SUMMARY: We present PyDESeq2, a python implementation of the DESeq2 workflow for differential expression analysis on bulk RNA-seq data. This re-implementation yields similar, but not identical, results: it achieves higher model likelihood, allows speed improvements on large datasets, as shown in experiments on TCGA data, and can be more easily interfaced with modern python-based data science tools. AVAILABILITY AND IMPLEMENTATION: PyDESeq2 is released as an open-source software under the MIT license. The source code is available on GitHub at https://github.com/owkin/PyDESeq2 and documented at https://pydeseq2.readthedocs.io. PyDESeq2 is part of the scverse ecosystem.

Gradient Langevin dynamics (GLD) and stochastic GLD (SGLD) have attracted considerable attention lately, as a way to provide convergence guarantees in a non-convex setting. However, the known rates grow exponentially with the dimension of the space under the dissipative condition. In this work, we provide a convergence analysis of GLD and SGLD when the optimization space is an infinite-dimensional Hilbert space. More precisely, we derive non-asymptotic, dimension-free convergence rates for GLD/SGLD when performing regularized non-convex optimization in a reproducing kernel Hilbert space. Amongst others, the convergence analysis relies on the properties of a stochastic differential equation, its discrete time Galerkin approximation and the geometric ergodicity of the associated Markov chains.

The Yeo-Johnson (YJ) transformation is a standard parametrized per-feature unidimensional transformation often used to Gaussianize features in machine learning. In this paper, we investigate the problem of applying the YJ transformation in a cross-silo Federated Learning setting under privacy constraints. For the first time, we prove that the YJ negative log-likelihood is in fact convex, which allows us to optimize it with exponential search. We numerically show that the resulting algorithm is more stable than the state-of-the-art approach based on the Brent minimization method. Building on this simple algorithm and Secure Multiparty Computation routines, we propose SECUREFEDYJ, a federated algorithm that performs a pooled-equivalent YJ transformation without leaking more information than the final fitted parameters do. Quantitative experiments on real data demonstrate that, in addition to being secure, our approach reliably normalizes features across silos as well as if data were pooled, making it a viable approach for safe federated feature Gaussianization.

Federated Learning (FL) is a novel approach enabling several clients holding sensitive data to collaboratively train machine learning models, without centralizing data. The cross-silo FL setting corresponds to the case of few ($2$--$50$) reliable clients, each holding medium to large datasets, and is typically found in applications such as healthcare, finance, or industry. While previous works have proposed representative datasets for cross-device FL, few realistic healthcare cross-silo FL datasets exist, thereby slowing algorithmic research in this critical application. In this work, we propose a novel cross-silo dataset suite focused on healthcare, FLamby (Federated Learning AMple Benchmark of Your cross-silo strategies), to bridge the gap between theory and practice of cross-silo FL.FLamby encompasses 7 healthcare datasets with natural splits, covering multiple tasks, modalities, and data volumes, each accompanied with baseline training code. As an illustration, we additionally benchmark standard FL algorithms on all datasets.Our flexible and modular suite allows researchers to easily download datasets, reproduce results and re-use the different components for their research. FLamby is available at~\url{www.github.com/owkin/flamby}.

It is well-known that plug-in statistical estimation of optimal transport suffers from the curse of dimensionality. Despite recent efforts to improve the rate of estimation with the smoothness of the problem, the computational complexity of these recently proposed methods still degrade exponentially with the dimension. In this paper, thanks to an infinite-dimensional sum-of-squares representation, we derive a statistical estimator of smooth optimal transport which achieves a precision $\varepsilon$ from $\tilde{O}(\varepsilon^{-2})$ independent and identically distributed samples from the distributions, for a computational cost of $\tilde{O}(\varepsilon^{-4})$ when the smoothness increases, hence yielding dimension-free statistical \emph{and} computational rates, with potentially exponentially dimension-dependent constants.

Missing data is a crucial issue when applying machine learning algorithms to real-world datasets. Starting from the simple assumption that two batches extracted randomly from the same dataset should share the same distribution, we leverage optimal transport distances to quantify that criterion and turn it into a loss function to impute missing data values. We propose practical methods to minimize these losses using end-to-end learning, that can exploit or not parametric assumptions on the underlying distributions of values. We evaluate our methods on datasets from the UCI repository, in MCAR, MAR and MNAR settings. These experiments show that OT-based methods match or out-perform state-of-the-art imputation methods, even for high percentages of missing values.

Although optimal transport (OT) problems admit closed form solutions in a very few notable cases, e.g. in 1D or between Gaussians, these closed forms have proved extremely fecund for practitioners to define tools inspired from the OT geometry. On the other hand, the numerical resolution of OT problems using entropic regularization has given rise to many applications, but because there are no known closed-form solutions for entropic regularized OT problems, these approaches are mostly algorithmic, not informed by elegant closed forms. In this paper, we propose to fill the void at the intersection between these two schools of thought in OT by proving that the entropy-regularized optimal transport problem between two Gaussian measures admits a closed form. Contrary to the unregularized case, for which the explicit form is given by the Wasserstein-Bures distance, the closed form we obtain is differentiable everywhere, even for Gaussians with degenerate covariance matrices. We obtain this closed form solution by solving the fixed-point equation behind Sinkhorn's algorithm, the default method for computing entropic regularized OT. Remarkably, this approach extends to the generalized unbalanced case --- where Gaussian measures are scaled by positive constants. This extension leads to a closed form expression for unbalanced Gaussians as well, and highlights the mass transportation / destruction trade-off seen in unbalanced optimal transport. Moreover, in both settings, we show that the optimal transportation plans are (scaled) Gaussians and provide analytical formulas of their parameters. These formulas constitute the first non-trivial closed forms for entropy-regularized optimal transport, thus providing a ground truth for the analysis of entropic OT and Sinkhorn's algorithm.

Computing optimal transport (OT) between measures in high dimensions is doomed by the curse of dimensionality. A popular approach to avoid this curse is to project input measures on lower-dimensional subspaces (1D lines in the case of sliced Wasserstein distances), solve the OT problem between these reduced measures, and settle for the Wasserstein distance between these reductions, rather than that between the original measures. This approach is however difficult to extend to the case in which one wants to compute an OT map (a Monge map) between the original measures. Since computations are carried out on lower-dimensional projections, classical map estimation techniques can only produce maps operating in these reduced dimensions. We propose in this work two methods to extrapolate, from an transport map that is optimal on a subspace, one that is nearly optimal in the entire space. We prove that the best optimal transport plan that takes such "subspace detours" is a generalization of the Knothe-Rosenblatt transport. We show that these plans can be explicitly formulated when comparing Gaussian measures (between which the Wasserstein distance is commonly referred to as the Bures or Fréchet distance). We provide an algorithm to select optimal subspaces given pairs of Gaussian measures, and study scenarios in which that mediating subspace can be selected using prior information. We consider applications to semantic mediation between elliptic word embeddings and domain adaptation with Gaussian mixture models.

Embedding complex objects as vectors in low dimensional spaces is a longstanding problem in machine learning. We propose in this work an extension of that approach, which consists in embedding objects as elliptical probability distributions, namely distributions whose densities have elliptical level sets. We endow these measures with the 2-Wasserstein metric, with two important benefits: (i) For such measures, the squared 2-Wasserstein metric has a closed form, equal to a weighted sum of the squared Euclidean distance between means and the squared Bures metric between covariance matrices. The latter is a Riemannian metric between positive semi-definite matrices, which turns out to be Euclidean on a suitable factor representation of such matrices, which is valid on the entire geodesic between these matrices. (ii) The 2-Wasserstein distance boils down to the usual Euclidean metric when comparing Diracs, and therefore provides a natural framework to extend point embeddings. We show that for these reasons Wasserstein elliptical embeddings are more intuitive and yield tools that are better behaved numerically than the alternative choice of Gaussian embeddings with the Kullback-Leibler divergence. In particular, and unlike previous work based on the KL geometry, we learn elliptical distributions that are not necessarily diagonal. We demonstrate the advantages of elliptical embeddings by using them for visualization, to compute embeddings of words, and to reflect entailment or hypernymy.

Optimal transport is a powerful framework for computing distances between probability distributions. We unify the two main approaches to optimal transport, namely Monge-Kantorovitch and Sinkhorn-Cuturi, into what we define as Tsallis regularized optimal transport (TROT). TROT interpolates a rich family of distortions from Wasserstein to Kullback-Leibler, encompassing as well Pearson, Neyman and Hellinger divergences, to name a few. We show that metric properties known for Sinkhorn-Cuturi generalize to TROT, and provide efficient algorithms for finding the optimal transportation plan with formal convergence proofs. We also present the first application of optimal transport to the problem of ecological inference, that is, the reconstruction of joint distributions from their marginals, a problem of large interest in the social sciences. TROT provides a convenient framework for ecological inference by allowing to compute the joint distribution -— that is, the optimal transportation plan itself — when side information is available, which is e.g. typically what census represents in political science. Experiments on data from the 2012 US presidential elections display the potential of TROT in delivering a faithful reconstruction of the joint distribution of ethnic groups and voter preferences.

We study the classification with respect to the class of curved Mahalanobis metrics that extend the celebrated flat Mahalanobis distances to constant curvature spaces. We prove that these curved Mahalanobis k-NN classifiers define piecewise linear decision boundaries, and report the performance of learning those metrics within the framework of the Large Margin Nearest Neighbor (LMNN). Finally, we show experimentally that a mixture of curved Mahalanobis metrics define a composite metric distance that improves the classification performance.