Auguste Genovesio

Nicolas Bourriez, Ihab Bendidi, Ethan Cohen et al.

Unlike color photography images, which are consistently encoded into RGB channels, biological images encompass various modalities, where the type of microscopy and the meaning of each channel varies with each experiment. Importantly, the number of channels can range from one to a dozen and their correlation is often comparatively much lower than RGB, as each of them brings specific information content. This aspect is largely overlooked by methods designed out of the bioimage field, and current solutions mostly focus on intra-channel spatial attention, often ignoring the relationship between channels, yet crucial in most biological applications. Importantly, the variable channel type and count prevent the projection of several experiments to a unified representation for large scale pre-training. In this study, we propose ChAda-ViT, a novel Channel Adaptive Vision Transformer architecture employing an Inter-Channel Attention mechanism on images with an arbitrary number, order and type of channels. We also introduce IDRCell100k, a bioimage dataset with a rich set of 79 experiments covering 7 microscope modalities, with a multitude of channel types, and counts varying from 1 to 10 per experiment. Our architecture, trained in a self-supervised manner, outperforms existing approaches in several biologically relevant downstream tasks. Additionally, it can be used to bridge the gap for the first time between assays with different microscopes, channel numbers or types by embedding various image and experimental modalities into a unified biological image representation. The latter should facilitate interdisciplinary studies and pave the way for better adoption of deep learning in biological image-based analyses. Code and Data available at https://github.com/nicoboou/chadavit.

Ihab Bendidi, Adrien Bardes, Ethan Cohen et al.

Self-supervised representation learning in computer vision relies heavily on hand-crafted image transformations to learn meaningful and invariant features. However few extensive explorations of the impact of transformation design have been conducted in the literature. In particular, the dependence of downstream performances to transformation design has been established, but not studied in depth. In this work, we explore this relationship, its impact on a domain other than natural images, and show that designing the transformations can be viewed as a form of supervision. First, we demonstrate that not only do transformations have an effect on downstream performance and relevance of clustering, but also that each category in a supervised dataset can be impacted in a different way. Following this, we explore the impact of transformation design on microscopy images, a domain where the difference between classes is more subtle and fuzzy than in natural images. In this case, we observe a greater impact on downstream tasks performances. Finally, we demonstrate that transformation design can be leveraged as a form of supervision, as careful selection of these by a domain expert can lead to a drastic increase in performance on a given downstream task.

Anis Bourou, Auguste Genovesio

Unpaired image-to-image translation methods aim at learning a mapping of images from a source domain to a target domain. Recently, these methods proved to be very useful in biological applications to display subtle phenotypic cell variations otherwise invisible to the human eye. However, current models require a large number of images to be trained, while mostmicroscopy experiments remain limited in the number of images they can produce. In this work, we present an improved CycleGAN architecture that employs self-supervised discriminators to alleviate the need for numerous images. We demonstrate quantitatively and qualitatively that the proposed approach outperforms the CycleGAN baseline, including when it is combined with differentiable augmentations. We also provide results obtained with small biological datasets on obvious and non-obvious cell phenotype variations, demonstrating a straightforward application of this method.

Umar Masud, Ethan Cohen, Ihab Bendidi et al.

Progress in automated microscopy and quantitative image analysis has promoted high-content screening (HCS) as an efficient drug discovery and research tool. While HCS offers to quantify complex cellular phenotypes from images at high throughput, this process can be obstructed by image aberrations such as out-of-focus image blur, fluorophore saturation, debris, a high level of noise, unexpected auto-fluorescence or empty images. While this issue has received moderate attention in the literature, overlooking these artefacts can seriously hamper downstream image processing tasks and hinder detection of subtle phenotypes. It is therefore of primary concern, and a prerequisite, to use quality control in HCS. In this work, we evaluate deep learning options that do not require extensive image annotations to provide a straightforward and easy to use semi-supervised learning solution to this issue. Concretely, we compared the efficacy of recent self-supervised and transfer learning approaches to provide a base encoder to a high throughput artefact image detector. The results of this study suggest that transfer learning methods should be preferred for this task as they not only performed best here but present the advantage of not requiring sensitive hyperparameter settings nor extensive additional training.

Alexandre Myara, Nicolas Bourriez, Thomas Boyer et al.

Disentangled representation learning aims to map independent factors of variation to independent representation components. On one hand, purely unsupervised approaches have proven successful on fully disentangled synthetic data, but fail to recover semantic factors from real data without strong inductive biases. On the other hand, supervised approaches are unstable and hard to scale to large attribute sets because they rely on adversarial objectives or auxiliary classifiers. We introduce \textsc{XFactors}, a weakly-supervised VAE framework that disentangles and provides explicit control over a chosen set of factors. Building on the Disentangled Information Bottleneck perspective, we decompose the representation into a residual subspace $\mathcal{S}$ and factor-specific subspaces $\mathcal{T}_1,\ldots,\mathcal{T}_K$ and a residual subspace $\mathcal{S}$. Each target factor is encoded in its assigned $\mathcal{T}_i$ through contrastive supervision: an InfoNCE loss pulls together latents sharing the same factor value and pushes apart mismatched pairs. In parallel, KL regularization imposes a Gaussian structure on both $\mathcal{S}$ and the aggregated factor subspaces, organizing the geometry without additional supervision for non-targeted factors and avoiding adversarial training and classifiers. Across multiple datasets, with constant hyperparameters, \textsc{XFactors} achieves state-of-the-art disentanglement scores and yields consistent qualitative factor alignment in the corresponding subspaces, enabling controlled factor swapping via latent replacement. We further demonstrate that our method scales correctly with increasing latent capacity and evaluate it on the real-world dataset CelebA. Our code is available at \href{https://github.com/ICML26-anon/XFactors}{github.com/ICML26-anon/XFactors}.

Marzieh Gheisari, Auguste Genovesio

This paper addresses the problem of super-resolution: constructing a highly resolved (HR) image from a low resolved (LR) one. Recent unsupervised approaches search the latent space of a StyleGAN pre-trained on HR images, for the image that best downscales to the input LR image. However, they tend to produce out-of-domain images and fail to accurately reconstruct HR images that are far from the original domain. Our contribution is twofold. Firstly, we introduce a new regularizer to constrain the search in the latent space, ensuring that the inverted code lies in the original image manifold. Secondly, we further enhanced the reconstruction through expanding the image prior around the optimal latent code. Our results show that the proposed approach recovers realistic high-quality images for large magnification factors. Furthermore, for low magnification factors, it can still reconstruct details that the generator could not have produced otherwise. Altogether, our approach achieves a good trade-off between fidelity and realism for the super-resolution task.

Sandeep Manandhar, Auguste Genovesio

In this paper, we propose a style-based conditional video generative model. We introduce a novel temporal generator based on a set of learned sinusoidal bases. Our method learns dynamic representations of various actions that are independent of image content and can be transferred between different actors. Beyond the significant enhancement of video quality compared to prevalent methods, we demonstrate that the disentangled dynamic and content permit their independent manipulation, as well as temporal GAN-inversion to retrieve and transfer a video motion from one content or identity to another without further preprocessing such as landmark points.

Anis Bourou, Valérie Mezger, Auguste Genovesio

In recent years, Generative Adversarial Networks (GANs) have seen significant advancements, leading to their widespread adoption across various fields. The original GAN architecture enables the generation of images without any specific control over the content, making it an unconditional generation process. However, many practical applications require precise control over the generated output, which has led to the development of conditional GANs (cGANs) that incorporate explicit conditioning to guide the generation process. cGANs extend the original framework by incorporating additional information (conditions), enabling the generation of samples that adhere to that specific criteria. Various conditioning methods have been proposed, each differing in how they integrate the conditioning information into both the generator and the discriminator networks. In this work, we review the conditioning methods proposed for GANs, exploring the characteristics of each method and highlighting their unique mechanisms and theoretical foundations. Furthermore, we conduct a comparative analysis of these methods, evaluating their performance on various image datasets. Through these analyses, we aim to provide insights into the strengths and limitations of various conditioning techniques, guiding future research and application in generative modeling.

Ivan Svatko, Maxime Sanchez, Ihab Bendidi et al.

Representation learning has driven major advances in natural image analysis by enabling models to acquire high-level semantic features. In microscopy imaging, however, it remains unclear what current representation learning methods actually learn. In this work, we conduct a systematic study of representation learning for the two most widely used and broadly available microscopy data types, representing critical scales in biology: cell culture and tissue imaging. To this end, we introduce a set of simple yet revealing baselines on curated benchmarks, including untrained models and simple structural representations of cellular tissue. Our results show that, surprisingly, state-of-the-art methods perform comparably to these baselines. We further show that, in contrast to natural images, existing models fail to consistently acquire high-level, biologically meaningful features. Moreover, we demonstrate that commonly used benchmark metrics are insufficient to assess representation quality and often mask this limitation. In addition, we investigate how detailed comparisons with these benchmarks provide ways to interpret the strengths and weaknesses of models for further improvements. Together, our results suggest that progress in microscopy image representation learning requires not only stronger models, but also more diagnostic benchmarks that measure what is actually learned.

Anis Bourou, Thomas Boyer, Kévin Daupin et al.

For the past few years, deep generative models have increasingly been used in biological research for a variety of tasks. Recently, they have proven to be valuable for uncovering subtle cell phenotypic differences that are not directly discernible to the human eye. However, current methods employed to achieve this goal mainly rely on Generative Adversarial Networks (GANs). While effective, GANs encompass issues such as training instability and mode collapse, and they do not accurately map images back to the model's latent space, which is necessary to synthesize, manipulate, and thus interpret outputs based on real images. In this work, we introduce PhenDiff: a multi-class conditional method leveraging Diffusion Models (DMs) designed to identify shifts in cellular phenotypes by translating a real image from one condition to another. We qualitatively and quantitatively validate this method on cases where the phenotypic changes are visible or invisible, such as in low concentrations of drug treatments. Overall, PhenDiff represents a valuable tool for identifying cellular variations in real microscopy images. We anticipate that it could facilitate the understanding of diseases and advance drug discovery through the identification of novel biomarkers.

Marzieh Gheisari, Auguste Genovesio

Unsupervised disentanglement of static appearance and dynamic motion in video remains a fundamental challenge, often hindered by information leakage and blurry reconstructions in existing VAE- and GAN-based approaches. We introduce DiViD, the first end-to-end video diffusion framework for explicit static-dynamic factorization. DiViD's sequence encoder extracts a global static token from the first frame and per-frame dynamic tokens, explicitly removing static content from the motion code. Its conditional DDPM decoder incorporates three key inductive biases: a shared-noise schedule for temporal consistency, a time-varying KL-based bottleneck that tightens at early timesteps (compressing static information) and relaxes later (enriching dynamics), and cross-attention that routes the global static token to all frames while keeping dynamic tokens frame-specific. An orthogonality regularizer further prevents residual static-dynamic leakage. We evaluate DiViD on real-world benchmarks using swap-based accuracy and cross-leakage metrics. DiViD outperforms state-of-the-art sequential disentanglement methods: it achieves the highest swap-based joint accuracy, preserves static fidelity while improving dynamic transfer, and reduces average cross-leakage.

Thomas Gravier, Thomas Boyer, Auguste Genovesio

Many natural dynamic processes -- such as in vivo cellular differentiation or disease progression -- can only be observed through the lens of static sample snapshots. While challenging, reconstructing their temporal evolution to decipher underlying dynamic properties is of major interest to scientific research. Existing approaches enable data transport along a temporal axis but are poorly scalable in high dimension and require restrictive assumptions to be met. To address these issues, we propose \textit{\textbf{Multi-Marginal temporal Schrödinger Bridge Matching}} (\textbf{MMtSBM}) \textit{for video generation from unpaired data}, extending the theoretical guarantees and empirical efficiency of Diffusion Schrödinger Bridge Matching (arXiv:archive/2303.16852) by deriving the Iterative Markovian Fitting algorithm to multiple marginals in a novel factorized fashion. Experiments show that MMtSBM retains theoretical properties on toy examples, achieves state-of-the-art performance on real world datasets such as transcriptomic trajectory inference in 100 dimensions, and for the first time recovers couplings and dynamics in very high dimensional image settings. Our work establishes multi-marginal Schrödinger bridges as a practical and principled approach for recovering hidden dynamics from static data.

Qiuyu Chen, Xin Jin, Yue Song et al.

This paper reviews the 1st International Workshop on Disentangled Representation Learning for Controllable Generation (DRL4Real), held in conjunction with ICCV 2025. The workshop aimed to bridge the gap between the theoretical promise of Disentangled Representation Learning (DRL) and its application in realistic scenarios, moving beyond synthetic benchmarks. DRL4Real focused on evaluating DRL methods in practical applications such as controllable generation, exploring advancements in model robustness, interpretability, and generalization. The workshop accepted 9 papers covering a broad range of topics, including the integration of novel inductive biases (e.g., language), the application of diffusion models to DRL, 3D-aware disentanglement, and the expansion of DRL into specialized domains like autonomous driving and EEG analysis. This summary details the workshop's objectives, the themes of the accepted papers, and provides an overview of the methodologies proposed by the authors.

Ihab Bendidi, Yassir El Mesbahi, Alisandra K. Denton et al.

Understanding cellular responses to stimuli is crucial for biological discovery and drug development. Transcriptomics provides interpretable, gene-level insights, while microscopy imaging offers rich predictive features but is harder to interpret. Weakly paired datasets, where samples share biological states, enable multimodal learning but are scarce, limiting their utility for training and multimodal inference. We propose a framework to enhance transcriptomics by distilling knowledge from microscopy images. Using weakly paired data, our method aligns and binds modalities, enriching gene expression representations with morphological information. To address data scarcity, we introduce (1) Semi-Clipped, an adaptation of CLIP for cross-modal distillation using pretrained foundation models, achieving state-of-the-art results, and (2) PEA (Perturbation Embedding Augmentation), a novel augmentation technique that enhances transcriptomics data while preserving inherent biological information. These strategies improve the predictive power and retain the interpretability of transcriptomics, enabling rich unimodal representations for complex biological tasks.

Anis Bourou, Biel Castaño Segade, Thomas Boye et al.

Identifying subtle phenotypic variations in cellular images is critical for advancing biological research and accelerating drug discovery. These variations are often masked by the inherent cellular heterogeneity, making it challenging to distinguish differences between experimental conditions. Recent advancements in deep generative models have demonstrated significant potential for revealing these nuanced phenotypes through image translation, opening new frontiers in cellular and molecular biology as well as the identification of novel biomarkers. Among these generative models, diffusion models stand out for their ability to produce high-quality, realistic images. However, training diffusion models typically requires large datasets and substantial computational resources, both of which can be limited in biological research. In this work, we propose a novel approach that leverages pre-trained latent diffusion models to uncover subtle phenotypic changes. We validate our approach qualitatively and quantitatively on several small datasets of microscopy images. Our findings reveal that our approach enables effective detection of phenotypic variations, capturing both visually apparent and imperceptible differences. Ultimately, our results highlight the promising potential of this approach for phenotype detection, especially in contexts constrained by limited data and computational capacity.

Anis Bourou, Saranga Kingkor Mahanta, Thomas Boyer et al.

In recent years, deep learning models have been extensively applied to biological data across various modalities. Discriminative deep learning models have excelled at classifying images into categories (e.g., healthy versus diseased, treated versus untreated). However, these models are often perceived as black boxes due to their complexity and lack of interpretability, limiting their application in real-world biological contexts. In biological research, explainability is essential: understanding classifier decisions and identifying subtle differences between conditions are critical for elucidating the effects of treatments, disease progression, and biological processes. To address this challenge, we propose DiffEx, a method for generating visually interpretable attributes to explain classifiers and identify microscopic cellular variations between different conditions. We demonstrate the effectiveness of DiffEx in explaining classifiers trained on natural and biological images. Furthermore, we use DiffEx to uncover phenotypic differences within microscopy datasets. By offering insights into cellular variations through classifier explanations, DiffEx has the potential to advance the understanding of diseases and aid drug discovery by identifying novel biomarkers.