Nous utilisons des témoins pour analyser le trafic et l’utilisation de notre site web, afin de personnaliser votre expérience. Vous pouvez désactiver ces technologies à tout moment, mais cela peut restreindre certaines fonctionnalités du site. Consultez notre Politique de protection de la vie privée pour en savoir plus.
Paramètre des cookies
Vous pouvez activer et désactiver les types de cookies que vous souhaitez accepter. Cependant certains choix que vous ferez pourraient affecter les services proposés sur nos sites (ex : suggestions, annonces personnalisées, etc.).
Cookies essentiels
Ces cookies sont nécessaires au fonctionnement du site et ne peuvent être désactivés. (Toujours actif)
Cookies analyse
Acceptez-vous l'utilisation de cookies pour mesurer l'audience de nos sites ?
Multimedia Player
Acceptez-vous l'utilisation de cookies pour afficher et vous permettre de regarder les contenus vidéo hébergés par nos partenaires (YouTube, etc.) ?
Publications
Novel cell states arise in embryonic cells devoid of key reprogramming factors
The capacity for embryonic cells to differentiate relies on a large-scale reprogramming of the oocyte and sperm nucleus into a transient tot… (voir plus)ipotent state. In zebrafish, this reprogramming step is achieved by the pioneer factors Nanog, Pou5f3, and Sox19b (NPS). Yet, it remains unclear whether cells lacking this reprogramming step are directed towards wild type states or towards novel developmental canals in the Waddington landscape of embryonic development. Here we investigate the developmental fate of embryonic cells mutant for NPS by analyzing their single-cell gene expression profiles. We find that cells lacking the first developmental reprogramming steps can acquire distinct cell states. These states are manifested by gene expression modules that result from a failure of nuclear reprogramming, the persistence of the maternal program, and the activation of somatic compensatory programs. As a result, most mutant cells follow new developmental canals and acquire new mixed cell states in development. In contrast, a group of mutant cells acquire primordial germ cell-like states, suggesting that NPS-dependent reprogramming is dispensable for these cell states. Together, these results demonstrate that developmental reprogramming after fertilization is required to differentiate most canonical developmental programs, and loss of the transient totipotent state canalizes embryonic cells into new developmental states in vivo.
In this work, we propose Salient Sparse Federated Learning (SSFL), a streamlined approach for sparse federated learning with efficient commu… (voir plus)nication. SSFL identifies a sparse subnetwork prior to training, leveraging parameter saliency scores computed separately on local client data in non-IID scenarios, and then aggregated, to determine a global mask. Only the sparse model weights are communicated each round between the clients and the server. We validate SSFL's effectiveness using standard non-IID benchmarks, noting marked improvements in the sparsity--accuracy trade-offs. Finally, we deploy our method in a real-world federated learning framework and report improvement in communication time.
Identifying functionally important cell states and structure within a heterogeneous tumor remains a significant biological and computational… (voir plus) challenge. Moreover, current clustering or trajectory-based computational models are ill-equipped to address the notion that cancer cells reside along a phenotypic continuum. To address this, we present Archetypal Analysis network (AAnet), a neural network that learns key archetypal cell states within a phenotypic continuum of cell states in single-cell data. Applied to single-cell RNA sequencing data from pre-clinical models and a cohort of 34 clinical breast cancers, AAnet identifies archetypes that resolve distinct biological cell states and processes, including cell proliferation, hypoxia, metabolism and immune interactions. Notably, archetypes identified in primary tumors are recapitulated in matched liver, lung and lymph node metastases, demonstrating that a significant component of intratumoral heterogeneity is driven by cell intrinsic properties. Using spatial transcriptomics as orthogonal validation, AAnet-derived archetypes show discrete spatial organization within tumors, supporting their distinct archetypal biology. We further reveal that ligand:receptor cross-talk between cancer and adjacent stromal cells contributes to intra-archetypal biological mimicry. Finally, we use AAnet archetype identifiers to validate GLUT3 as a critical mediator of a hypoxic cell archetype harboring a cancer stem cell population, which we validate in human triple-negative breast cancer specimens. AAnet is a powerful tool to reveal functional cell states within complex samples from multimodal single-cell data.
We investigate the challenge of multi-agent deep reinforcement learning in partially competitive environments, where traditional methods str… (voir plus)uggle to foster reciprocity-based cooperation. LOLA and POLA agents learn reciprocity-based cooperative policies by differentiation through a few look-ahead optimization steps of their opponent. However, there is a key limitation in these techniques. Because they consider a few optimization steps, a learning opponent that takes many steps to optimize its return may exploit them. In response, we introduce a novel approach, Best Response Shaping (BRS), which differentiates through an opponent approximating the best response, termed the "detective." To condition the detective on the agent's policy for complex games we propose a state-aware differentiable conditioning mechanism, facilitated by a question answering (QA) method that extracts a representation of the agent based on its behaviour on specific environment states. To empirically validate our method, we showcase its enhanced performance against a Monte Carlo Tree Search (MCTS) opponent, which serves as an approximation to the best response in the Coin Game. This work expands the applicability of multi-agent RL in partially competitive environments and provides a new pathway towards achieving improved social welfare in general sum games.
We introduce GRouNdGAN, a gene regulatory network (GRN)-guided causal implicit generative model for simulating single-cell RNA-seq data, in-… (voir plus)silico perturbation experiments, and benchmarking GRN inference methods. Through the imposition of a user-defined GRN in its architecture, GRouNdGAN simulates steady-state and transient-state single-cell datasets where genes are causally expressed under the control of their regulating transcription factors (TFs). Training on three experimental datasets, we show that our model captures non-linear TF-gene dependences and preserves gene identities, cell trajectories, pseudo-time ordering, and technical and biological noise, with no user manipulation and only implicit parameterization. Despite imposing rigid causality constraints, it outperforms state-of-the-art simulators in generating realistic cells. GRouNdGAN learns meaningful causal regulatory dynamics, allowing sampling from both observational and interventional distributions. This enables it to synthesize cells under conditions that do not occur in the dataset at inference time, allowing to perform in-silico TF knockout experiments. Our results show that in-silico knockout of cell type-specific TFs significantly reduces cells of that type being generated. Interactions imposed through the GRN are emphasized in the simulated datasets, resulting in GRN inference algorithms assigning them much higher scores than interactions not imposed but of equal importance in the experimental training dataset. Benchmarking various GRN inference algorithms reveals that GRouNdGAN effectively bridges the existing gap between simulated and biological data benchmarks of GRN inference algorithms, providing gold standard ground truth GRNs and realistic cells corresponding to the biological system of interest. Our results show that GRouNdGAN is a stable, realistic, and effective simulator with various applications in single-cell RNA-seq analysis.
Both entropy-minimizing and entropy-maximizing (curiosity) objectives for unsupervised reinforcement learning (RL) have been shown to be eff… (voir plus)ective in different environments, depending on the environment's level of natural entropy. However, neither method alone results in an agent that will consistently learn intelligent behavior across environments. In an effort to find a single entropy-based method that will encourage emergent behaviors in any environment, we propose an agent that can adapt its objective online, depending on the entropy conditions by framing the choice as a multi-armed bandit problem. We devise a novel intrinsic feedback signal for the bandit, which captures the agent's ability to control the entropy in its environment. We demonstrate that such agents can learn to control entropy and exhibit emergent behaviors in both high- and low-entropy regimes and can learn skillful behaviors in benchmark tasks. Videos of the trained agents and summarized findings can be found on our project page https://sites.google.com/view/surprise-adaptive-agents
Knowledge distillation is a commonly-used compression method in ML due to the popularity of increasingly large-scale models, but it is uncle… (voir plus)ar if all the information a teacher model contains is distilled into the smaller student model. We aim to formalize the concept of ‘knowledge’ to investigate how knowledge is transferred during distillation, focusing on shared invariant outputs to counterfactual changes of dataset latent variables (we call these latents mechanisms). We define a student model to be a good stand-in model for a teacher if it shares the teacher’s learned mechanisms, and find that Jacobian matching and contrastive representation learning are viable methods by which to train such models. While these methods do not result in perfect transfer of mechanisms, we show they often improve student fidelity or mitigate simplicity bias (as measured by the teacher-to-student KL divergence and accuracy on various out-of-distribution test datasets), especially on datasets with spurious statistical correlations.
2024-05-14
Proceedings of UniReps: the First Workshop on Unifying Representations in Neural Models (publié)
