Matthieu Kirchmeyer

Alexandre Ramé, Matthieu Kirchmeyer, Thibaud Rahier et al.

Standard neural networks struggle to generalize under distribution shifts in computer vision. Fortunately, combining multiple networks can consistently improve out-of-distribution generalization. In particular, weight averaging (WA) strategies were shown to perform best on the competitive DomainBed benchmark; they directly average the weights of multiple networks despite their nonlinearities. In this paper, we propose Diverse Weight Averaging (DiWA), a new WA strategy whose main motivation is to increase the functional diversity across averaged models. To this end, DiWA averages weights obtained from several independent training runs: indeed, models obtained from different runs are more diverse than those collected along a single run thanks to differences in hyperparameters and training procedures. We motivate the need for diversity by a new bias-variance-covariance-locality decomposition of the expected error, exploiting similarities between WA and standard functional ensembling. Moreover, this decomposition highlights that WA succeeds when the variance term dominates, which we show occurs when the marginal distribution changes at test time. Experimentally, DiWA consistently improves the state of the art on DomainBed without inference overhead.

Yuan Yin, Matthieu Kirchmeyer, Jean-Yves Franceschi et al.

Effective data-driven PDE forecasting methods often rely on fixed spatial and / or temporal discretizations. This raises limitations in real-world applications like weather prediction where flexible extrapolation at arbitrary spatiotemporal locations is required. We address this problem by introducing a new data-driven approach, DINo, that models a PDE's flow with continuous-time dynamics of spatially continuous functions. This is achieved by embedding spatial observations independently of their discretization via Implicit Neural Representations in a small latent space temporally driven by a learned ODE. This separate and flexible treatment of time and space makes DINo the first data-driven model to combine the following advantages. It extrapolates at arbitrary spatial and temporal locations; it can learn from sparse irregular grids or manifolds; at test time, it generalizes to new grids or resolutions. DINo outperforms alternative neural PDE forecasters in a variety of challenging generalization scenarios on representative PDE systems.

Nataša Tagasovska, Ji Won Park, Matthieu Kirchmeyer et al.

Machine learning (ML) has demonstrated significant promise in accelerating drug design. Active ML-guided optimization of therapeutic molecules typically relies on a surrogate model predicting the target property of interest. The model predictions are used to determine which designs to evaluate in the lab, and the model is updated on the new measurements to inform the next cycle of decisions. A key challenge is that the experimental feedback from each cycle inspires changes in the candidate proposal or experimental protocol for the next cycle, which lead to distribution shifts. To promote robustness to these shifts, we must account for them explicitly in the model training. We apply domain generalization (DG) methods to classify the stability of interactions between an antibody and antigen across five domains defined by design cycles. Our results suggest that foundational models and ensembling improve predictive performance on out-of-distribution domains. We publicly release our codebase extending the DG benchmark ``DomainBed,'' and the associated dataset of antibody sequences and structures emulating distribution shifts across design cycles.

Matthieu Kirchmeyer, Pedro O. Pinheiro, Emma Willett et al.

Generative models for structure-based drug design are often limited to a specific modality, restricting their broader applicability. To address this challenge, we introduce FuncBind, a framework based on computer vision to generate target-conditioned, all-atom molecules across atomic systems. FuncBind uses neural fields to represent molecules as continuous atomic densities and employs score-based generative models with modern architectures adapted from the computer vision literature. This modality-agnostic representation allows a single unified model to be trained on diverse atomic systems, from small to large molecules, and handle variable atom/residue counts, including non-canonical amino acids. FuncBind achieves competitive in silico performance in generating small molecules, macrocyclic peptides, and antibody complementarity-determining region loops, conditioned on target structures. FuncBind also generated in vitro novel antibody binders via de novo redesign of the complementarity-determining region H3 loop of two chosen co-crystal structures. As a final contribution, we introduce a new dataset and benchmark for structure-conditioned macrocyclic peptide generation. The code is available at https://github.com/prescient-design/funcbind.

Matthieu Kirchmeyer, Pedro O. Pinheiro, Saeed Saremi

We introduce a new representation for 3D molecules based on their continuous atomic density fields. Using this representation, we propose a new model based on walk-jump sampling for unconditional 3D molecule generation in the continuous space using neural fields. Our model, FuncMol, encodes molecular fields into latent codes using a conditional neural field, samples noisy codes from a Gaussian-smoothed distribution with Langevin MCMC (walk), denoises these samples in a single step (jump), and finally decodes them into molecular fields. FuncMol performs all-atom generation of 3D molecules without assumptions on the molecular structure and scales well with the size of molecules, unlike most approaches. Our method achieves competitive results on drug-like molecules and easily scales to macro-cyclic peptides, with at least one order of magnitude faster sampling. The code is available at https://github.com/prescient-design/funcmol.

Matthieu Kirchmeyer, Yuan Yin, Jérémie Donà et al.

Data-driven approaches to modeling physical systems fail to generalize to unseen systems that share the same general dynamics with the learning domain, but correspond to different physical contexts. We propose a new framework for this key problem, context-informed dynamics adaptation (CoDA), which takes into account the distributional shift across systems for fast and efficient adaptation to new dynamics. CoDA leverages multiple environments, each associated to a different dynamic, and learns to condition the dynamics model on contextual parameters, specific to each environment. The conditioning is performed via a hypernetwork, learned jointly with a context vector from observed data. The proposed formulation constrains the search hypothesis space to foster fast adaptation and better generalization across environments. We theoretically motivate our approach and show state-of-the-art generalization results on a set of nonlinear dynamics, representative of a variety of application domains. We also show, on these systems, that new system parameters can be inferred from context vectors with minimal supervision. Code is available at https://github.com/yuan-yin/CoDA .

Matthieu Kirchmeyer, Alain Rakotomamonjy, Emmanuel de Bezenac et al.

We consider the problem of unsupervised domain adaptation (UDA) between a source and a target domain under conditional and label shift a.k.a Generalized Target Shift (GeTarS). Unlike simpler UDA settings, few works have addressed this challenging problem. Recent approaches learn domain-invariant representations, yet they have practical limitations and rely on strong assumptions that may not hold in practice. In this paper, we explore a novel and general approach to align pretrained representations, which circumvents existing drawbacks. Instead of constraining representation invariance, it learns an optimal transport map, implemented as a NN, which maps source representations onto target ones. Our approach is flexible and scalable, it preserves the problem's structure and it has strong theoretical guarantees under mild assumptions. In particular, our solution is unique, matches conditional distributions across domains, recovers target proportions and explicitly controls the target generalization risk. Through an exhaustive comparison on several datasets, we challenge the state-of-the-art in GeTarS.

Matthieu Kirchmeyer, Patrick Gallinari, Alain Rakotomamonjy et al.

We consider unsupervised domain adaptation (UDA) for classification problems in the presence of missing data in the unlabelled target domain. More precisely, motivated by practical applications, we analyze situations where distribution shift exists between domains and where some components are systematically absent on the target domain without available supervision for imputing the missing target components. We propose a generative approach for imputation. Imputation is performed in a domain-invariant latent space and leverages indirect supervision from a complete source domain. We introduce a single model performing joint adaptation, imputation and classification which, under our assumptions, minimizes an upper bound of its target generalization error and performs well under various representative divergence families (H-divergence, Optimal Transport). Moreover, we compare the target error of our Adaptation-imputation framework and the "ideal" target error of a UDA classifier without missing target components. Our model is further improved with self-training, to bring the learned source and target class posterior distributions closer. We perform experiments on three families of datasets of different modalities: a classical digit classification benchmark, the Amazon product reviews dataset both commonly used in UDA and real-world digital advertising datasets. We show the benefits of jointly performing adaptation, classification and imputation on these datasets.

Karan Aggarwal, Matthieu Kirchmeyer, Pranjul Yadav et al.

In recent years, impressive progress has been made in the design of implicit probabilistic models via Generative Adversarial Networks (GAN) and its extension, the Conditional GAN (CGAN). Excellent solutions have been demonstrated mostly in image processing applications which involve large, continuous output spaces. There is almost no application of these powerful tools to problems having small dimensional output spaces. Regression problems involving the inductive learning of a map, $y=f(x,z)$, $z$ denoting noise, $f:\mathbb{R}^n\times \mathbb{R}^k \rightarrow \mathbb{R}^m$, with $m$ small (e.g., $m=1$ or just a few) is one good case in point. The standard approach to solve regression problems is to probabilistically model the output $y$ as the sum of a mean function $m(x)$ and a noise term $z$; it is also usual to take the noise to be a Gaussian. These are done for convenience sake so that the likelihood of observed data is expressible in closed form. In the real world, on the other hand, stochasticity of the output is usually caused by missing or noisy input variables. Such a real world situation is best represented using an implicit model in which an extra noise vector, $z$ is included with $x$ as input. CGAN is naturally suited to design such implicit models. This paper makes the first step in this direction and compares the existing regression methods with CGAN. We notice however, that the existing methods like mixture density networks (MDN) and XGBoost do quite well compared to CGAN in terms of likelihood and mean absolute error, respectively. Both these methods are comparatively easier to train than CGANs. CGANs need more innovation to have a comparable modeling and ease-of-training with respect to the existing regression solvers. In summary, for modeling uncertainty MDNs are better while XGBoost is better for the cases where accurate prediction is more important.