Paul-Henry Cournède

Leo Fillioux, Joseph Boyd, Maria Vakalopoulou et al.

Multiple instance learning is an ideal mode of analysis for histopathology data, where vast whole slide images are typically annotated with a single global label. In such cases, a whole slide image is modelled as a collection of tissue patches to be aggregated and classified. Common models for performing this classification include recurrent neural networks and transformers. Although powerful compression algorithms, such as deep pre-trained neural networks, are used to reduce the dimensionality of each patch, the sequences arising from whole slide images remain excessively long, routinely containing tens of thousands of patches. Structured state space models are an emerging alternative for sequence modelling, specifically designed for the efficient modelling of long sequences. These models invoke an optimal projection of an input sequence into memory units that compress the entire sequence. In this paper, we propose the use of state space models as a multiple instance learner to a variety of problems in digital pathology. Across experiments in metastasis detection, cancer subtyping, mutation classification, and multitask learning, we demonstrate the competitiveness of this new class of models with existing state of the art approaches. Our code is available at https://github.com/MICS-Lab/s4_digital_pathology.

Quentin Blampey, Nadège Bercovici, Charles-Antoine Dutertre et al.

Cytometry enables precise single-cell phenotyping within heterogeneous populations. These cell types are traditionally annotated via manual gating, but this method suffers from a lack of reproducibility and sensitivity to batch-effect. Also, the most recent cytometers - spectral flow or mass cytometers - create rich and high-dimensional data whose analysis via manual gating becomes challenging and time-consuming. To tackle these limitations, we introduce Scyan (https://github.com/MICS-Lab/scyan), a Single-cell Cytometry Annotation Network that automatically annotates cell types using only prior expert knowledge about the cytometry panel. We demonstrate that Scyan significantly outperforms the related state-of-the-art models on multiple public datasets while being faster and interpretable. In addition, Scyan overcomes several complementary tasks such as batch-effect removal, debarcoding, and population discovery. Overall, this model accelerates and eases cell population characterisation, quantification, and discovery in cytometry.

Hakim Benkirane, Yoann Pradat, Stefan Michiels et al.

Recent advances in high-throughput sequencing technologies have enabled the extraction of multiple features that depict patient samples at diverse and complementary molecular levels. The generation of such data has led to new challenges in computational biology regarding the integration of high-dimensional and heterogeneous datasets that capture the interrelationships between multiple genes and their functions. Thanks to their versatility and ability to learn synthetic latent representations of complex data, deep learning methods offer promising perspectives for integrating multi-omics data. These methods have led to the conception of many original architectures that are primarily based on autoencoder models. However, due to the difficulty of the task, the integration strategy is fundamental to take full advantage of the sources' particularities without losing the global trends. This paper presents a novel strategy to build a customizable autoencoder model that adapts to the dataset used in the case of high-dimensional multi-source integration. We will assess the impact of integration strategies on the latent representation and combine the best strategies to propose a new method, CustOmics (https://github.com/HakimBenkirane/CustOmics). We focus here on the integration of data from multiple omics sources and demonstrate the performance of the proposed method on test cases for several tasks such as classification and survival analysis.

Leo Fillioux, Enzo Ferrante, Paul-Henry Cournède et al.

Large foundation models have emerged in the last years and are pushing performance boundaries for a variety of tasks. Training or even finetuning such models demands vast datasets and computational resources, which are often scarce and costly. Adaptation methods provide a computationally efficient solution to address these limitations by allowing such models to be finetuned on small amounts of data and computing power. This is achieved by appending new trainable modules to frozen backbones with only a fraction of the trainable parameters and fitting only these modules on novel tasks. Recently, the VeRA adapter was shown to excel in parameter-efficient adaptations by utilizing a pair of frozen random low-rank matrices shared across all layers. In this paper, we propose PVeRA, a probabilistic version of the VeRA adapter, which modifies the low-rank matrices of VeRA in a probabilistic manner. This modification naturally allows handling inherent ambiguities in the input and allows for different sampling configurations during training and testing. A comprehensive evaluation was performed on the VTAB-1k benchmark and seven adapters, with PVeRA outperforming VeRA and other adapters. Our code for training models with PVeRA and benchmarking all adapters is available https://github.com/leofillioux/pvera.

Leo Fillioux, Emilie Gontran, Jérôme Cartry et al.

Over the last ten years, Patient-Derived Organoids (PDOs) emerged as the most reliable technology to generate ex-vivo tumor avatars. PDOs retain the main characteristics of their original tumor, making them a system of choice for pre-clinical and clinical studies. In particular, PDOs are attracting interest in the field of Functional Precision Medicine (FPM), which is based upon an ex-vivo drug test in which living tumor cells (such as PDOs) from a specific patient are exposed to a panel of anti-cancer drugs. Currently, the Adenosine Triphosphate (ATP) based cell viability assay is the gold standard test to assess the sensitivity of PDOs to drugs. The readout is measured at the end of the assay from a global PDO population and therefore does not capture single PDO responses and does not provide time resolution of drug effect. To this end, in this study, we explore for the first time the use of powerful large foundation models for the automatic processing of PDO data. In particular, we propose a novel imaging-based high-throughput screening method to assess real-time drug efficacy from a time-lapse microscopy video of PDOs. The recently proposed SAM algorithm for segmentation and DINOv2 model are adapted in a comprehensive pipeline for processing PDO microscopy frames. Moreover, an attention mechanism is proposed for fusing temporal and spatial features in a multiple instance learning setting to predict ATP. We report better results than other non-time-resolved methods, indicating that the temporality of data is an important factor for the prediction of ATP. Extensive ablations shed light on optimizing the experimental setting and automating the prediction both in real-time and for forecasting.

Leo Fillioux, Omprakash Chakraborty, Ismail Ben Ayed et al.

With the increasing adoption of vision-language models (VLMs) in critical decision-making systems such as healthcare or autonomous driving, the calibration of their uncertainty estimates becomes paramount. Yet, this dimension has been largely underexplored in the VLM test-time prompt-tuning (TPT) literature, which has predominantly focused on improving their discriminative performance. Recent state-of-the-art advocates for enforcing full orthogonality over pairs of text prompt embeddings to enhance separability, and therefore calibration. Nevertheless, as we theoretically show in this work, the inherent gradients from fully orthogonal constraints will strongly push semantically related classes away, ultimately making the model overconfident. Based on our findings, we propose Semantic Orthogonal Calibration (SoC), a Huber-based regularizer that enforces smooth prototype separation while preserving semantic proximity, thereby improving calibration compared to prior orthogonality-based approaches. Across a comprehensive empirical validation, we demonstrate that SoC consistently improves calibration performance, while also maintaining competitive discriminative capabilities.

Mouad El Bouchattaoui, Myriam Tami, Benoit Lepetit et al.

Accurately estimating treatment effects over time is crucial in fields such as precision medicine, epidemiology, economics, and marketing. Many current methods for estimating treatment effects over time assume that all confounders are observed or attempt to infer unobserved ones. In contrast, our approach focuses on unobserved adjustment variables, which specifically have a causal effect on the outcome sequence. Under the assumption of unconfoundedness, we address estimating Conditional Average Treatment Effects (CATEs) while accounting for unobserved heterogeneity in response to treatment due to these unobserved adjustment variables. Our proposed Causal Dynamic Variational Autoencoder (CDVAE) is grounded in theoretical guarantees concerning the validity of latent adjustment variables and generalization bounds on CATE estimation error. Extensive evaluations on synthetic and real-world datasets show that CDVAE outperforms existing baselines. Moreover, we demonstrate that state-of-the-art models significantly improve their CATE estimates when augmented with the latent substitutes learned by CDVAE, approaching oracle-level performance without direct access to the true adjustment variables.

Leo Fillioux, Julio Silva-Rodríguez, Ismail Ben Ayed et al.

Recent advances in self-supervision and contrastive learning have brought the performance of foundation models to unprecedented levels in a variety of tasks. Fueled by this progress, these models are becoming the prevailing approach for a wide array of real-world vision problems, including risk-sensitive and high-stakes applications. However, ensuring safe deployment in these scenarios requires a more comprehensive understanding of their uncertainty modeling capabilities, which has been barely explored. In this work, we delve into the behaviour of vision and vision-language foundation models under Conformal Prediction (CP), a statistical framework that provides theoretical guarantees of marginal coverage of the true class. Across extensive experiments including popular vision classification benchmarks, well-known foundation vision models, and three CP methods, our findings reveal that foundation models are well-suited for conformalization procedures, particularly those integrating Vision Transformers. We also show that calibrating the confidence predictions of these models, a popular strategy to improve their uncertainty quantification, actually leads to efficiency degradation of the conformal set on adaptive CP methods. Furthermore, few-shot adaptation of Vision-Language Models (VLMs) to downstream tasks, whose popularity is surging, enhances conformal scores compared to zero-shot predictions. Last, our empirical study exposes APS as particularly promising in the context of vision foundation models, as it does not violate the marginal coverage guarantees across multiple challenging, yet realistic scenarios.

Mouad El Bouchattaoui, Myriam Tami, Benoit Lepetit et al.

Estimating treatment effects over time holds significance in various domains, including precision medicine, epidemiology, economy, and marketing. This paper introduces a unique approach to counterfactual regression over time, emphasizing long-term predictions. Distinguishing itself from existing models like Causal Transformer, our approach highlights the efficacy of employing RNNs for long-term forecasting, complemented by Contrastive Predictive Coding (CPC) and Information Maximization (InfoMax). Emphasizing efficiency, we avoid the need for computationally expensive transformers. Leveraging CPC, our method captures long-term dependencies in the presence of time-varying confounders. Notably, recent models have disregarded the importance of invertible representation, compromising identification assumptions. To remedy this, we employ the InfoMax principle, maximizing a lower bound of mutual information between sequence data and its representation. Our method achieves state-of-the-art counterfactual estimation results using both synthetic and real-world data, marking the pioneering incorporation of Contrastive Predictive Encoding in causal inference.

Martin Charachon, Paul-Henry Cournède, Céline Hudelot et al.

Providing a human-understandable explanation of classifiers' decisions has become imperative to generate trust in their use for day-to-day tasks. Although many works have addressed this problem by generating visual explanation maps, they often provide noisy and inaccurate results forcing the use of heuristic regularization unrelated to the classifier in question. In this paper, we propose a new general perspective of the visual explanation problem overcoming these limitations. We show that visual explanation can be produced as the difference between two generated images obtained via two specific conditional generative models. Both generative models are trained using the classifier to explain and a database to enforce the following properties: (i) All images generated by the first generator are classified similarly to the input image, whereas the second generator's outputs are classified oppositely. (ii) Generated images belong to the distribution of real images. (iii) The distances between the input image and the corresponding generated images are minimal so that the difference between the generated elements only reveals relevant information for the studied classifier. Using symmetrical and cyclic constraints, we present two different approximations and implementations of the general formulation. Experimentally, we demonstrate significant improvements w.r.t the state-of-the-art on three different public data sets. In particular, the localization of regions influencing the classifier is consistent with human annotations.

Martin Charachon, Céline Hudelot, Paul-Henry Cournède et al.

Explaining decisions of black-box classifiers is paramount in sensitive domains such as medical imaging since clinicians confidence is necessary for adoption. Various explanation approaches have been proposed, among which perturbation based approaches are very promising. Within this class of methods, we leverage a learning framework to produce our visual explanations method. From a given classifier, we train two generators to produce from an input image the so called similar and adversarial images. The similar image shall be classified as the input image whereas the adversarial shall not. Visual explanation is built as the difference between these two generated images. Using metrics from the literature, our method outperforms state-of-the-art approaches. The proposed approach is model-agnostic and has a low computation burden at prediction time. Thus, it is adapted for real-time systems. Finally, we show that random geometric augmentations applied to the original image play a regularization role that improves several previously proposed explanation methods. We validate our approach on a large chest X-ray database.