Medical research, particularly in predicting patient outcomes, heavily relies on medical time series data extracted from Electronic Health Records (EHR), which provide extensive information on patient histories. Despite rigorous examination, labeling errors are inevitable and can significantly impede accurate predictions of patient outcome. To address this challenge, we propose an \textbf{A}ttention-based Learning Framework with Dynamic \textbf{C}alibration and Augmentation for \textbf{T}ime series Noisy \textbf{L}abel \textbf{L}earning (ACTLL). This framework leverages a two-component Beta mixture model to identify the certain and uncertain sets of instances based on the fitness distribution of each class, and it captures global temporal dynamics while dynamically calibrating labels from the uncertain set or augmenting confident instances from the certain set. Experimental results on large-scale EHR datasets eICU and MIMIC-IV-ED, and several benchmark datasets from the UCR and UEA repositories, demonstrate that our model ACTLL has achieved state-of-the-art performance, especially under high noise levels.
Multi-omics research has enhanced our understanding of cancer heterogeneity and progression. Investigating molecular data through multi-omics approaches is crucial for unraveling the complex biological mechanisms underlying cancer, thereby enabling more effective diagnosis, treatment, and prevention strategies. However, predicting patient outcomes through the integration of all available multi-omics data is still an under-study research direction. Here, we present SeNMo, a foundation model that has been trained on multi-omics data across 33 cancer types. SeNMo is particularly efficient in handling multi-omics data characterized by high-width and low-length attributes. We trained SeNMo for the task of overall survival of patients using pan-cancer multi-omics data involving 33 cancer sites from the GDC. The training multi-omics data includes gene expression, DNA methylation, miRNA expression, DNA mutations, protein expression modalities, and clinical data. SeNMo was validated on two independent cohorts: Moffitt Cancer Center and CPTAC lung squamous cell carcinoma. We evaluated the model's performance in predicting patient's overall survival using the C-Index. SeNMo performed consistently well in the training regime, reflected by the validation C-Index of 0.76 on GDC's public data. In the testing regime, SeNMo performed with a C-Index of 0.758 on a held-out test set. The model showed an average accuracy of 99.8% on the task of classifying the primary cancer type on the pan-cancer test cohort. SeNMo demonstrated robust performance on the classification task of predicting the primary cancer type of patients. SeNMo further demonstrated significant performance in predicting tertiary lymph structures from multi-omics data, showing generalizability across cancer types, molecular data types, and clinical endpoints.
Human tissue and its constituent cells form a microenvironment that is fundamentally three-dimensional (3D). However, the standard-of-care in pathologic diagnosis involves selecting a few two-dimensional (2D) sections for microscopic evaluation, risking sampling bias and misdiagnosis. Diverse methods for capturing 3D tissue morphologies have been developed, but they have yet had little translation to clinical practice; manual and computational evaluations of such large 3D data have so far been impractical and/or unable to provide patient-level clinical insights. Here we present Modality-Agnostic Multiple instance learning for volumetric Block Analysis (MAMBA), a deep-learning-based platform for processing 3D tissue images from diverse imaging modalities and predicting patient outcomes. Archived prostate cancer specimens were imaged with open-top light-sheet microscopy or microcomputed tomography and the resulting 3D datasets were used to train risk-stratification networks based on 5-year biochemical recurrence outcomes via MAMBA. With the 3D block-based approach, MAMBA achieves an area under the receiver operating characteristic curve (AUC) of 0.86 and 0.74, superior to 2D traditional single-slice-based prognostication (AUC of 0.79 and 0.57), suggesting superior prognostication with 3D morphological features. Further analyses reveal that the incorporation of greater tissue volume improves prognostic performance and mitigates risk prediction variability from sampling bias, suggesting the value of capturing larger extents of heterogeneous 3D morphology. With the rapid growth and adoption of 3D spatial biology and pathology techniques by researchers and clinicians, MAMBA provides a general and efficient framework for 3D weakly supervised learning for clinical decision support and can help to reveal novel 3D morphological biomarkers for prognosis and therapeutic response.
Recent work on predicting patient outcomes in the Intensive Care Unit (ICU) has focused heavily on the physiological time series data, largely ignoring sparse data such as diagnoses and medications. When they are included, they are usually concatenated in the late stages of a model, which may struggle to learn from rarer disease patterns. Instead, we propose a strategy to exploit diagnoses as relational information by connecting similar patients in a graph. To this end, we propose LSTM-GNN for patient outcome prediction tasks: a hybrid model combining Long Short-Term Memory networks (LSTMs) for extracting temporal features and Graph Neural Networks (GNNs) for extracting the patient neighbourhood information. We demonstrate that LSTM-GNNs outperform the LSTM-only baseline on length of stay prediction tasks on the eICU database. More generally, our results indicate that exploiting information from neighbouring patient cases using graph neural networks is a promising research direction, yielding tangible returns in supervised learning performance on Electronic Health Records.
The pressure of ever-increasing patient demand and budget restrictions make hospital bed management a daily challenge for clinical staff. Most critical is the efficient allocation of resource-heavy Intensive Care Unit (ICU) beds to the patients who need life support. Central to solving this problem is knowing for how long the current set of ICU patients are likely to stay in the unit. In this work, we propose a new deep learning model based on the combination of temporal convolution and pointwise (1x1) convolution, to solve the length of stay prediction task on the eICU and MIMIC-IV critical care datasets. The model - which we refer to as Temporal Pointwise Convolution (TPC) - is specifically designed to mitigate common challenges with Electronic Health Records, such as skewness, irregular sampling and missing data. In doing so, we have achieved significant performance benefits of 18-68% (metric and dataset dependent) over the commonly used Long-Short Term Memory (LSTM) network, and the multi-head self-attention network known as the Transformer. By adding mortality prediction as a side-task, we can improve performance further still, resulting in a mean absolute deviation of 1.55 days (eICU) and 2.28 days (MIMIC-IV) on predicting remaining length of stay.
We present a proxy dataset of vital signs with class labels indicating patient transitions from the ward to intensive care units called Ward2ICU. Patient privacy is protected using a Wasserstein Generative Adversarial Network to implicitly learn an approximation of the data distribution, allowing us to sample synthetic data. The quality of data generation is assessed directly on the binary classification task by comparing specificity and sensitivity of an LSTM classifier on proxy and original datasets. We initialize a discussion of unintentionally disclosing commercial sensitive information and propose a solution for a special case through class label balancing
Medical practitioners use survival models to explore and understand the relationships between patients' covariates (e.g. clinical and genetic features) and the effectiveness of various treatment options. Standard survival models like the linear Cox proportional hazards model require extensive feature engineering or prior medical knowledge to model treatment interaction at an individual level. While nonlinear survival methods, such as neural networks and survival forests, can inherently model these high-level interaction terms, they have yet to be shown as effective treatment recommender systems. We introduce DeepSurv, a Cox proportional hazards deep neural network and state-of-the-art survival method for modeling interactions between a patient's covariates and treatment effectiveness in order to provide personalized treatment recommendations. We perform a number of experiments training DeepSurv on simulated and real survival data. We demonstrate that DeepSurv performs as well as or better than other state-of-the-art survival models and validate that DeepSurv successfully models increasingly complex relationships between a patient's covariates and their risk of failure. We then show how DeepSurv models the relationship between a patient's features and effectiveness of different treatment options to show how DeepSurv can be used to provide individual treatment recommendations. Finally, we train DeepSurv on real clinical studies to demonstrate how it's personalized treatment recommendations would increase the survival time of a set of patients. The predictive and modeling capabilities of DeepSurv will enable medical researchers to use deep neural networks as a tool in their exploration, understanding, and prediction of the effects of a patient's characteristics on their risk of failure.