Diffusion models exhibit excellent sample quality, but existing guidance methods often require additional model training or are limited to specific tasks. We revisit guidance in diffusion models from the perspective of variational inference and control, introducing \emph{Diffusion Trajectory Matching (DTM)} that enables guiding pretrained diffusion trajectories to satisfy a terminal cost. DTM unifies a broad class of guidance methods and enables novel instantiations. We introduce a new method within this framework that achieves state-of-the-art results on several linear, non-linear, and blind inverse problems without requiring additional model training or specificity to pixel or latent space diffusion models. Our code will be available at https://github.com/czi-ai/oc-guidance.

Event sequences appear widely in domains such as medicine, finance, and remote sensing, yet modeling them is challenging due to their heterogeneity: sequences often contain multiple event types with diverse structures—for example, electronic health records that mix discrete events like medical procedures with continuous lab measurements. Existing approaches either tokenize all entries, violating natural inductive biases, or ignore parts of the data to enforce a consistent structure. In this work, we propose a simple yet powerful Marked Temporal Point Process (MTPP) framework for modeling event sequences with flexible structure, using a single unified model. Our approach employs a single autoregressive transformer with discrete and continuous prediction heads, capable of modeling variable-length, mixed-type event sequences. The continuous head leverages an expressive normalizing flow to model continuous event attributes, avoiding the numerical integration required for inter-event times in most competing methods. Empirically, our model excels on both discrete-only and mixed-type sequences, improving prediction quality and enabling interpretable uncertainty quantification. We make our code public at https://github.com/czi-ai/FlexTPP.

Vision Transformer (ViT) has emerged as a powerful architecture in the realm of modern computer vision. However, its application in certain imaging fields, such as microscopy and satellite imaging, presents unique challenges. In these domains, images often contain multiple channels, each carrying semantically distinct and independent information. Furthermore, the model must demonstrate robustness to sparsity in input channels, as they may not be densely available during training or testing. In this paper, we propose a modification to the ViT architecture that enhances reasoning across the input channels and introduce Hierarchical Channel Sampling (HCS) as an additional regularization technique to ensure robustness when only partial channels are presented during test time. Our proposed model, ChannelViT, constructs patch tokens independently from each input channel and utilizes a learnable channel embedding that is added to the patch tokens, similar to positional embeddings. We evaluate the performance of ChannelViT on ImageNet, JUMP-CP (microscopy cell imaging), and So2Sat (satellite imaging). Our results show that ChannelViT outperforms ViT on classification tasks and generalizes well, even when a subset of input channels is used during testing. Across our experiments, HCS proves to be a powerful regularizer, independent of the architecture employed, suggesting itself as a straightforward technique for robust ViT training. Lastly, we find that ChannelViT generalizes effectively even when there is limited access to all channels during training, highlighting its potential for multi-channel imaging under real-world conditions with sparse sensors. Our code is available at https://github.com/insitro/ChannelViT.

In the current landscape of deep learning research, there is a predominant emphasis on achieving high predictive accuracy in supervised tasks involving large image and language datasets. However, a broader perspective reveals a multitude of overlooked metrics, tasks, and data types, such as uncertainty, active and continual learning, and scientific data, that demand attention. Bayesian deep learning (BDL) constitutes a promising avenue, offering advantages across these diverse settings. This paper posits that BDL can elevate the capabilities of deep learning. It revisits the strengths of BDL, acknowledges existing challenges, and highlights some exciting research avenues aimed at addressing these obstacles. Looking ahead, the discussion focuses on possible ways to combine large-scale foundation models with BDL to unlock their full potential.

Generative models of observations under interventions have been a vibrant topic of interest across machine learning and the sciences in recent years. For example, in drug discovery, there is a need to model the effects of diverse interventions on cells in order to characterize unknown biological mechanisms of action. We propose the Sparse Additive Mechanism Shift Variational Autoencoder, SAMS-VAE, to combine compositionality, disentanglement, and interpretability for perturbation models. SAMS-VAE models the latent state of a perturbed sample as the sum of a local latent variable capturing sample-specific variation and sparse global variables of latent intervention effects. Crucially, SAMS-VAE sparsifies these global latent variables for individual perturbations to identify disentangled, perturbation-specific latent subspaces that are flexibly composable. We evaluate SAMS-VAE both quantitatively and qualitatively on a range of tasks using two popular single cell sequencing datasets. In order to measure perturbation-specific model-properties, we also introduce a framework for evaluation of perturbation models based on average treatment effects with links to posterior predictive checks. SAMS-VAE outperforms comparable models in terms of generalization across in-distribution and out-of-distribution tasks, including a combinatorial reasoning task under resource paucity, and yields interpretable latent structures which correlate strongly to known biological mechanisms. Our results suggest SAMS-VAE is an interesting addition to the modeling toolkit for machine learning-driven scientific discovery.

Recent advances in coreset methods have shown that a selection of representative datapoints can replace massive volumes of data for Bayesian inference, preserving the relevant statistical information and significantly accelerating subsequent downstream tasks. Existing variational coreset constructions rely on either selecting subsets of the observed datapoints, or jointly performing approximate inference and optimizing pseudodata in the observed space akin to inducing points methods in Gaussian Processes. So far, both approaches are limited by complexities in evaluating their objectives for general purpose models, and require generating samples from a typically intractable posterior over the coreset throughout inference and testing. In this work, we present a black-box variational inference framework for coresets that overcomes these constraints and enables principled application of variational coresets to intractable models, such as Bayesian neural networks. We apply our techniques to supervised learning problems, and compare them with existing approaches in the literature for data summarization and inference.

Through sequential construction of posteriors on observing data online, Bayes’ theorem provides a natural framework for continual learning. We develop Variational Auto-Regressive Gaussian Processes (VAR-GPs), a principled posterior updating mechanism to solve sequential tasks in continual learning. By relying on sparse inducing point approximations for scalable posteriors, we propose a novel auto-regressive variational distribution which reveals two fruitful connections to existing results in Bayesian inference, expectation propagation and orthogonal inducing points. Mean predictive entropy estimates show VAR-GPs prevent catastrophic forgetting, which is empirically supported by strong performance on modern continual learning benchmarks against competitive baselines. A thorough ablation study demonstrates the efficacy of our modeling choices.

There is broad interest in creating RL agents that can solve many (related) tasks and adapt to new tasks and environments after initial training. Model-based RL leverages learned surrogate models that describe dynamics and rewards of individual tasks, such that planning in a good surrogate can lead to good control of the true system. Rather than solving each task individually from scratch, hierarchical models can exploit the fact that tasks are often related by (unobserved) causal factors of variation in order to achieve efficient generalization, as in learning how the mass of an item affects the force required to lift it can generalize to previously unobserved masses. We propose Generalized Hidden Parameter MDPs (GHP-MDPs) that describe a family of MDPs where both dynamics and reward can change as a function of hidden parameters that vary across tasks. The GHP-MDP augments model-based RL with latent variables that capture these hidden parameters, facilitating transfer across tasks. We also explore a variant of the model that incorporates explicit latent structure mirroring the causal factors of variation across tasks (for instance: agent properties, environmental factors, and goals). We experimentally demonstrate state-of-the-art performance and sample-efficiency on a new challenging MuJoCo task using reward and dynamics latent spaces, while beating a previous state-of-the-art baseline with > 10× less data. Using test-time inference of the latent variables, our approach generalizes in a single episode to novel combinations of dynamics and reward, and to novel rewards.

Probabilistic neural networks are typically modeled with independent weight priors, which do not capture weight correlations in the prior and do not provide a parsimonious interface to express properties in function space. A desirable class of priors would represent weights compactly, capture correlations between weights, facilitate calibrated reasoning about uncertainty, and allow inclusion of prior knowledge about the function space such as periodicity or dependence on contexts such as inputs. To this end, this paper introduces two innovations: (i) a Gaussian process-based hierarchical model for network weights based on unit embeddings that can flexibly encode correlated weight structures, and (ii) input-dependent versions of these weight priors that can provide convenient ways to regularize the function space through the use of kernels defined on contextual inputs. We show these models provide desirable test-time uncertainty estimates on out-of-distribution data, demonstrate cases of modeling inductive biases for neural networks with kernels which help both interpolation and extrapolation from training data, and demonstrate competitive predictive performance on an active learning benchmark.

We exploit the link between the transport equation and derivatives of expectations to construct efficient pathwise gradient estimators for multivariate distributions. We focus on two main threads. First, we use null solutions of the transport equation to construct adaptive control variates that can be used to construct gradient estimators with reduced variance. Second, we consider the case of multivariate mixture distributions. In particular we show how to compute pathwise derivatives for mixtures of multivariate Normal distributions with arbitrary means and diagonal covariances. We demonstrate in a variety of experiments in the context of variational inference that our gradient estimators can outperform other methods, especially in high dimensions.

Pyro is a probabilistic programming language built on Python as a platform for developing advanced probabilistic models in AI research. To scale to large data sets and high-dimensional models, Pyro uses stochastic variational inference algorithms and probability distributions built on top of PyTorch, a modern GPU-accelerated deep learning framework. To accommodate complex or model-specific algorithmic behavior, Pyro leverages Poutine, a library of composable building blocks for modifying the behavior of probabilistic programs.

What makes images similar? To measure the similarity between images, they are typically embedded in a feature-vector space, in which their distance preserve the relative dissimilarity. However, when learning such similarity embeddings the simplifying assumption is commonly made that images are only compared to one unique measure of similarity. A main reason for this is that contradicting notions of similarities cannot be captured in a single space. To address this shortcoming, we propose Conditional Similarity Networks (CSNs) that learn embeddings differentiated into semantically distinct subspaces that capture the different notions of similarities. CSNs jointly learn a disentangled embedding where features for different similarities are encoded in separate dimensions as well as masks that select and reweight relevant dimensions to induce a subspace that encodes a specific similarity notion. We show that our approach learns interpretable image representations with visually relevant semantic subspaces. Further, when evaluating on triplet questions from multiple similarity notions our model even outperforms the accuracy obtained by training individual specialized networks for each notion separately.

MOTIVATION: Deep sequencing based ribosome footprint profiling can provide novel insights into the regulatory mechanisms of protein translation. However, the observed ribosome profile is fundamentally confounded by transcriptional activity. In order to decipher principles of translation regulation, tools that can reliably detect changes in translation efficiency in case-control studies are needed. RESULTS: We present a statistical framework and an analysis tool, RiboDiff, to detect genes with changes in translation efficiency across experimental treatments. RiboDiff uses generalized linear models to estimate the over-dispersion of RNA-Seq and ribosome profiling measurements separately, and performs a statistical test for differential translation efficiency using both mRNA abundance and ribosome occupancy. AVAILABILITY AND IMPLEMENTATION: RiboDiff webpage http://bioweb.me/ribodiff Source code including scripts for preprocessing the FASTQ data are available at http://github.com/ratschlab/ribodiff CONTACTS: [email protected] or [email protected] information: Supplementary data are available at Bioinformatics online.

Neural language models are a powerful tool to embed words into semantic vector spaces. However, learning such models generally relies on the availability of abundant and diverse training examples. In highly specialised domains this requirement may not be met due to difficulties in obtaining a large corpus, or the limited range of expression in average use. Such domains may encode prior knowledge about entities in a knowledge base or ontology. We propose a generative model which integrates evidence from diverse data sources, enabling the sharing of semantic information. We achieve this by generalising the concept of co-occurrence from distributional semantics to include other relationships between entities or words, which we model as affine transformations on the embedding space. We demonstrate the effectiveness of this approach by outperforming recent models on a link prediction task and demonstrating its ability to profit from partially or fully unobserved data training labels. We further demonstrate the usefulness of learning from different data sources with overlapping vocabularies.

MOTIVATION: Accurate large-scale phenotyping has recently gained considerable importance in biology. For example, in genome-wide association studies technological advances have rendered genotyping cheap, leaving phenotype acquisition as the major bottleneck. Automatic image analysis is one major strategy to phenotype individuals in large numbers. Current approaches for visual phenotyping focus predominantly on summarizing statistics and geometric measures, such as height and width of an individual, or color histograms and patterns. However, more subtle, but biologically informative phenotypes, such as the local deformation of the shape of an individual with respect to the population mean cannot be automatically extracted and quantified by current techniques. RESULTS: We propose a probabilistic machine learning model that allows for the extraction of deformation phenotypes from biological images, making them available as quantitative traits for downstream analysis. Our approach jointly models a collection of images using a learned common template that is mapped onto each image through a deformable smooth transformation. In a case study, we analyze the shape deformations of 388 guppy fish (Poecilia reticulata). We find that the flexible shape phenotypes our model extracts are complementary to basic geometric measures. Moreover, these quantitative traits assort the observations into distinct groups and can be mapped to polymorphic genetic loci of the sample set. AVAILABILITY: Code is available under: http://bioweb.me/GEBI CONTACT: [email protected]; [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.