An Inclusive Foundation Model for Generalizable Cytogenetics in Precision Oncology

Chromosome analysis is vital for diagnosing genetic disorders and guiding cancer therapy decisions through the identification of somatic clonal aberrations. However, developing an AI model are hindered by the overwhelming complexity and diversity of chromosomal abnormalities, requiring extensive annotation efforts, while automated methods remain task-specific and lack generalizability due to the scarcity of comprehensive datasets spanning diverse resource conditions. Here, we introduce CHROMA, a foundation model for cytogenomics, designed to overcome these challenges by learning generalizable representations of chromosomal abnormalities. Pre-trained on over 84,000 specimens (~4 million chromosomal images) via self-supervised learning, CHROMA outperforms other methods across all types of abnormalities, even when trained on fewer labelled data and more imbalanced datasets. By facilitating comprehensive mapping of instability and clonal leisons across various aberration types, CHROMA offers a scalable and generalizable solution for reliable and automated clinical analysis, reducing the annotation workload for experts and advancing precision oncology through the early detection of rare genomic abnormalities, enabling broad clinical AI applications and making advanced genomic analysis more accessible.

A Model-Based Approach to Imitation Learning through Multi-Step Predictions

Imitation learning is a widely used approach for training agents to replicate expert behavior in complex decision-making tasks. However, existing methods often struggle with compounding errors and limited generalization, due to the inherent challenge of error correction and the distribution shift between training and deployment. In this paper, we present a novel model-based imitation learning framework inspired by model predictive control, which addresses these limitations by integrating predictive modeling through multi-step state predictions. Our method outperforms traditional behavior cloning numerical benchmarks, demonstrating superior robustness to distribution shift and measurement noise both in available data and during execution. Furthermore, we provide theoretical guarantees on the sample complexity and error bounds of our method, offering insights into its convergence properties.

Mitigating Timbre Leakage with Universal Semantic Mapping Residual Block for Voice Conversion

Voice conversion (VC) transforms source speech into a target voice by preserving the content. However, timbre information from the source speaker is inherently embedded in the content representations, causing significant timbre leakage and reducing similarity to the target speaker. To address this, we introduce a residual block to a content extractor. The residual block consists of two weighted branches: 1) universal semantic dictionary based Content Feature Re-expression (CFR) module, supplying timbre-free content representation. 2) skip connection to the original content layer, providing complementary fine-grained information. In the CFR module, each dictionary entry in the universal semantic dictionary represents a phoneme class, computed statistically using speech from multiple speakers, creating a stable, speaker-independent semantic set. We introduce a CFR method to obtain timbre-free content representations by expressing each content frame as a weighted linear combination of dictionary entries using corresponding phoneme posteriors as weights. Extensive experiments across various VC frameworks demonstrate that our approach effectively mitigates timbre leakage and significantly improves similarity to the target speaker.

Integrating Large Language Models with Human Expertise for Disease Detection in Electronic Health Records

Objective: Electronic health records (EHR) are widely available to complement administrative data-based disease surveillance and healthcare performance evaluation. Defining conditions from EHR is labour-intensive and requires extensive manual labelling of disease outcomes. This study developed an efficient strategy based on advanced large language models to identify multiple conditions from EHR clinical notes. Methods: We linked a cardiac registry cohort in 2015 with an EHR system in Alberta, Canada. We developed a pipeline that leveraged a generative large language model (LLM) to analyze, understand, and interpret EHR notes by prompts based on specific diagnosis, treatment management, and clinical guidelines. The pipeline was applied to detect acute myocardial infarction (AMI), diabetes, and hypertension. The performance was compared against clinician-validated diagnoses as the reference standard and widely adopted International Classification of Diseases (ICD) codes-based methods. Results: The study cohort accounted for 3,088 patients and 551,095 clinical notes. The prevalence was 55.4%, 27.7%, 65.9% and for AMI, diabetes, and hypertension, respectively. The performance of the LLM-based pipeline for detecting conditions varied: AMI had 88% sensitivity, 63% specificity, and 77% positive predictive value (PPV); diabetes had 91% sensitivity, 86% specificity, and 71% PPV; and hypertension had 94% sensitivity, 32% specificity, and 72% PPV. Compared with ICD codes, the LLM-based method demonstrated improved sensitivity and negative predictive value across all conditions. The monthly percentage trends from the detected cases by LLM and reference standard showed consistent patterns.

Adaptive Wavelet Filters as Practical Texture Feature Amplifiers for Parkinson's Disease Screening in OCT

Parkinson's disease (PD) is a prevalent neurodegenerative disorder globally. The eye's retina is an extension of the brain and has great potential in PD screening. Recent studies have suggested that texture features extracted from retinal layers can be adopted as biomarkers for PD diagnosis under optical coherence tomography (OCT) images. Frequency domain learning techniques can enhance the feature representations of deep neural networks (DNNs) by decomposing frequency components involving rich texture features. Additionally, previous works have not exploited texture features for automated PD screening in OCT. Motivated by the above analysis, we propose a novel Adaptive Wavelet Filter (AWF) that serves as the Practical Texture Feature Amplifier to fully leverage the merits of texture features to boost the PD screening performance of DNNs with the aid of frequency domain learning. Specifically, AWF first enhances texture feature representation diversities via channel mixer, then emphasizes informative texture feature representations with the well-designed adaptive wavelet filtering token mixer. By combining the AWFs with the DNN stem, AWFNet is constructed for automated PD screening. Additionally, we introduce a novel Balanced Confidence (BC) Loss by mining the potential of sample-wise predicted probabilities of all classes and class frequency prior, to further boost the PD screening performance and trustworthiness of AWFNet. The extensive experiments manifest the superiority of our AWFNet and BC over state-of-the-art methods in terms of PD screening performance and trustworthiness.

Primal-Dual Spectral Representation for Off-policy Evaluation

Off-policy evaluation (OPE) is one of the most fundamental problems in reinforcement learning (RL) to estimate the expected long-term payoff of a given target policy with only experiences from another behavior policy that is potentially unknown. The distribution correction estimation (DICE) family of estimators have advanced the state of the art in OPE by breaking the curse of horizon. However, the major bottleneck of applying DICE estimators lies in the difficulty of solving the saddle-point optimization involved, especially with neural network implementations. In this paper, we tackle this challenge by establishing a linear representation of value function and stationary distribution correction ratio, i.e., primal and dual variables in the DICE framework, using the spectral decomposition of the transition operator. Such primal-dual representation not only bypasses the non-convex non-concave optimization in vanilla DICE, therefore enabling an computational efficient algorithm, but also paves the way for more efficient utilization of historical data. We highlight that our algorithm, SpectralDICE, is the first to leverage the linear representation of primal-dual variables that is both computation and sample efficient, the performance of which is supported by a rigorous theoretical sample complexity guarantee and a thorough empirical evaluation on various benchmarks.

Scalable spectral representations for network multiagent control

Network Markov Decision Processes (MDPs), a popular model for multi-agent control, pose a significant challenge to efficient learning due to the exponential growth of the global state-action space with the number of agents. In this work, utilizing the exponential decay property of network dynamics, we first derive scalable spectral local representations for network MDPs, which induces a network linear subspace for the local $Q$-function of each agent. Building on these local spectral representations, we design a scalable algorithmic framework for continuous state-action network MDPs, and provide end-to-end guarantees for the convergence of our algorithm. Empirically, we validate the effectiveness of our scalable representation-based approach on two benchmark problems, and demonstrate the advantages of our approach over generic function approximation approaches to representing the local $Q$-functions.

Distributed Thompson sampling under constrained communication

In Bayesian optimization, a black-box function is maximized via the use of a surrogate model. We apply distributed Thompson sampling, using a Gaussian process as a surrogate model, to approach the multi-agent Bayesian optimization problem. In our distributed Thompson sampling implementation, each agent receives sampled points from neighbors, where the communication network is encoded in a graph; each agent utilizes a Gaussian process to model the objective function. We demonstrate a theoretical bound on Bayesian Simple Regret, where the bound depends on the size of the largest complete subgraph of the communication graph. Unlike in batch Bayesian optimization, this bound is applicable in cases where the communication graph amongst agents is constrained. When compared to sequential Thompson sampling, our bound guarantees faster convergence with respect to time as long as there is a fully connected subgraph of at least two agents. We confirm the efficacy of our algorithm with numerical simulations on traditional optimization test functions, illustrating the significance of graph connectivity on improving regret convergence.

Drift to Remember

Lifelong learning in artificial intelligence (AI) aims to mimic the biological brain's ability to continuously learn and retain knowledge, yet it faces challenges such as catastrophic forgetting. Recent neuroscience research suggests that neural activity in biological systems undergoes representational drift, where neural responses evolve over time, even with consistent inputs and tasks. We hypothesize that representational drift can alleviate catastrophic forgetting in AI during new task acquisition. To test this, we introduce DriftNet, a network designed to constantly explore various local minima in the loss landscape while dynamically retrieving relevant tasks. This approach ensures efficient integration of new information and preserves existing knowledge. Experimental studies in image classification and natural language processing demonstrate that DriftNet outperforms existing models in lifelong learning. Importantly, DriftNet is scalable in handling a sequence of tasks such as sentiment analysis and question answering using large language models (LLMs) with billions of parameters on a single Nvidia A100 GPU. DriftNet efficiently updates LLMs using only new data, avoiding the need for full dataset retraining. Tested on GPT-2 and RoBERTa, DriftNet is a robust, cost-effective solution for lifelong learning in LLMs. This study not only advances AI systems to emulate biological learning, but also provides insights into the adaptive mechanisms of biological neural systems, deepening our understanding of lifelong learning in nature.

Model-in-the-Loop (MILO): Accelerating Multimodal AI Data Annotation with LLMs

The growing demand for AI training data has transformed data annotation into a global industry, but traditional approaches relying on human annotators are often time-consuming, labor-intensive, and prone to inconsistent quality. We propose the Model-in-the-Loop (MILO) framework, which integrates AI/ML models into the annotation process. Our research introduces a collaborative paradigm that leverages the strengths of both professional human annotators and large language models (LLMs). By employing LLMs as pre-annotation and real-time assistants, and judges on annotator responses, MILO enables effective interaction patterns between human annotators and LLMs. Three empirical studies on multimodal data annotation demonstrate MILO's efficacy in reducing handling time, improving data quality, and enhancing annotator experiences. We also introduce quality rubrics for flexible evaluation and fine-grained feedback on open-ended annotations. The MILO framework has implications for accelerating AI/ML development, reducing reliance on human annotation alone, and promoting better alignment between human and machine values.