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.Comment: AAAI Conference on Artificial Intelligence 201

Deep learning for precision medicine

As a result of the recent trend towards digitization, an increasing amount of information is recorded in clinics and hospitals, and this increasingly overwhelms the human decision maker. This issue is one of the main reasons why Machine Learning (ML) is gaining attention in the medical domain, since ML algorithms can make use of all the available information to predict the most likely future events that will occur to each individual patient. Physicians can include these predictions in their decision processes which can lead to improved outcomes. Eventually ML can also be the basis for a decision support system that provides personalized recommendations for each individual patient. It is also worth noticing that medical datasets are becoming both longer (i.e. we have more samples collected through time) and wider (i.e. we store more variables). There- fore we need to use ML algorithms capable of modelling complex relationships among a big number of time-evolving variables. A kind of models that can capture very complex relationships are Deep Neural Networks, which have proven to be successful in other areas of ML, like for example Language Modelling, which is a use case that has some some similarities with the medical use case. However, the medical domain has a set of characteristics that make it an almost unique scenario: multiple events can occur at the same time, there are multiple sequences (i.e. multiple patients), each sequence has an associated set of static variables, both inputs and outputs can be a combination of different data types, etc. For these reasons we need to develop approaches specifically designed for the medical use case. In this work we design and develop different kind of models based on Neural Networks that are suitable for modelling medical datasets. Besides, we tackle different medical tasks and datasets, showing which models work best in each case. The first dataset we use is one collected from patients that suffered from kidney failure. The data was collected in the Charité hospital in Berlin and it is the largest data collection of its kind in Europe. Once the kidney has failed, patients face a lifelong treatment and periodic visits to the clinic for the rest of their lives. Until the hospital finds a new kidney for the patient, he or she must attend to the clinic multiple times per week in order to receive dialysis, which is a treatment that replaces many of the functions of the kidney. After the transplant has been performed, the patient receives immunosuppressive therapy to avoid the rejection of the transplanted kidney. Patients must be periodically controlled to check the status of the kidney, adjust the treatment and take care of associated diseases, such as those that arise due to the immunosuppressive therapy. This dataset started being recorded more than 30 years ago and it is composed of more than 4000 patients that underwent a renal transplantation or are waiting for it. The database has been the basis for many studies in the past. Our first goal with the nephrology dataset is to develop a system to predict the next events that will be recorded in the electronic medical record of each patient, and thus to develop the basis for a future clinical decision support system. Specifically, we model three aspects of the patient evolution: medication prescriptions, laboratory tests ordered and laboratory test results. Besides, there are a set of endpoints that can happen after a transplantation and it would be very valuable for the physicians to be able to know beforehand when one of these is going to happen. Specifically, we also predict whether the patient will die, the transplant will be rejected, or the transplant will be lost. For each visit that a patient makes to the clinic, we anticipate which of those three events (if any) will occur both within 6 months and 12 months after the visit. The second dataset that we use in this thesis is the one collected by the MEmind Wellness Tracker, which contains information related to psychiatric patients. Suicide is the second leading cause of death in the 15-29 years age group, and its prevention is one of the top public health priorities. Traditionally, psychiatric patients have been assessed by self-reports, but these su↵er from recall bias. To improve data quantity and quality, the MEmind Wellness Tracker provides a mobile application that enables patients to send daily reports about their status. Thus, this application enables physicians to get information about patients in their natural environments. Therefore this dataset contains sequential information generated by the MEmind application, sequential information generated during medical visits and static information of each patient. Our goal with this dataset is to predict the suicidal ideation value that each patient will report next. In order to model both datasets, we have developed a set of predictive Machine Learning models based on Neural Networks capable of integrating multiple sequences of data withthe background information of each patient. We compare the performance achieved by these approaches with the ones obtained with classical ML algorithms. For the task of predicting the next events that will be observed in the nephrology dataset, we obtained the best performance with a Feedforward Neural Network containing a representation layer. On the other hand, for the tasks of endpoint prediction in nephrology patients and the task of suicidal ideation prediction, we obtained the best performance with a model that combines a Feedforward Neural Network with one or multiple Recurrent Neural Networks (RNNs) using Gated Recurrent Units. We hypothesize that this kind of models that include RNNs provide the best performance when the dataset contains long-term dependencies. To our knowledge, our work is the first one that develops these kind of deep networks that combine both static and several sources of dynamic information. These models can be useful in many other medical datasets and even in datasets within other domains. We show some examples where our approach is successfully applied to non-medical datasets that also present multiple variables evolving in time. Besides, we installed the endpoints prediction model as a standalone system in the Charit ́e hospital in Berlin. For this purpose, we developed a web based user interface that the physicians can use, and an API interface that can be used to connect our predictive system with other IT systems in the hospital. These systems can be seen as a recommender system, however they do not necessarily generate valid prescriptions. For example, for certain patient, a system can predict very high probabilities for all antibiotics in the dataset. Obviously, this patient should not take all antibiotics, but only one of them. Therefore, we need a human decision maker on top of our recommender system. In order to model this decision process, we used an architecture based on a Generative Adversarial Network (GAN). GANs are systems based on Neural Networks that make better generative models than regular Neural Networks. Thus we trained one GAN that works on top of a regular Neural Network and show how the quality of the prescriptions gets improved. We run this experiment with a synthetic dataset that we created for this purpose. The architectures that we developed, are specially designed for modelling medical data, but they can be also useful in other use cases. We run experiments showing how we train them for modelling the readings of a sensor network and also to train a movie recommendation engine

A step towards Advancing Digital Phenotyping In Mental Healthcare

Smartphones and wrist-wearable devices have infiltrated our lives in recent years. According to published statistics, nearly 84% of the world’s population owns a smartphone, and almost 10% own a wearable device today (2022). These devices continuously generate various data sources from multiple sensors and apps, creating our digital phenotypes. This opens new research opportunities, particularly in mental health care, which has previously relied almost exclusively on self-reports of mental health symptoms. Unobtrusive monitoring using patients’ devices may result in clinically valuable markers that can improve diagnostic processes, tailor treatment choices, provide continuous insights into their condition for actionable outcomes, such as early signs of relapse, and develop new intervention models. However, these data sources must be translated into meaningful, actionable features related to mental health to achieve their full potential. In the mental health field, there is a great need and much to be gained from defining a way to continuously assess the evolution of patients’ mental states, ideally in their everyday environment, to support the monitoring and treatments by health care providers. A smartphone-based approach may be valuable in gathering long-term objective data, aside from the usually used self-ratings, to predict clinical state changes and investigate causal inferences about state changes in patients (e.g., those with affective disorders). Being objective does not imply that passive data collection is also perfect. It has several challenges: some sensors generate vast volumes of data, and others cause significant battery drain. Furthermore, the analysis of raw passive data is complicated, and collecting certain types of data may interfere with the phenotype of interest. Nonetheless, machine learning is predisposed to address these matters and advance psychiatry’s era of personalised medicine. This work aimed to advance the research efforts on mobile and wearable sensors for mental health monitoring. We applied supervised and unsupervised machine learning methods to model and understand mental disease evolution based on the digital phenotype of patients and clinician assessments at the follow-up visits, which provide ground truths. We needed to cope with regularly and irregularly sampled, high-dimensional, and heterogeneous time series data susceptible to distortion and missingness. Hence, the developed methods must be robust to these limitations and handle missing data properly. Throughout the various projects presented here, we used probabilistic latent variable models for data imputation and feature extraction, namely, mixture models (MM) and hidden Markov models (HMM). These unsupervised models can learn even in the presence of missing data by marginalising the missing values in the function of the present observations. Once the generative models are trained on the data set with missing values, they can be used to generate samples for imputation. First, the most probable component/state has to be found for each sample. Then, sampling from the most probable distribution yields valid and robust parameter estimates and explicit imputed values for variables that can be analysed as outcomes or predictors. The imputation process can be repeated several times, creating multiple datasets, thereby accounting for the uncertainty in the imputed values and implicitly augmenting the data. Moreover, they are robust to moderate deviations of the observed data from the assumed underlying distribution and provide accurate estimates even when missingness is high. Depending on the properties of the data at hand, we employed feature extraction methods combined with classical machine learning algorithms or deep learning-based techniques for temporal modelling to predict various mental health outcomes - emotional state, World Health Organisation Disability Assessment Schedule (WHODAS 2.0) functionality scores and Generalised Anxiety Disorder-7 (GAD-7) scores, of psychiatric outpatients. We mainly focused on one-size-fits-all models, as the labelled sample size per patient was limited; however, in the mood prediction case, it was possible to apply personalised models. Integrating machines and algorithms into the clinical workflow require interpretability to increase acceptance. Therefore, we also analysed feature importance by computing Shapley additive explanations (SHAP) values. SHAP values provide an overview of essential features in the machine learning models by designating the weight of predictability of each feature positively or negatively to the target variable. The provided solutions, as such, are proof of concept, which require further clinical validation to be deployable in the clinical workflow. Still, the results are promising and lay some foundations for future research and collaboration among clinicians, patients, and computer scientists. They set the paths to advance future research prospects in technology-based mental healthcare.En los últimos años, los smartphones y los dispositivos y pulseras inteligentes, comúnmente conocidos como wearables, se han infiltrado en nuestras vidas. Según las estadísticas publicadas a día de hoy (2022), cerca del 84% de la población tiene un smartphone y aproximadamente un 10% también posee un wearable. Estos dispositivos generan datos de forma continua en base a distintos sensores y aplicaciones, creando así nuestro fenotipo digital. Estos datos abren nuevas vías de investigación, particularmente en el área de salud mental, dónde las fuentes de datos han sido casi exclusivamente autoevaluaciones de síntomas de salud mental. Monitorizar de forma no intrusiva a los pacientes mediante sus dispositivos puede dar lugar a marcadores valiosos en aplicación clínica. Esto permite mejorar los procesos de diagnóstico, adaptar tratamientos, e incluso proporcionar información continua sobre el estado de los pacientes, como signos tempranos de recaída, y hasta desarrollar nuevos modelos de intervención. Aun así, estos datos en crudo han de ser traducidos a datos interpretables relacionados con la salud mental para conseguir un máximo rendimiento de los mismos. En salud mental existe una gran necesidad, y además hay mucho que ganar, de definir cómo evaluar de forma continuada la evolución del estado mental de los pacientes en su entorno cotidiano para ayudar en el tratamiento y seguimiento de los mismos por parte de los profesionales sanitarios. En este ámbito, un enfoque basado en datos recopilados desde sus smartphones puede ser valioso para recoger datos objetivos a largo plazo al mismo tiempo que se acompaña de las autoevaluaciones utilizadas habitualmente. La combinación de ambos tipos de datos puede ayudar a predecir los cambios en el estado clínico de estos pacientes e investigar las relaciones causales sobre estos cambios (por ejemplo, en aquellos que padecen trastornos afectivos). Aunque la recogida de datos de forma pasiva tiene la ventaja de ser objetiva, también implica varios retos. Por un lado, ciertos sensores generan grandes volúmenes de datos, provocando un importante consumo de batería. Además, el análisis de los datos pasivos en crudo es complicado, y la recogida de ciertos tipos de datos puede interferir con el fenotipo que se quiera analizar. No obstante, el machine learning o aprendizaje automático, está predispuesto a resolver estas cuestiones y aportar avances en la medicina personalizada aplicada a psiquiatría. Esta tesis tiene como objetivo avanzar en la investigación de los datos recogidos por sensores de smartphones y wearables para la monitorización en salud mental. Para ello, aplicamos métodos de aprendizaje automático supervisado y no supervisado para modelar y comprender la evolución de las enfermedades mentales basándonos en el fenotipo digital de los pacientes. Estos resultados se comparan con las evaluaciones de los médicos en las visitas de seguimiento, que proporcionan las etiquetas reales. Para aplicar estos métodos hemos lidiado con datos provenientes de series temporales con alta dimensionalidad, muestreados de forma regular e irregular, heterogéneos y, además, susceptibles a presentar patrones de datos perdidos y/o distorsionados. Por lo tanto, los métodos desarrollados deben ser resistentes a estas limitaciones y manejar adecuadamente los datos perdidos. A lo largo de los distintos proyectos presentados en este trabajo, hemos utilizado modelos probabilísticos de variables latentes para la imputación de datos y la extracción de características, como por ejemplo, Mixture Models (MM) y hidden Markov Models (HMM). Estos modelos no supervisados pueden aprender incluso en presencia de datos perdidos, marginalizando estos valores en función de las datos que sí han sido observados. Una vez entrenados los modelos generativos en el conjunto de datos con valores perdidos, pueden utilizarse para imputar dichos valores generando muestras. En primer lugar, hay que encontrar el componente/estado más probable para cada muestra. Luego, se muestrea de la distirbución más probable resultando en estimaciones de parámetros robustos y válidos. Además, genera imputaciones explícitas que pueden ser tratadas como resultados. Este proceso de imputación puede repetirse varias veces, creando múltiples conjuntos de datos, con lo que se tiene en cuenta la incertidumbre de los valores imputados y aumentándose así, implícitamente, los datos. Además, estas imputaciones son resistentes a desviaciones que puedan existir en los datos observados con respecto a la distribución subyacente asumida y proporcionan estimaciones precisas incluso cuando la falta de datos es elevada. Dependiendo de las propiedades de los datos en cuestión, hemos usado métodos de extracción de características combinados con algoritmos clásicos de aprendizaje automático o técnicas basadas en deep learning o aprendizaje profundo para el modelado temporal. La finalidad de ambas opciones es ser capaces de predecir varios resultados de salud mental/estado emocional, como la puntuación sobre el World Health Organisation Disability Assessment Schedule (WHODAS 2.0), o las puntuaciones del generalised anxiety disorder-7 (GAD-7) de pacientes psiquiátricos ambulatorios. Nos centramos principalmente en modelos generalizados, es decir, no personalizados para cada paciente sino explicativos para la mayoría, ya que el tamaño de muestras etiquetada por paciente es limitado; sin embargo, en el caso de la predicción del estado de ánimo, puidmos aplicar modelos personalizados. Para que la integración de las máquinas y algoritmos dentro del flujo de trabajo clínico sea aceptada, se requiere que los resultados sean interpretables. Por lo tanto, en este trabajo también analizamos la importancia de las características sacadas por cada algoritmo en base a los valores de las explicaciones aditivas de Shapley (SHAP). Estos valores proporcionan una visión general de las características esenciales en los modelos de aprendizaje automático designando el peso, positivo o negativo, de cada característica en su predictibilidad sobre la variable objetivo. Las soluciones aportadas en esta tesis, como tales, son pruebas de concepto, que requieren una mayor validación clínica para poder ser desplegadas en el flujo de trabajo clínico. Aun así, los resultados son prometedores y sientan base para futuras investigaciones y colaboraciones entre clínicos, pacientes y científicos de datos. Éstas establecen las guías para avanzar en las perspectivas de investigación futuras en la atención sanitaria mental basada en la tecnología.Programa de Doctorado en Multimedia y Comunicaciones por la Universidad Carlos III de Madrid y la Universidad Rey Juan CarlosPresidente: David Ramírez García.- Secretario: Alfredo Nazábal Rentería.- Vocal: María Luisa Barrigón Estéve