Andrew Jesson

Yashas Annadani, Panagiotis Tigas, Desi R. Ivanova et al. · microsoft-research

We introduce a gradient-based approach for the problem of Bayesian optimal experimental design to learn causal models in a batch setting -- a critical component for causal discovery from finite data where interventions can be costly or risky. Existing methods rely on greedy approximations to construct a batch of experiments while using black-box methods to optimize over a single target-state pair to intervene with. In this work, we completely dispose of the black-box optimization techniques and greedy heuristics and instead propose a conceptually simple end-to-end gradient-based optimization procedure to acquire a set of optimal intervention target-state pairs. Such a procedure enables parameterization of the design space to efficiently optimize over a batch of multi-target-state interventions, a setting which has hitherto not been explored due to its complexity. We demonstrate that our proposed method outperforms baselines and existing acquisition strategies in both single-target and multi-target settings across a number of synthetic datasets.

Panagiotis Tigas, Yashas Annadani, Andrew Jesson et al.

Causal discovery from observational and interventional data is challenging due to limited data and non-identifiability: factors that introduce uncertainty in estimating the underlying structural causal model (SCM). Selecting experiments (interventions) based on the uncertainty arising from both factors can expedite the identification of the SCM. Existing methods in experimental design for causal discovery from limited data either rely on linear assumptions for the SCM or select only the intervention target. This work incorporates recent advances in Bayesian causal discovery into the Bayesian optimal experimental design framework, allowing for active causal discovery of large, nonlinear SCMs while selecting both the interventional target and the value. We demonstrate the performance of the proposed method on synthetic graphs (Erdos-Rènyi, Scale Free) for both linear and nonlinear SCMs as well as on the \emph{in-silico} single-cell gene regulatory network dataset, DREAM.

Shreshth A. Malik, Salem Lahlou, Andrew Jesson et al. · mila

We introduce BatchGFN -- a novel approach for pool-based active learning that uses generative flow networks to sample sets of data points proportional to a batch reward. With an appropriate reward function to quantify the utility of acquiring a batch, such as the joint mutual information between the batch and the model parameters, BatchGFN is able to construct highly informative batches for active learning in a principled way. We show our approach enables sampling near-optimal utility batches at inference time with a single forward pass per point in the batch in toy regression problems. This alleviates the computational complexity of batch-aware algorithms and removes the need for greedy approximations to find maximizers for the batch reward. We also present early results for amortizing training across acquisition steps, which will enable scaling to real-world tasks.

Andrew Jesson, Alyson Douglas, Peter Manshausen et al.

Estimating the effects of continuous-valued interventions from observational data is a critically important task for climate science, healthcare, and economics. Recent work focuses on designing neural network architectures and regularization functions to allow for scalable estimation of average and individual-level dose-response curves from high-dimensional, large-sample data. Such methodologies assume ignorability (observation of all confounding variables) and positivity (observation of all treatment levels for every covariate value describing a set of units), assumptions problematic in the continuous treatment regime. Scalable sensitivity and uncertainty analyses to understand the ignorance induced in causal estimates when these assumptions are relaxed are less studied. Here, we develop a continuous treatment-effect marginal sensitivity model (CMSM) and derive bounds that agree with the observed data and a researcher-defined level of hidden confounding. We introduce a scalable algorithm and uncertainty-aware deep models to derive and estimate these bounds for high-dimensional, large-sample observational data. We work in concert with climate scientists interested in the climatological impacts of human emissions on cloud properties using satellite observations from the past 15 years. This problem is known to be complicated by many unobserved confounders.

Andrew Jesson, Chris Lu, Gunshi Gupta et al.

This paper proposes a step toward approximate Bayesian inference in on-policy actor-critic deep reinforcement learning. It is implemented through three changes to the Asynchronous Advantage Actor-Critic (A3C) algorithm: (1) applying a ReLU function to advantage estimates, (2) spectral normalization of actor-critic weights, and (3) incorporating \emph{dropout as a Bayesian approximation}. We prove under standard assumptions that restricting policy updates to positive advantages optimizes for value by maximizing a lower bound on the value function plus an additive term. We show that the additive term is bounded proportional to the Lipschitz constant of the value function, which offers theoretical grounding for spectral normalization of critic weights. Finally, our application of dropout corresponds to approximate Bayesian inference over both the actor and critic parameters, which enables \textit{adaptive state-aware} exploration around the modes of the actor via Thompson sampling. We demonstrate significant improvements for median and interquartile mean metrics over A3C, PPO, SAC, and TD3 on the MuJoCo continuous control benchmark and improvement over PPO in the challenging ProcGen generalization benchmark.

Miruna Oprescu, Jacob Dorn, Marah Ghoummaid et al.

Estimating heterogeneous treatment effects from observational data is a crucial task across many fields, helping policy and decision-makers take better actions. There has been recent progress on robust and efficient methods for estimating the conditional average treatment effect (CATE) function, but these methods often do not take into account the risk of hidden confounding, which could arbitrarily and unknowingly bias any causal estimate based on observational data. We propose a meta-learner called the B-Learner, which can efficiently learn sharp bounds on the CATE function under limits on the level of hidden confounding. We derive the B-Learner by adapting recent results for sharp and valid bounds of the average treatment effect (Dorn et al., 2021) into the framework given by Kallus & Oprescu (2023) for robust and model-agnostic learning of conditional distributional treatment effects. The B-Learner can use any function estimator such as random forests and deep neural networks, and we prove its estimates are valid, sharp, efficient, and have a quasi-oracle property with respect to the constituent estimators under more general conditions than existing methods. Semi-synthetic experimental comparisons validate the theoretical findings, and we use real-world data to demonstrate how the method might be used in practice.

Myrl G. Marmarelis, Elizabeth Haddad, Andrew Jesson et al.

Inferring causal effects of continuous-valued treatments from observational data is a crucial task promising to better inform policy- and decision-makers. A critical assumption needed to identify these effects is that all confounding variables -- causal parents of both the treatment and the outcome -- are included as covariates. Unfortunately, given observational data alone, we cannot know with certainty that this criterion is satisfied. Sensitivity analyses provide principled ways to give bounds on causal estimates when confounding variables are hidden. While much attention is focused on sensitivity analyses for discrete-valued treatments, much less is paid to continuous-valued treatments. We present novel methodology to bound both average and conditional average continuous-valued treatment-effect estimates when they cannot be point identified due to hidden confounding. A semi-synthetic benchmark on multiple datasets shows our method giving tighter coverage of the true dose-response curve than a recently proposed continuous sensitivity model and baselines. Finally, we apply our method to a real-world observational case study to demonstrate the value of identifying dose-dependent causal effects.

Maëlys Solal, Andrew Jesson, Yarin Gal et al.

Aerosol-cloud interactions (ACI) include various effects that result from aerosols entering a cloud, and affecting cloud properties. In general, an increase in aerosol concentration results in smaller droplet sizes which leads to larger, brighter, longer-lasting clouds that reflect more sunlight and cool the Earth. The strength of the effect is however heterogeneous, meaning it depends on the surrounding environment, making ACI one of the most uncertain effects in our current climate models. In our work, we use causal machine learning to estimate ACI from satellite observations by reframing the problem as a treatment (aerosol) and outcome (change in droplet radius). We predict the causal effect of aerosol on clouds with uncertainty bounds depending on the unknown factors that may be influencing the impact of aerosol. Of the three climate models evaluated, we find that only one plausibly recreates the trend, lending more credence to its estimate cooling due to ACI.

Claudia Shi, Nicolas Beltran-Velez, Achille Nazaret et al.

Large language models (LLMs) demonstrate surprising capabilities, but we do not understand how they are implemented. One hypothesis suggests that these capabilities are primarily executed by small subnetworks within the LLM, known as circuits. But how can we evaluate this hypothesis? In this paper, we formalize a set of criteria that a circuit is hypothesized to meet and develop a suite of hypothesis tests to evaluate how well circuits satisfy them. The criteria focus on the extent to which the LLM's behavior is preserved, the degree of localization of this behavior, and whether the circuit is minimal. We apply these tests to six circuits described in the research literature. We find that synthetic circuits -- circuits that are hard-coded in the model -- align with the idealized properties. Circuits discovered in Transformer models satisfy the criteria to varying degrees. To facilitate future empirical studies of circuits, we created the \textit{circuitry} package, a wrapper around the \textit{TransformerLens} library, which abstracts away lower-level manipulations of hooks and activations. The software is available at \url{https://github.com/blei-lab/circuitry}.

Arash Mehrjou, Ashkan Soleymani, Andrew Jesson et al.

In vitro cellular experimentation with genetic interventions, using for example CRISPR technologies, is an essential step in early-stage drug discovery and target validation that serves to assess initial hypotheses about causal associations between biological mechanisms and disease pathologies. With billions of potential hypotheses to test, the experimental design space for in vitro genetic experiments is extremely vast, and the available experimental capacity - even at the largest research institutions in the world - pales in relation to the size of this biological hypothesis space. Machine learning methods, such as active and reinforcement learning, could aid in optimally exploring the vast biological space by integrating prior knowledge from various information sources as well as extrapolating to yet unexplored areas of the experimental design space based on available data. However, there exist no standardised benchmarks and data sets for this challenging task and little research has been conducted in this area to date. Here, we introduce GeneDisco, a benchmark suite for evaluating active learning algorithms for experimental design in drug discovery. GeneDisco contains a curated set of multiple publicly available experimental data sets as well as open-source implementations of state-of-the-art active learning policies for experimental design and exploration.

Clare Lyle, Arash Mehrjou, Pascal Notin et al. · deepmind

The discovery of therapeutics to treat genetically-driven pathologies relies on identifying genes involved in the underlying disease mechanisms. Existing approaches search over the billions of potential interventions to maximize the expected influence on the target phenotype. However, to reduce the risk of failure in future stages of trials, practical experiment design aims to find a set of interventions that maximally change a target phenotype via diverse mechanisms. We propose DiscoBAX, a sample-efficient method for maximizing the rate of significant discoveries per experiment while simultaneously probing for a wide range of diverse mechanisms during a genomic experiment campaign. We provide theoretical guarantees of approximate optimality under standard assumptions, and conduct a comprehensive experimental evaluation covering both synthetic as well as real-world experimental design tasks. DiscoBAX outperforms existing state-of-the-art methods for experimental design, selecting effective and diverse perturbations in biological systems.

Andrew Jesson, Yiding Jiang

We demonstrate that recent advances in reinforcement learning (RL) combined with simple architectural changes significantly improves generalization on the ProcGen benchmark. These changes are frame stacking, replacing 2D convolutional layers with 3D convolutional layers, and scaling up the number of convolutional kernels per layer. Experimental results using a single set of hyperparameters across all environments show a 37.9\% reduction in the optimality gap compared to the baseline (from 0.58 to 0.36). This performance matches or exceeds current state-of-the-art methods. The proposed changes are largely orthogonal and therefore complementary to the existing approaches for improving generalization in RL, and our results suggest that further exploration in this direction could yield substantial improvements in addressing generalization challenges in deep reinforcement learning.

Andrew Jesson, Nicolas Beltran-Velez, David Blei

This work is about estimating when a conditional generative model (CGM) can solve an in-context learning (ICL) problem. An in-context learning (ICL) problem comprises a CGM, a dataset, and a prediction task. The CGM could be a multi-modal foundation model; the dataset, a collection of patient histories, test results, and recorded diagnoses; and the prediction task to communicate a diagnosis to a new patient. A Bayesian interpretation of ICL assumes that the CGM computes a posterior predictive distribution over an unknown Bayesian model defining a joint distribution over latent explanations and observable data. From this perspective, Bayesian model criticism is a reasonable approach to assess the suitability of a given CGM for an ICL problem. However, such approaches -- like posterior predictive checks (PPCs) -- often assume that we can sample from the likelihood and posterior defined by the Bayesian model, which are not explicitly given for contemporary CGMs. To address this, we show when ancestral sampling from the predictive distribution of a CGM is equivalent to sampling datasets from the posterior predictive of the assumed Bayesian model. Then we develop the generative predictive $p$-value, which enables PPCs and their cousins for contemporary CGMs. The generative predictive $p$-value can then be used in a statistical decision procedure to determine when the model is appropriate for an ICL problem. Our method only requires generating queries and responses from a CGM and evaluating its response log probability. We empirically evaluate our method on synthetic tabular, imaging, and natural language ICL tasks using large language models.

Andrew Jesson, Nicolas Beltran-Velez, Quentin Chu et al.

This paper presents a method for estimating the hallucination rate for in-context learning (ICL) with generative AI. In ICL, a conditional generative model (CGM) is prompted with a dataset and a prediction question and asked to generate a response. One interpretation of ICL assumes that the CGM computes the posterior predictive of an unknown Bayesian model, which implicitly defines a joint distribution over observable datasets and latent mechanisms. This joint distribution factorizes into two components: the model prior over mechanisms and the model likelihood of datasets given a mechanism. With this perspective, we define a hallucination as a generated response to the prediction question with low model likelihood given the mechanism. We develop a new method that takes an ICL problem and estimates the probability that a CGM will generate a hallucination. Our method only requires generating prediction questions and responses from the CGM and evaluating its response log probability. We empirically evaluate our method using large language models for synthetic regression and natural language ICL tasks.

Andrew Jesson, Panagiotis Tigas, Joost van Amersfoort et al.

Estimating personalized treatment effects from high-dimensional observational data is essential in situations where experimental designs are infeasible, unethical, or expensive. Existing approaches rely on fitting deep models on outcomes observed for treated and control populations. However, when measuring individual outcomes is costly, as is the case of a tumor biopsy, a sample-efficient strategy for acquiring each result is required. Deep Bayesian active learning provides a framework for efficient data acquisition by selecting points with high uncertainty. However, existing methods bias training data acquisition towards regions of non-overlapping support between the treated and control populations. These are not sample-efficient because the treatment effect is not identifiable in such regions. We introduce causal, Bayesian acquisition functions grounded in information theory that bias data acquisition towards regions with overlapping support to maximize sample efficiency for learning personalized treatment effects. We demonstrate the performance of the proposed acquisition strategies on synthetic and semi-synthetic datasets IHDP and CMNIST and their extensions, which aim to simulate common dataset biases and pathologies.

Andrew Jesson, Peter Manshausen, Alyson Douglas et al.

Aerosol-cloud interactions include a myriad of effects that all begin when aerosol enters a cloud and acts as cloud condensation nuclei (CCN). An increase in CCN results in a decrease in the mean cloud droplet size (r$_{e}$). The smaller droplet size leads to brighter, more expansive, and longer lasting clouds that reflect more incoming sunlight, thus cooling the earth. Globally, aerosol-cloud interactions cool the Earth, however the strength of the effect is heterogeneous over different meteorological regimes. Understanding how aerosol-cloud interactions evolve as a function of the local environment can help us better understand sources of error in our Earth system models, which currently fail to reproduce the observed relationships. In this work we use recent non-linear, causal machine learning methods to study the heterogeneous effects of aerosols on cloud droplet radius.

Andreas Kirsch, Sebastian Farquhar, Parmida Atighehchian et al.

We examine a simple stochastic strategy for adapting well-known single-point acquisition functions to allow batch active learning. Unlike acquiring the top-K points from the pool set, score- or rank-based sampling takes into account that acquisition scores change as new data are acquired. This simple strategy for adapting standard single-sample acquisition strategies can even perform just as well as compute-intensive state-of-the-art batch acquisition functions, like BatchBALD or BADGE, while using orders of magnitude less compute. In addition to providing a practical option for machine learning practitioners, the surprising success of the proposed method in a wide range of experimental settings raises a difficult question for the field: when are these expensive batch acquisition methods pulling their weight?

Andrew Jesson, Sören Mindermann, Yarin Gal et al.

We study the problem of learning conditional average treatment effects (CATE) from high-dimensional, observational data with unobserved confounders. Unobserved confounders introduce ignorance -- a level of unidentifiability -- about an individual's response to treatment by inducing bias in CATE estimates. We present a new parametric interval estimator suited for high-dimensional data, that estimates a range of possible CATE values when given a predefined bound on the level of hidden confounding. Further, previous interval estimators do not account for ignorance about the CATE associated with samples that may be underrepresented in the original study, or samples that violate the overlap assumption. Our interval estimator also incorporates model uncertainty so that practitioners can be made aware of out-of-distribution data. We prove that our estimator converges to tight bounds on CATE when there may be unobserved confounding, and assess it using semi-synthetic, high-dimensional datasets.

Joost van Amersfoort, Lewis Smith, Andrew Jesson et al.

Inducing point Gaussian process approximations are often considered a gold standard in uncertainty estimation since they retain many of the properties of the exact GP and scale to large datasets. A major drawback is that they have difficulty scaling to high dimensional inputs. Deep Kernel Learning (DKL) promises a solution: a deep feature extractor transforms the inputs over which an inducing point Gaussian process is defined. However, DKL has been shown to provide unreliable uncertainty estimates in practice. We study why, and show that with no constraints, the DKL objective pushes "far-away" data points to be mapped to the same features as those of training-set points. With this insight we propose to constrain DKL's feature extractor to approximately preserve distances through a bi-Lipschitz constraint, resulting in a feature space favorable to DKL. We obtain a model, DUE, which demonstrates uncertainty quality outperforming previous DKL and other single forward pass uncertainty methods, while maintaining the speed and accuracy of standard neural networks.

Andrew Jesson, Sören Mindermann, Uri Shalit et al.

Recommending the best course of action for an individual is a major application of individual-level causal effect estimation. This application is often needed in safety-critical domains such as healthcare, where estimating and communicating uncertainty to decision-makers is crucial. We introduce a practical approach for integrating uncertainty estimation into a class of state-of-the-art neural network methods used for individual-level causal estimates. We show that our methods enable us to deal gracefully with situations of "no-overlap", common in high-dimensional data, where standard applications of causal effect approaches fail. Further, our methods allow us to handle covariate shift, where test distribution differs to train distribution, common when systems are deployed in practice. We show that when such a covariate shift occurs, correctly modeling uncertainty can keep us from giving overconfident and potentially harmful recommendations. We demonstrate our methodology with a range of state-of-the-art models. Under both covariate shift and lack of overlap, our uncertainty-equipped methods can alert decisions makers when predictions are not to be trusted while outperforming their uncertainty-oblivious counterparts.

Spyridon Bakas, Mauricio Reyes, Andras Jakab et al.

Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e., 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST/RANO criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that underwent gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.

Andrew Jesson, Nicolas Guizard, Sina Hamidi Ghalehjegh et al.

We introduce CASED, a novel curriculum sampling algorithm that facilitates the optimization of deep learning segmentation or detection models on data sets with extreme class imbalance. We evaluate the CASED learning framework on the task of lung nodule detection in chest CT. In contrast to two-stage solutions, wherein nodule candidates are first proposed by a segmentation model and refined by a second detection stage, CASED improves the training of deep nodule segmentation models (e.g. UNet) to the point where state of the art results are achieved using only a trivial detection stage. CASED improves the optimization of deep segmentation models by allowing them to first learn how to distinguish nodules from their immediate surroundings, while continuously adding a greater proportion of difficult-to-classify global context, until uniformly sampling from the empirical data distribution. Using CASED during training yields a minimalist proposal to the lung nodule detection problem that tops the LUNA16 nodule detection benchmark with an average sensitivity score of 88.35%. Furthermore, we find that models trained using CASED are robust to nodule annotation quality by showing that comparable results can be achieved when only a point and radius for each ground truth nodule are provided during training. Finally, the CASED learning framework makes no assumptions with regard to imaging modality or segmentation target and should generalize to other medical imaging problems where class imbalance is a persistent problem.

Andrew Jesson, Cécile Low-Kam, Tanya Nair et al.

The Adversarially Learned Mixture Model (AMM) is a generative model for unsupervised or semi-supervised data clustering. The AMM is the first adversarially optimized method to model the conditional dependence between inferred continuous and categorical latent variables. Experiments on the MNIST and SVHN datasets show that the AMM allows for semantic separation of complex data when little or no labeled data is available. The AMM achieves a state-of-the-art unsupervised clustering error rate of 2.86% on the MNIST dataset. A semi-supervised extension of the AMM yields competitive results on the SVHN dataset.

Xiang Jiang, Mohammad Havaei, Gabriel Chartrand et al.

Current deep learning based text classification methods are limited by their ability to achieve fast learning and generalization when the data is scarce. We address this problem by integrating a meta-learning procedure that uses the knowledge learned across many tasks as an inductive bias towards better natural language understanding. Based on the Model-Agnostic Meta-Learning framework (MAML), we introduce the Attentive Task-Agnostic Meta-Learning (ATAML) algorithm for text classification. The essential difference between MAML and ATAML is in the separation of task-agnostic representation learning and task-specific attentive adaptation. The proposed ATAML is designed to encourage task-agnostic representation learning by way of task-agnostic parameterization and facilitate task-specific adaptation via attention mechanisms. We provide evidence to show that the attention mechanism in ATAML has a synergistic effect on learning performance. In comparisons with models trained from random initialization, pretrained models and meta trained MAML, our proposed ATAML method generalizes better on single-label and multi-label classification tasks in miniRCV1 and miniReuters-21578 datasets.