Deep Learning Applications for Biomedical Data and Natural Language Processing

The human brain can be seen as an ensemble of interconnected neurons, more or less specialized to solve different cognitive and motor tasks. In computer science, the term deep learning is often applied to signify sets of interconnected nodes, where deep means that they have several computational layers. Development of deep learning is essentially a quest to mimic how the human brain, at least partially, operates.In this thesis, I will use machine learning techniques to tackle two different domain of problems. The first is a problem in natural language processing. We improved classification of relations within images, using text associated with the pictures. The second domain is regarding heart transplant. We created models for pre- and post-transplant survival and simulated a whole transplantation queue, to be able to asses the impact of different allocation policies. We used deep learning models to solve these problems.As introduction to these problems, I will present the basic concepts of machine learning, how to represent data, how to evaluate prediction results, and how to create different models to predict values from data. Following that, I will also introduce the field of heart transplant and some information about simulation

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 systematic review of the prediction of hospital length of stay:Towards a unified framework

Hospital length of stay of patients is a crucial factor for the effective planning and management of hospital resources. There is considerable interest in predicting the LoS of patients in order to improve patient care, control hospital costs and increase service efficiency. This paper presents an extensive review of the literature, examining the approaches employed for the prediction of LoS in terms of their merits and shortcomings. In order to address some of these problems, a unified framework is proposed to better generalise the approaches that are being used to predict length of stay. This includes the investigation of the types of routinely collected data used in the problem as well as recommendations to ensure robust and meaningful knowledge modelling. This unified common framework enables the direct comparison of results between length of stay prediction approaches and will ensure that such approaches can be used across several hospital environments. A literature search was conducted in PubMed, Google Scholar and Web of Science from 1970 until 2019 to identify LoS surveys which review the literature. 32 Surveys were identified, from these 32 surveys, 220 papers were manually identified to be relevant to LoS prediction. After removing duplicates, and exploring the reference list of studies included for review, 93 studies remained. Despite the continuing efforts to predict and reduce the LoS of patients, current research in this domain remains ad-hoc; as such, the model tuning and data preprocessing steps are too specific and result in a large proportion of the current prediction mechanisms being restricted to the hospital that they were employed in. Adopting a unified framework for the prediction of LoS could yield a more reliable estimate of the LoS as a unified framework enables the direct comparison of length of stay methods. Additional research is also required to explore novel methods such as fuzzy systems which could build upon the success of current models as well as further exploration of black-box approaches and model interpretability

AI models and the future of genomic research and medicine: True sons of knowledge? Artificial intelligence needs to be integrated with causal conceptions in biomedicine to harness its societal benefits for the field

The increasing availability of large-scale, complex data has made research into how human genomes determine physiology in health and disease, as well as its application to drug development and medicine, an attractive field for artificial intelligence (AI) approaches. Looking at recent developments, we explore how such approaches interconnect and may conflict with needs for and notions of causal knowledge in molecular genetics and genomic medicine. We provide reasons to suggest that—while capable of generating predictive knowledge at unprecedented pace and scale—if and how these approaches will be integrated with prevailing causal concepts will not only determine the future of scientific understanding and self-conceptions in these fields. But these questions will also be key to develop differentiated policies, such as for education and regulation, in order to harness societal benefits of AI for genomic research and medicine

Big Data and the Precision Medicine Revolution

The big data revolution is making vast amounts of information available in all sectors of the economy including health care. One important type of data that is particularly relevant to medicine is observational data from actual practice. In comparison to experimental data from clinical studies, observational data offers much larger sample sizes and much broader coverage of patient variables. Properly combining observational data with experimental data can facilitate precision medicine by enabling detection of heterogeneity in patient responses to treatments and tailoring of health care to the specific needs of individuals. However, because it is high-dimensional and uncontrolled, observational data presents unique methodological challenges. The modeling and analysis tools of the production and operations management field are well-suited to these challenges and hence POM scholars are critical to the realization of precision medicine with its many benefits to society.https://deepblue.lib.umich.edu/bitstream/2027.42/145441/1/1386_Hopp.pd

Explainable AI for clinical risk prediction: a survey of concepts, methods, and modalities

Recent advancements in AI applications to healthcare have shown incredible promise in surpassing human performance in diagnosis and disease prognosis. With the increasing complexity of AI models, however, concerns regarding their opacity, potential biases, and the need for interpretability. To ensure trust and reliability in AI systems, especially in clinical risk prediction models, explainability becomes crucial. Explainability is usually referred to as an AI system's ability to provide a robust interpretation of its decision-making logic or the decisions themselves to human stakeholders. In clinical risk prediction, other aspects of explainability like fairness, bias, trust, and transparency also represent important concepts beyond just interpretability. In this review, we address the relationship between these concepts as they are often used together or interchangeably. This review also discusses recent progress in developing explainable models for clinical risk prediction, highlighting the importance of quantitative and clinical evaluation and validation across multiple common modalities in clinical practice. It emphasizes the need for external validation and the combination of diverse interpretability methods to enhance trust and fairness. Adopting rigorous testing, such as using synthetic datasets with known generative factors, can further improve the reliability of explainability methods. Open access and code-sharing resources are essential for transparency and reproducibility, enabling the growth and trustworthiness of explainable research. While challenges exist, an end-to-end approach to explainability in clinical risk prediction, incorporating stakeholders from clinicians to developers, is essential for success

Splitting Deceased Donor Livers to Double the Transplant Benefits: Addressing the Legal, Ethical, and Practical Challenges

Liver transplantation is different from transplanting other solid organs because some recipients can achieve good long-term outcomes with only half of a donor’s liver (or less). This means that some deceased donor livers can be split, saving two lives instead of one. However, although more than 10 percent of cadaveric livers meet the criteria for splitting, only about 1.5 percent are actually split in the United States. This article identifies a set of ethical, legal, and logistical challenges to a more extensive use of split liver transplantation (SLT) within existing legal frameworks. We then discuss how each of these challenges can be overcome with a set of realistic clarifications and changes to the current liver transplant architecture. Three guiding values shape liver allocation policy in the United States: maximizing expected outcomes, ensuring broad access, and prioritizing the sickest patients. While the last value is in tension with SLT (because the sickest patients often need a whole liver), we maintain that greater adoption of SLT is consistent with this normative balance. In addition, the distribution infrastructure is not designed to facilitate splitting. When a surgical team is offered a liver for a specific patient, they feel duty-bound to give that specific patient the whole organ. Further discouraging SLT, performance metrics, including those used to determine a transplant program’s eligibility for Medicare and Medicaid funding, focus on surgical outcomes rather than waitlist mortality. Our preferred remedies entail clarifying the informed consent requirements for SLT, using a national clearinghouse to identify livers that are prime candidates for splitting, offering these livers to qualifying programs for SLT only, and establishing a separate regulatory reporting and outcomes evaluation pathway for SLT. Together, these reforms, many of which have precedents in the transplant field, will support the expansion of SLT in carefully controlled conditions and save more lives

Ethical Framework for Harnessing the Power of AI in Healthcare and Beyond

In the past decade, the deployment of deep learning (Artificial Intelligence (AI)) methods has become pervasive across a spectrum of real-world applications, often in safety-critical contexts. This comprehensive research article rigorously investigates the ethical dimensions intricately linked to the rapid evolution of AI technologies, with a particular focus on the healthcare domain. Delving deeply, it explores a multitude of facets including transparency, adept data management, human oversight, educational imperatives, and international collaboration within the realm of AI advancement. Central to this article is the proposition of a conscientious AI framework, meticulously crafted to accentuate values of transparency, equity, answerability, and a human-centric orientation. The second contribution of the article is the in-depth and thorough discussion of the limitations inherent to AI systems. It astutely identifies potential biases and the intricate challenges of navigating multifaceted contexts. Lastly, the article unequivocally accentuates the pressing need for globally standardized AI ethics principles and frameworks. Simultaneously, it aptly illustrates the adaptability of the ethical framework proposed herein, positioned skillfully to surmount emergent challenges