In conventional machine learning (ML) approaches applied to electroencephalography (EEG), this is often a limited focus, isolating specific brain activities occurring across disparate temporal scales (from transient spikes in milliseconds to seizures lasting minutes) and spatial scales (from localized high-frequency oscillations to global sleep activity). This siloed approach limits the development EEG ML models that exhibit multi-scale electrophysiological understanding and classification capabilities. Moreover, typical ML EEG approaches utilize black-box approaches, limiting their interpretability and trustworthiness in clinical contexts. Thus, we propose EEG-GPT, a unifying approach to EEG classification that leverages advances in large language models (LLM). EEG-GPT achieves excellent performance comparable to current state-of-the-art deep learning methods in classifying normal from abnormal EEG in a few-shot learning paradigm utilizing only 2% of training data. Furthermore, it offers the distinct advantages of providing intermediate reasoning steps and coordinating specialist EEG tools across multiple scales in its operation, offering transparent and interpretable step-by-step verification, thereby promoting trustworthiness in clinical contexts.
Drawing from discussions at the inaugural DMLR workshop at ICML 2023 and meetings prior, in this report we outline the relevance of community engagement and infrastructure development for the creation of next-generation public datasets that will advance machine learning science. We chart a path forward as a collective effort to sustain the creation and maintenance of these datasets and methods towards positive scientific, societal and business impact.
The drug development pipeline for a new compound can last 10-20 years and cost over 10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on biomedical knowledge graph representations have recently yielded new drug repurposing hypotheses. In this study, we present a novel, disease-specific hypergraph representation learning technique to derive contextual embeddings of biological pathways of various lengths but that all start at any given drug and all end at the disease of interest. Further, we extend this method to multi-disease hypergraphs. To determine the repurposing potential of each of the 1,522 drugs, we derive drug-specific distributions of cosine similarity values and ultimately consider the median for ranking. Cosine similarity values are computed between (1) all biological pathways starting at the considered drug and ending at the disease of interest and (2) all biological pathways starting at drugs currently prescribed against that disease and ending at the disease of interest. We illustrate our approach with Alzheimer's disease (AD) and two of its risk factors: hypertension (HTN) and type 2 diabetes (T2D). We compare each drug's rank across four hypergraph settings (single- or multi-disease): AD only, AD + HTN, AD + T2D, and AD + HTN + T2D. Notably, our framework led to the identification of two promising drugs whose repurposing potential was significantly higher in hypergraphs combining two diseases: dapagliflozin (antidiabetic; moved up, from top 32$\%$ to top 7$\%$, across all considered drugs) and debrisoquine (antihypertensive; moved up, from top 76$\%$ to top 23$\%$). Our approach serves as a hypothesis generation tool, to be paired with a validation pipeline relying on laboratory experiments and semi-automated parsing of the biomedical literature.
We investigate the problem of machine learning-based (ML) predictive inference on individual treatment effects (ITEs). Previous work has focused primarily on developing ML-based meta-learners that can provide point estimates of the conditional average treatment effect (CATE); these are model-agnostic approaches for combining intermediate nuisance estimates to produce estimates of CATE. In this paper, we develop conformal meta-learners, a general framework for issuing predictive intervals for ITEs by applying the standard conformal prediction (CP) procedure on top of CATE meta-learners. We focus on a broad class of meta-learners based on two-stage pseudo-outcome regression and develop a stochastic ordering framework to study their validity. We show that inference with conformal meta-learners is marginally valid if their (pseudo outcome) conformity scores stochastically dominate oracle conformity scores evaluated on the unobserved ITEs. Additionally, we prove that commonly used CATE meta-learners, such as the doubly-robust learner, satisfy a model- and distribution-free stochastic (or convex) dominance condition, making their conformal inferences valid for practically-relevant levels of target coverage. Whereas existing procedures conduct inference on nuisance parameters (i.e., potential outcomes) via weighted CP, conformal meta-learners enable direct inference on the target parameter (ITE). Numerical experiments show that conformal meta-learners provide valid intervals with competitive efficiency while retaining the favorable point estimation properties of CATE meta-learners.
We present DiffInfinite, a hierarchical diffusion model that generates arbitrarily large histological images while preserving long-range correlation structural information. Our approach first generates synthetic segmentation masks, subsequently used as conditions for the high-fidelity generative diffusion process. The proposed sampling method can be scaled up to any desired image size while only requiring small patches for fast training. Moreover, it can be parallelized more efficiently than previous large-content generation methods while avoiding tiling artefacts. The training leverages classifier-free guidance to augment a small, sparsely annotated dataset with unlabelled data. Our method alleviates unique challenges in histopathological imaging practice: large-scale information, costly manual annotation, and protective data handling. The biological plausibility of DiffInfinite data is validated in a survey by ten experienced pathologists as well as a downstream segmentation task. Furthermore, the model scores strongly on anti-copying metrics which is beneficial for the protection of patient data.
Most medical treatment decisions are sequential in nature. Hence, there is substantial hope that reinforcement learning may make it possible to formulate precise data-driven treatment plans. However, a key challenge for most applications in this field is the sparse nature of primarily mortality-based reward functions, leading to decreased stability of offline estimates. In this work, we introduce a deep Q-learning approach able to obtain more reliable critical care policies. This method integrates relevant but noisy intermediate biomarker signals into the reward specification, without compromising the optimization of the main outcome of interest (e.g. patient survival). We achieve this by first pruning the action set based on all available rewards, and second training a final model based on the sparse main reward but with a restricted action set. By disentangling accurate and approximated rewards through action pruning, potential distortions of the main objective are minimized, all while enabling the extraction of valuable information from intermediate signals that can guide the learning process. We evaluate our method in both off-policy and offline settings using simulated environments and real health records of patients in intensive care units. Our empirical results indicate that pruning significantly reduces the size of the action space while staying mostly consistent with the actions taken by physicians, outperforming the current state-of-the-art offline reinforcement learning method conservative Q-learning. Our work is a step towards developing reliable policies by effectively harnessing the wealth of available information in data-intensive critical care environments.