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Discrimination and calibration represent two important properties of survival analysis, with the former assessing the model's ability to accurately rank subjects and the latter evaluating the alignment of predicted outcomes with actual events. With their distinct nature, it is hard for survival models to simultaneously optimize both of them especially as many previous results found improving calibration tends to diminish discrimination performance. This paper introduces a novel approach utilizing conformal regression that can improve a model's calibration without degrading discrimination. We provide theoretical guarantees for the above claim, and rigorously validate the efficiency of our approach across 11 real-world datasets, showcasing its practical applicability and robustness in diverse scenarios., Comment: Accepted to ICML 2024; 37 pages, 19 figures

This research paper explores ways to apply Federated Learning (FL) and Differential Privacy (DP) techniques to population-scale Electrocardiogram (ECG) data. The study learns a multi-label ECG classification model using FL and DP based on 1,565,849 ECG tracings from 7 hospitals in Alberta, Canada. The FL approach allowed collaborative model training without sharing raw data between hospitals while building robust ECG classification models for diagnosing various cardiac conditions. These accurate ECG classification models can facilitate the diagnoses while preserving patient confidentiality using FL and DP techniques. Our results show that the performance achieved using our implementation of the FL approach is comparable to that of the pooled approach, where the model is trained over the aggregating data from all hospitals. Furthermore, our findings suggest that hospitals with limited ECGs for training can benefit from adopting the FL model compared to single-site training. In addition, this study showcases the trade-off between model performance and data privacy by employing DP during model training. Our code is available at https://github.com/vikhyatt/Hospital-FL-DP., Comment: Accepted for ICMHI 2024

Forecasting the occurrence and absence of novel disease outbreaks is essential for disease management. Here, we develop a general model, with no real-world training data, that accurately forecasts outbreaks and non-outbreaks. We propose a novel framework, using a feature-based time series classification method to forecast outbreaks and non-outbreaks. We tested our methods on synthetic data from a Susceptible-Infected-Recovered model for slowly changing, noisy disease dynamics. Outbreak sequences give a transcritical bifurcation within a specified future time window, whereas non-outbreak (null bifurcation) sequences do not. We identified incipient differences in time series of infectives leading to future outbreaks and non-outbreaks. These differences are reflected in 22 statistical features and 5 early warning signal indicators. Classifier performance, given by the area under the receiver-operating curve, ranged from 0.99 for large expanding windows of training data to 0.7 for small rolling windows. Real-world performances of classifiers were tested on two empirical datasets, COVID-19 data from Singapore and SARS data from Hong Kong, with two classifiers exhibiting high accuracy. In summary, we showed that there are statistical features that distinguish outbreak and non-outbreak sequences long before outbreaks occur. We could detect these differences in synthetic and real-world data sets, well before potential outbreaks occur.

The timely detection of disease outbreaks through reliable early warning signals (EWSs) is indispensable for effective public health mitigation strategies. Nevertheless, the intricate dynamics of real-world disease spread, often influenced by diverse sources of noise and limited data in the early stages of outbreaks, pose a significant challenge in developing reliable EWSs, as the performance of existing indicators varies with extrinsic and intrinsic noises. Here, we address the challenge of modeling disease when the measurements are corrupted by additive white noise, multiplicative environmental noise, and demographic noise into a standard epidemic mathematical model. To navigate the complexities introduced by these noise sources, we employ a deep learning algorithm that provides EWS in infectious disease outbreak by training on noise-induced disease-spreading models. The indicator's effectiveness is demonstrated through its application to real-world COVID-19 cases in Edmonton and simulated time series derived from diverse disease spread models affected by noise. Notably, the indicator captures an impending transition in a time series of disease outbreaks and outperforms existing indicators. This study contributes to advancing early warning capabilities by addressing the intricate dynamics inherent in real-world disease spread, presenting a promising avenue for enhancing public health preparedness and response efforts.

A survival dataset describes a set of instances (e.g. patients) and provides, for each, either the time until an event (e.g. death), or the censoring time (e.g. when lost to follow-up - which is a lower bound on the time until the event). We consider the challenge of survival prediction: learning, from such data, a predictive model that can produce an individual survival distribution for a novel instance. Many contemporary methods of survival prediction implicitly assume that the event and censoring distributions are independent conditional on the instance's covariates - a strong assumption that is difficult to verify (as we observe only one outcome for each instance) and which can induce significant bias when it does not hold. This paper presents a parametric model of survival that extends modern non-linear survival analysis by relaxing the assumption of conditional independence. On synthetic and semi-synthetic data, our approach significantly improves estimates of survival distributions compared to the standard that assumes conditional independence in the data., Comment: 23 pages, 7 figures

One straightforward metric to evaluate a survival prediction model is based on the Mean Absolute Error (MAE) -- the average of the absolute difference between the time predicted by the model and the true event time, over all subjects. Unfortunately, this is challenging because, in practice, the test set includes (right) censored individuals, meaning we do not know when a censored individual actually experienced the event. In this paper, we explore various metrics to estimate MAE for survival datasets that include (many) censored individuals. Moreover, we introduce a novel and effective approach for generating realistic semi-synthetic survival datasets to facilitate the evaluation of metrics. Our findings, based on the analysis of the semi-synthetic datasets, reveal that our proposed metric (MAE using pseudo-observations) is able to rank models accurately based on their performance, and often closely matches the true MAE -- in particular, is better than several alternative methods., Comment: Accepted to ICML 2023

The alignment of tissue between histopathological whole-slide-images (WSI) is crucial for research and clinical applications. Advances in computing, deep learning, and availability of large WSI datasets have revolutionised WSI analysis. Therefore, the current state-of-the-art in WSI registration is unclear. To address this, we conducted the ACROBAT challenge, based on the largest WSI registration dataset to date, including 4,212 WSIs from 1,152 breast cancer patients. The challenge objective was to align WSIs of tissue that was stained with routine diagnostic immunohistochemistry to its H&E-stained counterpart. We compare the performance of eight WSI registration algorithms, including an investigation of the impact of different WSI properties and clinical covariates. We find that conceptually distinct WSI registration methods can lead to highly accurate registration performances and identify covariates that impact performances across methods. These results establish the current state-of-the-art in WSI registration and guide researchers in selecting and developing methods.

Classical epidemiological models assume homogeneous populations. There have been important extensions to model heterogeneous populations, when the identity of the sub-populations is known, such as age group or geographical location. Here, we propose two new methods to model the number of people infected with COVID-19 over time, each as a linear combination of latent sub-populations -- i.e., when we do not know which person is in which sub-population, and the only available observations are the aggregates across all sub-populations. Method #1 is a dictionary-based approach, which begins with a large number of pre-defined sub-population models (each with its own starting time, shape, etc), then determines the (positive) weight of small (learned) number of sub-populations. Method #2 is a mixture-of-$M$ fittable curves, where $M$, the number of sub-populations to use, is given by the user. Both methods are compatible with any parametric model; here we demonstrate their use with first (a)~Gaussian curves and then (b)~SIR trajectories. We empirically show the performance of the proposed methods, first in (i) modeling the observed data and then in (ii) forecasting the number of infected people 1 to 4 weeks in advance. Across 187 countries, we show that the dictionary approach had the lowest mean absolute percentage error and also the lowest variance when compared with classical SIR models and moreover, it was a strong baseline that outperforms many of the models developed for COVID-19 forecasting., Comment: 14 pages, 8 figures, submitted to Frontiers in Big Data

Pandemic outbreaks such as COVID-19 occur unexpectedly, and need immediate action due to their potential devastating consequences on global health. Point-of-care routine assessments such as electrocardiogram (ECG), can be used to develop prediction models for identifying individuals at risk. However, there is often too little clinically-annotated medical data, especially in early phases of a pandemic, to develop accurate prediction models. In such situations, historical pre-pandemic health records can be utilized to estimate a preliminary model, which can then be fine-tuned based on limited available pandemic data. This study shows this approach -- pre-train deep learning models with pre-pandemic data -- can work effectively, by demonstrating substantial performance improvement over three different COVID-19 related diagnostic and prognostic prediction tasks. Similar transfer learning strategies can be useful for developing timely artificial intelligence solutions in future pandemic outbreaks., Comment: Accepted for NeurIPS 2022 TS4H workshop

Electrocardiogram (ECG) abnormalities are linked to cardiovascular diseases, but may also occur in other non-cardiovascular conditions such as mental, neurological, metabolic and infectious conditions. However, most of the recent success of deep learning (DL) based diagnostic predictions in selected patient cohorts have been limited to a small set of cardiac diseases. In this study, we use a population-based dataset of >250,000 patients with >1000 medical conditions and >2 million ECGs to identify a wide range of diseases that could be accurately diagnosed from the patient's first in-hospital ECG. Our DL models uncovered 128 diseases and 68 disease categories with strong discriminative performance., Comment: Accepted in Medical Imaging meets NeurIPS 2021 https://www.cse.cuhk.edu.hk/~qdou/public/medneurips2021/88_ECG_for_high-throughput_screening_of_multiple_diseases_final_version.pdf

A predictor, $f_A : X \to Y$, learned with data from a source domain (A) might not be accurate on a target domain (B) when their distributions are different. Domain adaptation aims to reduce the negative effects of this distribution mismatch. Here, we analyze the case where $P_A(Y\ |\ X) \neq P_B(Y\ |\ X)$, $P_A(X) \neq P_B(X)$ but $P_A(Y) = P_B(Y)$; where there are affine transformations of $X$ that makes all distributions equivalent. We propose an approach to project the source and target domains into a lower-dimensional, common space, by (1) projecting the domains into the eigenvectors of the empirical covariance matrices of each domain, then (2) finding an orthogonal matrix that minimizes the maximum mean discrepancy between the projections of both domains. For arbitrary affine transformations, there is an inherent unidentifiability problem when performing unsupervised domain adaptation that can be alleviated in the semi-supervised case. We show the effectiveness of our approach in simulated data and in binary digit classification tasks, obtaining improvements up to 48% accuracy when correcting for the domain shift in the data.

Estimating causal effects from observational data (at either an individual -- or a population -- level) is critical for making many types of decisions. One approach to address this task is to learn decomposed representations of the underlying factors of data; this becomes significantly more challenging when there are confounding factors (which influence both the cause and the effect). In this paper, we take a generative approach that builds on the recent advances in Variational Auto-Encoders to simultaneously learn those underlying factors as well as the causal effects. We propose a progressive sequence of models, where each improves over the previous one, culminating in the Hybrid model. Our empirical results demonstrate that the performance of all three proposed models are superior to both state-of-the-art discriminative as well as other generative approaches in the literature.

Accurate forecasts of the number of newly infected people during an epidemic are critical for making effective timely decisions. This paper addresses this challenge using the SIMLR model, which incorporates machine learning (ML) into the epidemiological SIR model. For each region, SIMLR tracks the changes in the policies implemented at the government level, which it uses to estimate the time-varying parameters of an SIR model for forecasting the number of new infections 1- to 4-weeks in advance.It also forecasts the probability of changes in those government policies at each of these future times, which is essential for the longer-range forecasts. We applied SIMLR to data from regions in Canada and in the United States,and show that its MAPE (mean average percentage error) performance is as good as SOTA forecasting models, with the added advantage of being an interpretable model. We expect that this approach will be useful not only for forecasting COVID-19 infections, but also in predicting the evolution of other infectious diseases.

Deep learning approaches often require huge datasets to achieve good generalization. This complicates its use in tasks like image-based medical diagnosis, where the small training datasets are usually insufficient to learn appropriate data representations. For such sensitive tasks it is also important to provide the confidence in the predictions. Here, we propose a way to learn and use probabilistic labels to train accurate and calibrated deep networks from relatively small datasets. We observe gains of up to 22% in the accuracy of models trained with these labels, as compared with traditional approaches, in three classification tasks: diagnosis of hip dysplasia, fatty liver, and glaucoma. The outputs of models trained with probabilistic labels are calibrated, allowing the interpretation of its predictions as proper probabilities. We anticipate this approach will apply to other tasks where few training instances are available and expert knowledge can be encoded as probabilities., Comment: To appear in the Proceedings of the 24 th International Conference on Artificial Intelligence and Statistics (AISTATS) 2021, San Diego,California, USA. PMLR: Volume 130

Multi-voxel pattern analysis (MVPA) learns predictive models from task-based functional magnetic resonance imaging (fMRI) data, for distinguishing when subjects are performing different cognitive tasks -- e.g., watching movies or making decisions. MVPA works best with a well-designed feature set and an adequate sample size. However, most fMRI datasets are noisy, high-dimensional, expensive to collect, and with small sample sizes. Further, training a robust, generalized predictive model that can analyze homogeneous cognitive tasks provided by multi-site fMRI datasets has additional challenges. This paper proposes the Shared Space Transfer Learning (SSTL) as a novel transfer learning (TL) approach that can functionally align homogeneous multi-site fMRI datasets, and so improve the prediction performance in every site. SSTL first extracts a set of common features for all subjects in each site. It then uses TL to map these site-specific features to a site-independent shared space in order to improve the performance of the MVPA. SSTL uses a scalable optimization procedure that works effectively for high-dimensional fMRI datasets. The optimization procedure extracts the common features for each site by using a single-iteration algorithm and maps these site-specific common features to the site-independent shared space. We evaluate the effectiveness of the proposed method for transferring between various cognitive tasks. Our comprehensive experiments validate that SSTL achieves superior performance to other state-of-the-art analysis techniques., Comment: 34th Conference on Neural Information Processing Systems (NeurIPS 2020), Vancouver, Canada. The Supplementary Material: https://www.yousefnezhad.com/publications/NeurIPS2020_Paper4157_SuppMat.zip

Counterfactual reasoning is an important paradigm applicable in many fields, such as healthcare, economics, and education. In this work, we propose a novel method to address the issue of \textit{selection bias}. We learn two groups of latent random variables, where one group corresponds to variables that only cause selection bias, and the other group is relevant for outcome prediction. They are learned by an auto-encoder where an additional regularized loss based on Pearson Correlation Coefficient (PCC) encourages the de-correlation between the two groups of random variables. This allows for explicitly alleviating selection bias by only keeping the latent variables that are relevant for estimating individual treatment effects. Experimental results on a synthetic toy dataset and a benchmark dataset show that our algorithm is able to achieve state-of-the-art performance and improve the result of its counterpart that does not explicitly model the selection bias., Comment: NeurIPS 2019 Workshop on "Do the right thing": machine learning and causal inference for improved decision making

In many real-world applications, we want to exploit multiple source datasets of similar tasks to learn a model for a different but related target dataset -- e.g., recognizing characters of a new font using a set of different fonts. While most recent research has considered ad-hoc combination rules to address this problem, we extend previous work on domain discrepancy minimization to develop a finite-sample generalization bound, and accordingly propose a theoretically justified optimization procedure. The algorithm we develop, Domain AggRegation Network (DARN), is able to effectively adjust the weight of each source domain during training to ensure relevant domains are given more importance for adaptation. We evaluate the proposed method on real-world sentiment analysis and digit recognition datasets and show that DARN can significantly outperform the state-of-the-art alternatives.

Accurate models of patient survival probabilities provide important information to clinicians prescribing care for life-threatening and terminal ailments. A recently developed class of models - known as individual survival distributions (ISDs) - produces patient-specific survival functions that offer greater descriptive power of patient outcomes than was previously possible. Unfortunately, at the time of writing, ISD models almost universally lack uncertainty quantification. In this paper, we demonstrate that an existing method for estimating simultaneous prediction intervals from samples can easily be adapted for patient-specific survival curve analysis and yields accurate results. Furthermore, we introduce both a modification to the existing method and a novel method for estimating simultaneous prediction intervals and show that they offer competitive performance. It is worth emphasizing that these methods are not limited to survival analysis and can be applied in any context in which sampling the distribution of interest is tractable. Code is available at https://github.com/ssokota/spie ., Comment: 7 pages, 7 figures, IJCAI 19

Patients with Type I Diabetes (T1D) must take insulin injections to prevent the serious long term effects of hyperglycemia - high blood glucose (BG). Patients must also be careful not to inject too much insulin because this could induce hypoglycemia (low BG), which can potentially be fatal. Patients therefore follow a "regimen" that determines how much insulin to inject at certain times. Current methods for managing this disease require adjusting the patient's regimen over time based on the disease's behavior (recorded in the patient's diabetes diary). If we can accurately predict a patient's future BG values from his/her current features (e.g., predicting today's lunch BG value given today's diabetes diary entry for breakfast, including insulin injections, and perhaps earlier entries), then it is relatively easy to produce an effective regimen. This study explores the challenges of BG modeling by applying several machine learning algorithms and various data preprocessing variations (corresponding to 312 [learner, preprocessed-dataset] combinations), to a new T1D dataset containing 29 601 entries from 47 different patients. Our most accurate predictor is a weighted ensemble of two Gaussian Process Regression models, which achieved an errL1 loss of 2.70 mmol/L (48.65 mg/dl). This was an unexpectedly poor result given that one can obtain an errL1 of 2.91 mmol/L (52.43 mg/dl) using the naive approach of simply predicting the patient's average BG. For each of data-variant/model combination we report several evaluation metrics, including glucose-specific metrics, and find similarly disappointing results (the best model was only incrementally better than the simplest measure). These results suggest that the diabetes diary data that is typically collected may not be sufficient to produce accurate BG prediction models; additional data may be necessary to build accurate BG prediction models.

Cancer is one of the leading cause of death, worldwide. Many believe that genomic data will enable us to better predict the survival time of these patients, which will lead to better, more personalized treatment options and patient care. As standard survival prediction models have a hard time coping with the high-dimensionality of such gene expression (GE) data, many projects use some dimensionality reduction techniques to overcome this hurdle. We introduce a novel methodology, inspired by topic modeling from the natural language domain, to derive expressive features from the high-dimensional GE data. There, a document is represented as a mixture over a relatively small number of topics, where each topic corresponds to a distribution over the words; here, to accommodate the heterogeneity of a patient's cancer, we represent each patient (~document) as a mixture over cancer-topics, where each cancer-topic is a mixture over GE values (~words). This required some extensions to the standard LDA model eg: to accommodate the "real-valued" expression values - leading to our novel "discretized" Latent Dirichlet Allocation (dLDA) procedure. We initially focus on the METABRIC dataset, which describes breast cancer patients using the r=49,576 GE values, from microarrays. Our results show that our approach provides survival estimates that are more accurate than standard models, in terms of the standard Concordance measure. We then validate this approach by running it on the Pan-kidney (KIPAN) dataset, over r=15,529 GE values - here using the mRNAseq modality - and find that it again achieves excellent results. In both cases, we also show that the resulting model is calibrated, using the recent "D-calibrated" measure. These successes, in two different cancer types and expression modalities, demonstrates the generality, and the effectiveness, of this approach.

An accurate model of a patient's individual survival distribution can help determine the appropriate treatment for terminal patients. Unfortunately, risk scores (e.g., from Cox Proportional Hazard models) do not provide survival probabilities, single-time probability models (e.g., the Gail model, predicting 5 year probability) only provide for a single time point, and standard Kaplan-Meier survival curves provide only population averages for a large class of patients meaning they are not specific to individual patients. This motivates an alternative class of tools that can learn a model which provides an individual survival distribution which gives survival probabilities across all times - such as extensions to the Cox model, Accelerated Failure Time, an extension to Random Survival Forests, and Multi-Task Logistic Regression. This paper first motivates such "individual survival distribution" (ISD) models, and explains how they differ from standard models. It then discusses ways to evaluate such models - namely Concordance, 1-Calibration, Brier score, and various versions of L1-loss - and then motivates and defines a novel approach "D-Calibration", which determines whether a model's probability estimates are meaningful. We also discuss how these measures differ, and use them to evaluate several ISD prediction tools, over a range of survival datasets., Comment: 34 pages (main text), 12 figures

Smart systems that can accurately diagnose patients with mental disorders and identify effective treatments based on brain functional imaging data are of great applicability and are gaining much attention. Most previous machine learning studies use hand-designed features, such as functional connectivity, which does not maintain the potential useful information in the spatial relationship between brain regions and the temporal profile of the signal in each region. Here we propose a new method based on recurrent-convolutional neural networks to automatically learn useful representations from segments of 4-D fMRI recordings. Our goal is to exploit both spatial and temporal information in the functional MRI movie (at the whole-brain voxel level) for identifying patients with schizophrenia., Comment: To be published as a workshop paper at NIPS 2017 Machine Learning for Health (ML4H)

We propose a Laplace approximation that creates a stochastic unit from any smooth monotonic activation function, using only Gaussian noise. This paper investigates the application of this stochastic approximation in training a family of Restricted Boltzmann Machines (RBM) that are closely linked to Bregman divergences. This family, that we call exponential family RBM (Exp-RBM), is a subset of the exponential family Harmoniums that expresses family members through a choice of smooth monotonic non-linearity for each neuron. Using contrastive divergence along with our Gaussian approximation, we show that Exp-RBM can learn useful representations using novel stochastic units., Comment: AISTATS 2016

Boolean matrix factorization and Boolean matrix completion from noisy observations are desirable unsupervised data-analysis methods due to their interpretability, but hard to perform due to their NP-hardness. We treat these problems as maximum a posteriori inference problems in a graphical model and present a message passing approach that scales linearly with the number of observations and factors. Our empirical study demonstrates that message passing is able to recover low-rank Boolean matrices, in the boundaries of theoretically possible recovery and compares favorably with state-of-the-art in real-world applications, such collaborative filtering with large-scale Boolean data.