natural language processing tools for clinical text requires annotated datasets, yet French oncology resources remain scarce. We present FRACCO (FRench Annotated Corpus for Clinical Oncology) an expert-annotated corpus of 1301 synthetic French clinical cases, initially translated from the Spanish CANTEMIST corpus as part of the FRASIMED initiative. Each document is annotated with terms related to morphology, topography, and histologic differentiation, using the International Classification of Diseases for Oncology (ICD-O) as reference. An additional annotation layer captures composite expression-level normalisations that combine multiple ICD-O elements into unified clinical concepts. Annotation quality was ensured through expert review: 1301 texts were manually annotated for entity spans by two domain experts. A total of 71127 ICD-O normalisations were produced through a combination of automated matching and manual validation by a team of five annotators. The final dataset representing 399 unique morphology codes (from 2549 different expressions), 272 topography codes (from 3143 different expressions), and 2043 unique composite expressions (from 11144 different expressions). This dataset provides a reference standard for named entity recognition and concept normalisation in French oncology texts.

cs.CL↗

arXiv2024

HoverFast: an accurate, high-throughput, clinically deployable nuclear segmentation tool for brightfield digital pathology images

In computational digital pathology, accurate nuclear segmentation of Hematoxylin and Eosin (H&E) stained whole slide images (WSIs) is a critical step for many analyses and tissue characterizations. One popular deep learning-based nuclear segmentation approach, HoverNet, offers remarkably accurate results but lacks the high-throughput performance needed for clinical deployment in resource-constrained settings. Our approach, HoverFast, aims to provide fast and accurate nuclear segmentation in H&E images using knowledge distillation from HoverNet. By redesigning the tool with software engineering best practices, HoverFast introduces advanced parallel processing capabilities, efficient data handling, and optimized postprocessing. These improvements facilitate scalable high-throughput performance, making HoverFast more suitable for real-time analysis and application in resource-limited environments. Using a consumer grade Nvidia A5000 GPU, HoverFast showed a 21x speed improvement as compared to HoverNet; reducing mean analysis time for 40x WSIs from ~2 hours to 6 minutes while retaining a concordant mean Dice score of 0.91 against the original HoverNet output. Peak memory usage was also reduced 71% from 44.4GB, to 12.8GB, without requiring SSD-based caching. To ease adoption in research and clinical contexts, HoverFast aligns with best-practices in terms of (a) installation, and (b) containerization, while (c) providing outputs compatible with existing popular open-source image viewing tools such as QuPath. HoverFast has been made open-source and is available at andrewjanowczyk.com/open-source-tools/hoverfast.

q-bio.QM↗

arXiv2005

Functional Dynamics of PDZ Binding Domains: A Normal Mode Analysis

PDZ (Post-synaptic density-95/discs large/zonula occludens-1) domains are relatively small (80 to 120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino-acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible of communication between distant regions of the protein, in agreement with recent Nuclear Magnetic Resonance (NMR) experiments. Thus PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbonding events.

q-bio.BM↗