arXiv subjects

Patrick Schwab

Publications and source records attributed to Patrick Schwab.

31 records · Page 2Linked to original sources

arXiv2021

GeneDisco: A Benchmark for Experimental Design in Drug Discovery

In vitro cellular experimentation with genetic interventions, using for example CRISPR technologies, is an essential step in early-stage drug discovery and target validation that serves to assess initial hypotheses about causal associations between biological mechanisms and disease pathologies. With billions of potential hypotheses to test, the experimental design space for in vitro genetic experiments is extremely vast, and the available experimental capacity - even at the largest research institutions in the world - pales in relation to the size of this biological hypothesis space. Machine learning methods, such as active and reinforcement learning, could aid in optimally exploring the vast biological space by integrating prior knowledge from various information sources as well as extrapolating to yet unexplored areas of the experimental design space based on available data. However, there exist no standardised benchmarks and data sets for this challenging task and little research has been conducted in this area to date. Here, we introduce GeneDisco, a benchmark suite for evaluating active learning algorithms for experimental design in drug discovery. GeneDisco contains a curated set of multiple publicly available experimental data sets as well as open-source implementations of state-of-the-art active learning policies for experimental design and exploration.

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arXiv2021

Overcoming Barriers to Data Sharing with Medical Image Generation: A Comprehensive Evaluation

Privacy concerns around sharing personally identifiable information are a major practical barrier to data sharing in medical research. However, in many cases, researchers have no interest in a particular individual's information but rather aim to derive insights at the level of cohorts. Here, we utilize Generative Adversarial Networks (GANs) to create derived medical imaging datasets consisting entirely of synthetic patient data. The synthetic images ideally have, in aggregate, similar statistical properties to those of a source dataset but do not contain sensitive personal information. We assess the quality of synthetic data generated by two GAN models for chest radiographs with 14 different radiology findings and brain computed tomography (CT) scans with six types of intracranial hemorrhages. We measure the synthetic image quality by the performance difference of predictive models trained on either the synthetic or the real dataset. We find that synthetic data performance disproportionately benefits from a reduced number of unique label combinations. Our open-source benchmark also indicates that at low number of samples per class, label overfitting effects start to dominate GAN training. We additionally conducted a reader study in which trained radiologists do not perform better than random on discriminating between synthetic and real medical images for intermediate levels of resolutions. In accordance with our benchmark results, the classification accuracy of radiologists increases at higher spatial resolution levels. Our study offers valuable guidelines and outlines practical conditions under which insights derived from synthetic medical images are similar to those that would have been derived from real imaging data. Our results indicate that synthetic data sharing may be an attractive and privacy-preserving alternative to sharing real patient-level data in the right settings.

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arXiv2021

NCoRE: Neural Counterfactual Representation Learning for Combinations of Treatments

Estimating an individual's potential response to interventions from observational data is of high practical relevance for many domains, such as healthcare, public policy or economics. In this setting, it is often the case that combinations of interventions may be applied simultaneously, for example, multiple prescriptions in healthcare or different fiscal and monetary measures in economics. However, existing methods for counterfactual inference are limited to settings in which actions are not used simultaneously. Here, we present Neural Counterfactual Relation Estimation (NCoRE), a new method for learning counterfactual representations in the combination treatment setting that explicitly models cross-treatment interactions. NCoRE is based on a novel branched conditional neural representation that includes learnt treatment interaction modulators to infer the potential causal generative process underlying the combination of multiple treatments. Our experiments show that NCoRE significantly outperforms existing state-of-the-art methods for counterfactual treatment effect estimation that do not account for the effects of combining multiple treatments across several synthetic, semi-synthetic and real-world benchmarks.

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arXiv2020

Learning Counterfactual Representations for Estimating Individual Dose-Response Curves

Estimating what would be an individual's potential response to varying levels of exposure to a treatment is of high practical relevance for several important fields, such as healthcare, economics and public policy. However, existing methods for learning to estimate counterfactual outcomes from observational data are either focused on estimating average dose-response curves, or limited to settings with only two treatments that do not have an associated dosage parameter. Here, we present a novel machine-learning approach towards learning counterfactual representations for estimating individual dose-response curves for any number of treatments with continuous dosage parameters with neural networks. Building on the established potential outcomes framework, we introduce performance metrics, model selection criteria, model architectures, and open benchmarks for estimating individual dose-response curves. Our experiments show that the methods developed in this work set a new state-of-the-art in estimating individual dose-response.

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arXiv2020

Clinical Predictive Models for COVID-19: Systematic Study

Coronavirus Disease 2019 (COVID-19) is a rapidly emerging respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the rapid human-to-human transmission of SARS-CoV-2, many healthcare systems are at risk of exceeding their healthcare capacities, in particular in terms of SARS-CoV-2 tests, hospital and intensive care unit (ICU) beds and mechanical ventilators. Predictive algorithms could potentially ease the strain on healthcare systems by identifying those who are most likely to receive a positive SARS-CoV-2 test, be hospitalised or admitted to the ICU. Here, we study clinical predictive models that estimate, using machine learning and based on routinely collected clinical data, which patients are likely to receive a positive SARS-CoV-2 test, require hospitalisation or intensive care. To evaluate the predictive performance of our models, we perform a retrospective evaluation on clinical and blood analysis data from a cohort of 5644 patients. Our experimental results indicate that our predictive models identify (i) patients that test positive for SARS-CoV-2 a priori at a sensitivity of 75% (95% CI: 67%, 81%) and a specificity of 49% (95% CI: 46%, 51%), (ii) SARS-CoV-2 positive patients that require hospitalisation with 0.92 AUC (95% CI: 0.81, 0.98), and (iii) SARS-CoV-2 positive patients that require critical care with 0.98 AUC (95% CI: 0.95, 1.00). In addition, we determine which clinical features are predictive to what degree for each of the aforementioned clinical tasks. Our results indicate that predictive models trained on routinely collected clinical data could be used to predict clinical pathways for COVID-19, and therefore help inform care and prioritise resources.

cs.LG↗

arXiv2020

Real-time Prediction of COVID-19 related Mortality using Electronic Health Records

Coronavirus Disease 2019 (COVID-19) is an emerging respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with rapid human-to-human transmission and a high case fatality rate particularly in older patients. Due to the exponential growth of infections, many healthcare systems across the world are under pressure to care for increasing amounts of at-risk patients. Given the high number of infected patients, identifying patients with the highest mortality risk early is critical to enable effective intervention and optimal prioritisation of care. Here, we present the COVID-19 Early Warning System (CovEWS), a clinical risk scoring system for assessing COVID-19 related mortality risk. CovEWS provides continuous real-time risk scores for individual patients with clinically meaningful predictive performance up to 192 hours (8 days) in advance, and is automatically derived from patients' electronic health records (EHRs) using machine learning. We trained and evaluated CovEWS using de-identified data from a cohort of 66430 COVID-19 positive patients seen at over 69 healthcare institutions in the United States (US), Australia, Malaysia and India amounting to an aggregated total of over 2863 years of patient observation time. On an external test cohort of 5005 patients, CovEWS predicts COVID-19 related mortality from $78.8\%$ ($95\%$ confidence interval [CI]: $76.0$, $84.7\%$) to $69.4\%$ ($95\%$ CI: $57.6, 75.2\%$) specificity at a sensitivity greater than $95\%$ between respectively 1 and 192 hours prior to observed mortality events - significantly outperforming existing generic and COVID-19 specific clinical risk scores. CovEWS could enable clinicians to intervene at an earlier stage, and may therefore help in preventing or mitigating COVID-19 related mortality.

stat.AP↗

arXiv2020

A Deep Learning Approach to Diagnosing Multiple Sclerosis from Smartphone Data

Multiple sclerosis (MS) affects the central nervous system with a wide range of symptoms. MS can, for example, cause pain, changes in mood and fatigue, and may impair a person's movement, speech and visual functions. Diagnosis of MS typically involves a combination of complex clinical assessments and tests to rule out other diseases with similar symptoms. New technologies, such as smartphone monitoring in free-living conditions, could potentially aid in objectively assessing the symptoms of MS by quantifying symptom presence and intensity over long periods of time. Here, we present a deep-learning approach to diagnosing MS from smartphone-derived digital biomarkers that uses a novel combination of a multilayer perceptron with neural soft attention to improve learning of patterns in long-term smartphone monitoring data. Using data from a cohort of 774 participants, we demonstrate that our deep-learning models are able to distinguish between people with and without MS with an area under the receiver operating characteristic curve of 0.88 (95% CI: 0.70, 0.88). Our experimental results indicate that digital biomarkers derived from smartphone data could in the future be used as additional diagnostic criteria for MS.

cs.CY↗

arXiv2019

CXPlain: Causal Explanations for Model Interpretation under Uncertainty

Feature importance estimates that inform users about the degree to which given inputs influence the output of a predictive model are crucial for understanding, validating, and interpreting machine-learning models. However, providing fast and accurate estimates of feature importance for high-dimensional data, and quantifying the uncertainty of such estimates remain open challenges. Here, we frame the task of providing explanations for the decisions of machine-learning models as a causal learning task, and train causal explanation (CXPlain) models that learn to estimate to what degree certain inputs cause outputs in another machine-learning model. CXPlain can, once trained, be used to explain the target model in little time, and enables the quantification of the uncertainty associated with its feature importance estimates via bootstrap ensembling. We present experiments that demonstrate that CXPlain is significantly more accurate and faster than existing model-agnostic methods for estimating feature importance. In addition, we confirm that the uncertainty estimates provided by CXPlain ensembles are strongly correlated with their ability to accurately estimate feature importance on held-out data.

cs.LG↗

arXiv2019

Perfect Match: A Simple Method for Learning Representations For Counterfactual Inference With Neural Networks

Learning representations for counterfactual inference from observational data is of high practical relevance for many domains, such as healthcare, public policy and economics. Counterfactual inference enables one to answer "What if...?" questions, such as "What would be the outcome if we gave this patient treatment $t_1$?". However, current methods for training neural networks for counterfactual inference on observational data are either overly complex, limited to settings with only two available treatments, or both. Here, we present Perfect Match (PM), a method for training neural networks for counterfactual inference that is easy to implement, compatible with any architecture, does not add computational complexity or hyperparameters, and extends to any number of treatments. PM is based on the idea of augmenting samples within a minibatch with their propensity-matched nearest neighbours. Our experiments demonstrate that PM outperforms a number of more complex state-of-the-art methods in inferring counterfactual outcomes across several benchmarks, particularly in settings with many treatments.

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arXiv2018

PhoneMD: Learning to Diagnose Parkinson's Disease from Smartphone Data

Parkinson's disease is a neurodegenerative disease that can affect a person's movement, speech, dexterity, and cognition. Clinicians primarily diagnose Parkinson's disease by performing a clinical assessment of symptoms. However, misdiagnoses are common. One factor that contributes to misdiagnoses is that the symptoms of Parkinson's disease may not be prominent at the time the clinical assessment is performed. Here, we present a machine-learning approach towards distinguishing between people with and without Parkinson's disease using long-term data from smartphone-based walking, voice, tapping and memory tests. We demonstrate that our attentive deep-learning models achieve significant improvements in predictive performance over strong baselines (area under the receiver operating characteristic curve = 0.85) in data from a cohort of 1853 participants. We also show that our models identify meaningful features in the input data. Our results confirm that smartphone data collected over extended periods of time could in the future potentially be used as a digital biomarker for the diagnosis of Parkinson's disease.

q-bio.NC↗

arXiv2018

Granger-causal Attentive Mixtures of Experts: Learning Important Features with Neural Networks

Knowledge of the importance of input features towards decisions made by machine-learning models is essential to increase our understanding of both the models and the underlying data. Here, we present a new approach to estimating feature importance with neural networks based on the idea of distributing the features of interest among experts in an attentive mixture of experts (AME). AMEs use attentive gating networks trained with a Granger-causal objective to learn to jointly produce accurate predictions as well as estimates of feature importance in a single model. Our experiments show (i) that the feature importance estimates provided by AMEs compare favourably to those provided by state-of-the-art methods, (ii) that AMEs are significantly faster at estimating feature importance than existing methods, and (iii) that the associations discovered by AMEs are consistent with those reported by domain experts.

cs.LG↗

arXiv2018

Not to Cry Wolf: Distantly Supervised Multitask Learning in Critical Care

Patients in the intensive care unit (ICU) require constant and close supervision. To assist clinical staff in this task, hospitals use monitoring systems that trigger audiovisual alarms if their algorithms indicate that a patient's condition may be worsening. However, current monitoring systems are extremely sensitive to movement artefacts and technical errors. As a result, they typically trigger hundreds to thousands of false alarms per patient per day - drowning the important alarms in noise and adding to the exhaustion of clinical staff. In this setting, data is abundantly available, but obtaining trustworthy annotations by experts is laborious and expensive. We frame the problem of false alarm reduction from multivariate time series as a machine-learning task and address it with a novel multitask network architecture that utilises distant supervision through multiple related auxiliary tasks in order to reduce the number of expensive labels required for training. We show that our approach leads to significant improvements over several state-of-the-art baselines on real-world ICU data and provide new insights on the importance of task selection and architectural choices in distantly supervised multitask learning.

cs.LG↗

arXiv2017

Beat by Beat: Classifying Cardiac Arrhythmias with Recurrent Neural Networks

With tens of thousands of electrocardiogram (ECG) records processed by mobile cardiac event recorders every day, heart rhythm classification algorithms are an important tool for the continuous monitoring of patients at risk. We utilise an annotated dataset of 12,186 single-lead ECG recordings to build a diverse ensemble of recurrent neural networks (RNNs) that is able to distinguish between normal sinus rhythms, atrial fibrillation, other types of arrhythmia and signals that are too noisy to interpret. In order to ease learning over the temporal dimension, we introduce a novel task formulation that harnesses the natural segmentation of ECG signals into heartbeats to drastically reduce the number of time steps per sequence. Additionally, we extend our RNNs with an attention mechanism that enables us to reason about which heartbeats our RNNs focus on to make their decisions. Through the use of attention, our model maintains a high degree of interpretability, while also achieving state-of-the-art classification performance with an average F1 score of 0.79 on an unseen test set (n=3,658).

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