Abstract:Large Language Models (LLMs) have become pivotal in advancing natural language processing, yet their potential to perpetuate biases poses significant concerns. This paper introduces a new framework employing Direct Preference Optimization (DPO) to mitigate gender, racial, and religious biases in LLM-generated English text. By developing a loss function that favors less biased over biased completions, our approach cultivates a preference for respectful and non-discriminatory language in LLMs. We also contribute a manually designed dataset for training LLMs to recognize and correct biases. This dataset encompasses a diverse range of prompts paired with both biased and unbiased completions. Implementing this approach on the Microsoft Phi-2 model, we demonstrate substantial reductions in biased outputs as our model outperforms the baseline model on almost all bias benchmarks. Our model also achieves better performance compared to other open-source models on most benchmarks. By reducing biases in the language generated by the model, our study marks a significant step towards developing more ethical and socially responsible LLMs. We publicly release BiasDPO dataset on HuggingFace.
Abstract:We propose a deep generative approach using latent temporal processes for modeling and holistically analyzing complex disease trajectories, with a particular focus on Systemic Sclerosis (SSc). We aim to learn temporal latent representations of the underlying generative process that explain the observed patient disease trajectories in an interpretable and comprehensive way. To enhance the interpretability of these latent temporal processes, we develop a semi-supervised approach for disentangling the latent space using established medical knowledge. By combining the generative approach with medical definitions of different characteristics of SSc, we facilitate the discovery of new aspects of the disease. We show that the learned temporal latent processes can be utilized for further data analysis and clinical hypothesis testing, including finding similar patients and clustering SSc patient trajectories into novel sub-types. Moreover, our method enables personalized online monitoring and prediction of multivariate time series with uncertainty quantification.
Abstract:Large Language Models (LLMs) have demonstrated potential in assisting with Register Transfer Level (RTL) design tasks. Nevertheless, there remains to be a significant gap in benchmarks that accurately reflect the complexity of real-world RTL projects. To address this, this paper presents RTL-Repo, a benchmark specifically designed to evaluate LLMs on large-scale RTL design projects. RTL-Repo includes a comprehensive dataset of more than 4000 Verilog code samples extracted from public GitHub repositories, with each sample providing the full context of the corresponding repository. We evaluate several state-of-the-art models on the RTL-Repo benchmark, including GPT-4, GPT-3.5, Starcoder2, alongside Verilog-specific models like VeriGen and RTLCoder, and compare their performance in generating Verilog code for complex projects. The RTL-Repo benchmark provides a valuable resource for the hardware design community to assess and compare LLMs' performance in real-world RTL design scenarios and train LLMs specifically for Verilog code generation in complex, multi-file RTL projects. RTL-Repo is open-source and publicly available on Github.
Abstract:The identification of phenotypes within complex diseases or syndromes is a fundamental component of precision medicine, which aims to adapt healthcare to individual patient characteristics. Postoperative delirium (POD) is a complex neuropsychiatric condition with significant heterogeneity in its clinical manifestations and underlying pathophysiology. We hypothesize that POD comprises several distinct phenotypes, which cannot be directly observed in clinical practice. Identifying these phenotypes could enhance our understanding of POD pathogenesis and facilitate the development of targeted prevention and treatment strategies. In this paper, we propose an approach that combines supervised machine learning for personalized POD risk prediction with unsupervised clustering techniques to uncover potential POD phenotypes. We first demonstrate our approach using synthetic data, where we simulate patient cohorts with predefined phenotypes based on distinct sets of informative features. We aim to mimic any clinical disease with our synthetic data generation method. By training a predictive model and applying SHAP, we show that clustering patients in the SHAP feature importance space successfully recovers the true underlying phenotypes, outperforming clustering in the raw feature space. We then present a case study using real-world data from a cohort of elderly surgical patients. The results showcase the utility of our approach in uncovering clinically relevant subtypes of complex disorders like POD, paving the way for more precise and personalized treatment strategies.
Abstract:In this paper, we propose a deep generative time series approach using latent temporal processes for modeling and holistically analyzing complex disease trajectories. We aim to find meaningful temporal latent representations of an underlying generative process that explain the observed disease trajectories in an interpretable and comprehensive way. To enhance the interpretability of these latent temporal processes, we develop a semi-supervised approach for disentangling the latent space using established medical concepts. By combining the generative approach with medical knowledge, we leverage the ability to discover novel aspects of the disease while integrating medical concepts into the model. We show that the learned temporal latent processes can be utilized for further data analysis and clinical hypothesis testing, including finding similar patients and clustering the disease into new sub-types. Moreover, our method enables personalized online monitoring and prediction of multivariate time series including uncertainty quantification. We demonstrate the effectiveness of our approach in modeling systemic sclerosis, showcasing the potential of our machine learning model to capture complex disease trajectories and acquire new medical knowledge.
Abstract:Human genetic diseases often arise from point mutations, emphasizing the critical need for precise genome editing techniques. Among these, base editing stands out as it allows targeted alterations at the single nucleotide level. However, its clinical application is hindered by low editing efficiency and unintended mutations, necessitating extensive trial-and-error experimentation in the laboratory. To speed up this process, we present an attention-based two-stage machine learning model that learns to predict the likelihood of all possible editing outcomes for a given genomic target sequence. We further propose a multi-task learning schema to jointly learn multiple base editors (i.e. variants) at once. Our model's predictions consistently demonstrated a strong correlation with the actual experimental results on multiple datasets and base editor variants. These results provide further validation for the models' capacity to enhance and accelerate the process of refining base editing designs.
Abstract:Irregular multivariate time series data is prevalent in the clinical and healthcare domains. It is characterized by time-wise and feature-wise irregularities, making it challenging for machine learning methods to work with. To solve this, we introduce a new model architecture composed of two modules: (1) DLA, a Dynamic Local Attention mechanism that uses learnable queries and feature-specific local windows when computing the self-attention operation. This results in aggregating irregular time steps raw input within each window to a harmonized regular latent space representation while taking into account the different features' sampling rates. (2) A hierarchical MLP mixer that processes the output of DLA through multi-scale patching to leverage information at various scales for the downstream tasks. Our approach outperforms state-of-the-art methods on three real-world datasets, including the latest clinical MIMIC IV dataset.
Abstract:We propose a novel framework that combines deep generative time series models with decision theory for generating personalized treatment strategies. It leverages historical patient trajectory data to jointly learn the generation of realistic personalized treatment and future outcome trajectories through deep generative time series models. In particular, our framework enables the generation of novel multivariate treatment strategies tailored to the personalized patient history and trained for optimal expected future outcomes based on conditional expected utility maximization. We demonstrate our framework by generating personalized insulin treatment strategies and blood glucose predictions for hospitalized diabetes patients, showcasing the potential of our approach for generating improved personalized treatment strategies. Keywords: deep generative model, probabilistic decision support, personalized treatment generation, insulin and blood glucose prediction
Abstract:Contrastive learning methods have shown an impressive ability to learn meaningful representations for image or time series classification. However, these methods are less effective for time series forecasting, as optimization of instance discrimination is not directly applicable to predicting the future state from the history context. Moreover, the construction of positive and negative pairs in current technologies strongly relies on specific time series characteristics, restricting their generalization across diverse types of time series data. To address these limitations, we propose SimTS, a simple representation learning approach for improving time series forecasting by learning to predict the future from the past in the latent space. SimTS does not rely on negative pairs or specific assumptions about the characteristics of the particular time series. Our extensive experiments on several benchmark time series forecasting datasets show that SimTS achieves competitive performance compared to existing contrastive learning methods. Furthermore, we show the shortcomings of the current contrastive learning framework used for time series forecasting through a detailed ablation study. Overall, our work suggests that SimTS is a promising alternative to other contrastive learning approaches for time series forecasting.
Abstract:Background: Federated learning methods offer the possibility of training machine learning models on privacy-sensitive data sets, which cannot be easily shared. Multiple regulations pose strict requirements on the storage and usage of healthcare data, leading to data being in silos (i.e. locked-in at healthcare facilities). The application of federated algorithms on these datasets could accelerate disease diagnostic, drug development, as well as improve patient care. Methods: We present an extensive evaluation of the impact of different federation and differential privacy techniques when training models on the open-source MIMIC-III dataset. We analyze a set of parameters influencing a federated model performance, namely data distribution (homogeneous and heterogeneous), communication strategies (communication rounds vs. local training epochs), federation strategies (FedAvg vs. FedProx). Furthermore, we assess and compare two differential privacy (DP) techniques during model training: a stochastic gradient descent-based differential privacy algorithm (DP-SGD), and a sparse vector differential privacy technique (DP-SVT). Results: Our experiments show that extreme data distributions across sites (imbalance either in the number of patients or the positive label ratios between sites) lead to a deterioration of model performance when trained using the FedAvg strategy. This issue is resolved when using FedProx with the use of appropriate hyperparameter tuning. Furthermore, the results show that both differential privacy techniques can reach model performances similar to those of models trained without DP, however at the expense of a large quantifiable privacy leakage. Conclusions: We evaluate empirically the benefits of two federation strategies and propose optimal strategies for the choice of parameters when using differential privacy techniques.