A collection of the accepted papers for the Human-Centric Representation Learning workshop at AAAI 2024

This non-archival index is not complete, as some accepted papers chose to opt-out of inclusion. The list of all accepted papers is available on the workshop website.

DiscoBAX: Discovery of Optimal Intervention Sets in Genomic Experiment Design

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.

The CausalBench challenge: A machine learning contest for gene network inference from single-cell perturbation data

In drug discovery, mapping interactions between genes within cellular systems is a crucial early step. This helps formulate hypotheses regarding molecular mechanisms that could potentially be targeted by future medicines. The CausalBench Challenge was an initiative to invite the machine learning community to advance the state of the art in constructing gene-gene interaction networks. These networks, derived from large-scale, real-world datasets of single cells under various perturbations, are crucial for understanding the causal mechanisms underlying disease biology. Using the framework provided by the CausalBench benchmark, participants were tasked with enhancing the capacity of the state of the art methods to leverage large-scale genetic perturbation data. This report provides an analysis and summary of the methods submitted during the challenge to give a partial image of the state of the art at the time of the challenge. The winning solutions significantly improved performance compared to previous baselines, establishing a new state of the art for this critical task in biology and medicine.

Multi-omics Prediction from High-content Cellular Imaging with Deep Learning

High-content cellular imaging, transcriptomics, and proteomics data provide rich and complementary views on the molecular layers of biology that influence cellular states and function. However, the biological determinants through which changes in multi-omics measurements influence cellular morphology have not yet been systematically explored, and the degree to which cell imaging could potentially enable the prediction of multi-omics directly from cell imaging data is therefore currently unclear. Here, we address the question of whether it is possible to predict bulk multi-omics measurements directly from cell images using Image2Omics -- a deep learning approach that predicts multi-omics in a cell population directly from high-content images stained with multiplexed fluorescent dyes. We perform an experimental evaluation in gene-edited macrophages derived from human induced pluripotent stem cell (hiPSC) under multiple stimulation conditions and demonstrate that Image2Omics achieves significantly better performance in predicting transcriptomics and proteomics measurements directly from cell images than predictors based on the mean observed training set abundance. We observed significant predictability of abundances for 5903 (22.43%; 95% CI: 8.77%, 38.88%) and 5819 (22.11%; 95% CI: 10.40%, 38.08%) transcripts out of 26137 in M1 and M2-stimulated macrophages respectively and for 1933 (38.77%; 95% CI: 36.94%, 39.85%) and 2055 (41.22%; 95% CI: 39.31%, 42.42%) proteins out of 4986 in M1 and M2-stimulated macrophages respectively. Our results show that some transcript and protein abundances are predictable from cell imaging and that cell imaging may potentially, in some settings and depending on the mechanisms of interest and desired performance threshold, even be a scalable and resource-efficient substitute for multi-omics measurements.

FED-CD: Federated Causal Discovery from Interventional and Observational Data

Causal discovery, the inference of causal relations from data, is a core task of fundamental importance in all scientific domains, and several new machine learning methods for addressing the causal discovery problem have been proposed recently. However, existing machine learning methods for causal discovery typically require that the data used for inference is pooled and available in a centralized location. In many domains of high practical importance, such as in healthcare, data is only available at local data-generating entities (e.g. hospitals in the healthcare context), and cannot be shared across entities due to, among others, privacy and regulatory reasons. In this work, we address the problem of inferring causal structure - in the form of a directed acyclic graph (DAG) - from a distributed data set that contains both observational and interventional data in a privacy-preserving manner by exchanging updates instead of samples. To this end, we introduce a new federated framework, FED-CD, that enables the discovery of global causal structures both when the set of intervened covariates is the same across decentralized entities, and when the set of intervened covariates are potentially disjoint. We perform a comprehensive experimental evaluation on synthetic data that demonstrates that FED-CD enables effective aggregation of decentralized data for causal discovery without direct sample sharing, even when the contributing distributed data sets cover disjoint sets of interventions. Effective methods for causal discovery in distributed data sets could significantly advance scientific discovery and knowledge sharing in important settings, for instance, healthcare, in which sharing of data across local sites is difficult or prohibited.

CausalBench: A Large-scale Benchmark for Network Inference from Single-cell Perturbation Data

Mapping biological mechanisms in cellular systems is a fundamental step in early-stage drug discovery that serves to generate hypotheses on what disease-relevant molecular targets may effectively be modulated by pharmacological interventions. With the advent of high-throughput methods for measuring single-cell gene expression under genetic perturbations, we now have effective means for generating evidence for causal gene-gene interactions at scale. However, inferring graphical networks of the size typically encountered in real-world gene-gene interaction networks is difficult in terms of both achieving and evaluating faithfulness to the true underlying causal graph. Moreover, standardised benchmarks for comparing methods for causal discovery in perturbational single-cell data do not yet exist. Here, we introduce CausalBench - a comprehensive benchmark suite for evaluating network inference methods on large-scale perturbational single-cell gene expression data. CausalBench introduces several biologically meaningful performance metrics and operates on two large, curated and openly available benchmark data sets for evaluating methods on the inference of gene regulatory networks from single-cell data generated under perturbations. With real-world datasets consisting of over \numprint{200000} training samples under interventions, CausalBench could potentially help facilitate advances in causal network inference by providing what is - to the best of our knowledge - the largest openly available test bed for causal discovery from real-world perturbation data to date.

Federated Learning in Multi-Center Critical Care Research: A Systematic Case Study using the eICU Database

Federated learning (FL) has been proposed as a method to train a model on different units without exchanging data. This offers great opportunities in the healthcare sector, where large datasets are available but cannot be shared to ensure patient privacy. We systematically investigate the effectiveness of FL on the publicly available eICU dataset for predicting the survival of each ICU stay. We employ Federated Averaging as the main practical algorithm for FL and show how its performance changes by altering three key hyper-parameters, taking into account that clients can significantly vary in size. We find that in many settings, a large number of local training epochs improves the performance while at the same time reducing communication costs. Furthermore, we outline in which settings it is possible to have only a low number of hospitals participating in each federated update round. When many hospitals with low patient counts are involved, the effect of overfitting can be avoided by decreasing the batchsize. This study thus contributes toward identifying suitable settings for running distributed algorithms such as FL on clinical datasets.

Conditional Generation of Medical Time Series for Extrapolation to Underrepresented Populations

The widespread adoption of electronic health records (EHRs) and subsequent increased availability of longitudinal healthcare data has led to significant advances in our understanding of health and disease with direct and immediate impact on the development of new diagnostics and therapeutic treatment options. However, access to EHRs is often restricted due to their perceived sensitive nature and associated legal concerns, and the cohorts therein typically are those seen at a specific hospital or network of hospitals and therefore not representative of the wider population of patients. Here, we present HealthGen, a new approach for the conditional generation of synthetic EHRs that maintains an accurate representation of real patient characteristics, temporal information and missingness patterns. We demonstrate experimentally that HealthGen generates synthetic cohorts that are significantly more faithful to real patient EHRs than the current state-of-the-art, and that augmenting real data sets with conditionally generated cohorts of underrepresented subpopulations of patients can significantly enhance the generalisability of models derived from these data sets to different patient populations. Synthetic conditionally generated EHRs could help increase the accessibility of longitudinal healthcare data sets and improve the generalisability of inferences made from these data sets to underrepresented populations.

GeneDisco: A Benchmark for Experimental Design in Drug Discovery

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.