The quality of self-supervised pre-trained embeddings on out-of-distribution (OOD) data is poor without fine-tuning. A straightforward and simple approach to improving the generalization of pre-trained representation to OOD data is the use of deep ensembles. However, obtaining an effective ensemble in the embedding space with only unlabeled data remains an unsolved problem. We first perform a theoretical analysis that reveals the relationship between individual hyperspherical embedding spaces in an ensemble. We then design a principled method to align these embedding spaces in an unsupervised manner. Experimental results on the MNIST dataset show that our embedding-space ensemble method improves pre-trained embedding quality on in-distribution and OOD data compared to single encoders.

In this paper, we consider the problem of causal order discovery within the framework of monotonic Structural Causal Models (SCMs), which have gained attention for their potential to enable causal inference and causal discovery from observational data. While existing approaches either assume prior knowledge about the causal order or use complex optimization techniques to impose sparsity in the Jacobian of Triangular Monotonic Increasing maps, our work introduces a novel sequential procedure that directly identifies the causal order by iteratively detecting the root variable. This method eliminates the need for sparsity assumptions and the associated optimization challenges, enabling the identification of a unique SCM without the need for multiple independence tests to break the Markov equivalence class. We demonstrate the effectiveness of our approach in sequentially finding the root variable, comparing it to methods that maximize Jacobian sparsity.

Generative models in drug discovery have recently gained attention as efficient alternatives to brute-force virtual screening. However, most existing models do not account for synthesizability, limiting their practical use in real-world scenarios. In this paper, we propose RxnFlow, which sequentially assembles molecules using predefined molecular building blocks and chemical reaction templates to constrain the synthetic chemical pathway. We then train on this sequential generating process with the objective of generative flow networks (GFlowNets) to generate both highly rewarded and diverse molecules. To mitigate the large action space of synthetic pathways in GFlowNets, we implement a novel action space subsampling method. This enables RxnFlow to learn generative flows over extensive action spaces comprising combinations of 1.2 million building blocks and 71 reaction templates without significant computational overhead. Additionally, RxnFlow can employ modified or expanded action spaces for generation without retraining, allowing for the introduction of additional objectives or the incorporation of newly discovered building blocks. We experimentally demonstrate that RxnFlow outperforms existing reaction-based and fragment-based models in pocket-specific optimization across various target pockets. Furthermore, RxnFlow achieves state-of-the-art performance on CrossDocked2020 for pocket-conditional generation, with an average Vina score of -8.85kcal/mol and 34.8% synthesizability.

We seek to automate the generation of drug-like compounds conditioned to specific protein pocket targets. Most current methods approximate the protein-molecule distribution of a finite dataset and, therefore struggle to generate molecules with significant binding improvement over the training dataset. We instead frame the pocket-conditioned molecular generation task as an RL problem and develop TacoGFN, a target conditional Generative Flow Network model. Our method is explicitly encouraged to generate molecules with desired properties as opposed to fitting on a pre-existing data distribution. To this end, we develop transformer-based docking score prediction to speed up docking score computation and propose TacoGFN to explore molecule space efficiently. Furthermore, we incorporate several rounds of active learning where generated samples are queried using a docking oracle to improve the docking score prediction. This approach allows us to accurately explore as much of the molecule landscape as we can afford computationally. Empirically, molecules generated using TacoGFN and its variants significantly outperform all baseline methods across every property (Docking score, QED, SA, Lipinski), while being orders of magnitude faster.

Individual treatment effect (ITE) estimation requires adjusting for the covariate shift between populations with different treatments, and deep representation learning has shown great promise in learning a balanced representation of covariates. However the existing methods mostly consider the scenario of binary treatments. In this paper, we consider the more practical and challenging scenario in which the treatment is a continuous variable (e.g. dosage of a medication), and we address the two main challenges of this setup. We propose the adversarial counterfactual regression network (ACFR) that adversarially minimizes the representation imbalance in terms of KL divergence, and also maintains the impact of the treatment value on the outcome prediction by leveraging an attention mechanism. Theoretically we demonstrate that ACFR objective function is grounded in an upper bound on counterfactual outcome prediction error. Our experimental evaluation on semi-synthetic datasets demonstrates the empirical superiority of ACFR over a range of state-of-the-art methods.

Molecular Representation Learning is essential to solving many drug discovery and computational chemistry problems. It is a challenging problem due to the complex structure of molecules and the vast chemical space. Graph representations of molecules are more expressive than traditional representations, such as molecular fingerprints. Therefore, they can improve the performance of machine learning models. We propose SeMole, a method that augments the Junction Tree Variational Autoencoders, a state-of-the-art generative model for molecular graphs, with semi-supervised learning. SeMole aims to improve the accuracy of molecular property prediction when having limited labeled data by exploiting unlabeled data. We enforce that the model generates molecular graphs conditioned on target properties by incorporating the property into the latent representation. We propose an additional pre-training phase to improve the training process for our semi-supervised generative model. We perform an experimental evaluation on the ZINC dataset using three different molecular properties and demonstrate the benefits of semi-supervision.

This work proposes the M3E2, a multi-task learning neural network model to estimate the effect of multiple treatments. In contrast to existing methods, M3E2 is robust to multiple treatment effects applied simultaneously to the same unit, continuous and binary treatments, and many covariates. We compared M3E2 with three baselines in three synthetic benchmark datasets: two with multiple treatments and one with one treatment. Our analysis showed that our method has superior performance, making more assertive estimations of the true treatment effects. The code is available at github.com/raquelaoki/M3E2.

The goal of few-shot classification is to learn a model that can classify novel classes using only a few training examples. Despite the promising results shown by existing meta-learning algorithms in solving the few-shot classification problem, there still remains an important challenge: how to generalize to unseen domains while meta-learning on multiple seen domains? In this paper, we propose an optimization-based meta-learning method, called Combining Domain-Specific Meta-Learners (CosML), that addresses the cross-domain few-shot classification problem. CosML first trains a set of meta-learners, one for each training domain, to learn prior knowledge (i.e., meta-parameters) specific to each domain. The domain-specific meta-learners are then combined in the \emph{parameter space}, by taking a weighted average of their meta-parameters, which is used as the initialization parameters of a task network that is quickly adapted to novel few-shot classification tasks in an unseen domain. Our experiments show that CosML outperforms a range of state-of-the-art methods and achieves strong cross-domain generalization ability.

The goal of domain generalization is to learn from multiple source domains to generalize to unseen target domains under distribution discrepancy. Current state-of-the-art methods in this area are fully supervised, but for many real-world problems it is hardly possible to obtain enough labeled samples. In this paper, we propose the first method of domain generalization to leverage unlabeled samples, combining of meta learning's episodic training and semi-supervised learning, called DGSML. DGSML employs an entropy-based pseudo-labeling approach to assign labels to unlabeled samples and then utilizes a novel discrepancy loss to ensure that class centroids before and after labeling unlabeled samples are close to each other. To learn a domain-invariant representation, it also utilizes a novel alignment loss to ensure that the distance between pairs of class centroids, computed after adding the unlabeled samples, is preserved across different domains. DGSML is trained by a meta learning approach to mimic the distribution shift between the input source domains and unseen target domains. Experimental results on benchmark datasets indicate that DGSML outperforms state-of-the-art domain generalization and semi-supervised learning methods.

We study the problem of applying spectral clustering to cluster multi-scale data, which is data whose clusters are of various sizes and densities. Traditional spectral clustering techniques discover clusters by processing a similarity matrix that reflects the proximity of objects. For multi-scale data, distance-based similarity is not effective because objects of a sparse cluster could be far apart while those of a dense cluster have to be sufficiently close. Following [16], we solve the problem of spectral clustering on multi-scale data by integrating the concept of objects' "reachability similarity" with a given distance-based similarity to derive an objects' coefficient matrix. We propose the algorithm CAST that applies trace Lasso to regularize the coefficient matrix. We prove that the resulting coefficient matrix has the "grouping effect" and that it exhibits "sparsity". We show that these two characteristics imply very effective spectral clustering. We evaluate CAST and 10 other clustering methods on a wide range of datasets w.r.t. various measures. Experimental results show that CAST provides excellent performance and is highly robust across test cases of multi-scale data.