Prospect patents, data markets, and the commons in data-driven medicine : openness and the political economy of intellectual property rights

Scholars who point to political influences and the regulatory function of patent courts in the USA have long questioned the courts’ subjective interpretation of what ‘things’ can be claimed as inventions. The present article sheds light on a different but related facet: the role of the courts in regulating knowledge production. I argue that the recent cases decided by the US Supreme Court and the Federal Circuit, which made diagnostics and software very difficult to patent and which attracted criticism for a wealth of different reasons, are fine case studies of the current debate over the proper role of the state in regulating the marketplace and knowledge production in the emerging information economy. The article explains that these patents are prospect patents that may be used by a monopolist to collect data that everybody else needs in order to compete effectively. As such, they raise familiar concerns about failure of coordination emerging as a result of a monopolist controlling a resource such as datasets that others need and cannot replicate. In effect, the courts regulated the market, primarily focusing on ensuring the free flow of data in the emerging marketplace very much in the spirit of the ‘free the data’ language in various policy initiatives, yet at the same time with an eye to boost downstream innovation. In doing so, these decisions essentially endorse practices of personal information processing which constitute a new type of public domain: a source of raw materials which are there for the taking and which have become most important inputs to commercial activity. From this vantage point of view, the legal interpretation of the private and the shared legitimizes a model of data extraction from individuals, the raw material of information capitalism, that will fuel the next generation of data-intensive therapeutics in the field of data-driven medicine

Data Mining in Large-Scale Clinical Visit Data for Rett Syndrome Patients

Rett syndrome (RTT) is a rare neurological disorder that predominantly affects girls. Research on RTT has mostly centered around gene mutations and possibility of cure using gene therapy. In this thesis we perform the first large scale systematic study of RTT patient records. The thesis has two major goals. One is to identify behavioral groups and the other is to study the association of medications and behavior or conditions. To achieve the first goal we apply standard clustering techniques like non-negative matrix factorization and k-means. We identify behavioral groups which could be used by clinicians for formulating better treatments. For the second goal we start with the most popular existing technique, disproportionality analysis, and make necessary adaptations for our data set. We then generalize this method and suggest an alternate approach which efficiently answers which medication caused the most change in a behavior. We test both approaches and show that the medications shown to decrease seizures the most are indeed those prescribed for the same. Using this as a tool, clinicians can identify possible side effects of medications

Knowledge-based Biomedical Data Science 2019

Knowledge-based biomedical data science (KBDS) involves the design and implementation of computer systems that act as if they knew about biomedicine. Such systems depend on formally represented knowledge in computer systems, often in the form of knowledge graphs. Here we survey the progress in the last year in systems that use formally represented knowledge to address data science problems in both clinical and biological domains, as well as on approaches for creating knowledge graphs. Major themes include the relationships between knowledge graphs and machine learning, the use of natural language processing, and the expansion of knowledge-based approaches to novel domains, such as Chinese Traditional Medicine and biodiversity.Comment: Manuscript 43 pages with 3 tables; Supplemental material 43 pages with 3 table

Simulating drug responses in laboratory test time series with deep generative modeling

Drug effects can be unpredictable and vary widely among patients with environmental, genetic, and clinical factors. Randomized control trials (RCTs) are not sufficient to identify adverse drug reactions (ADRs), and the electronic health record (EHR) along with medical claims have become an important resource for pharmacovigilance. Among all the data collected in hospitals, laboratory tests represent the most documented and reliable data type in the EHR. Laboratory tests are at the core of the clinical decision process and are used for diagnosis, monitoring, screening, and research by physicians. They can be linked to drug effects either directly, with therapeutic drug monitoring (TDM), or indirectly using drug laboratory effects (DLEs) that affect surrogate tests. Unfortunately, very few automated methods use laboratory tests to inform clinical decision making and predict drug effects, partly due to the complexity of these time series that are irregularly sampled, highly dependent on other clinical covariates, and non-stationary. Deep learning, the branch of machine learning that relies on high-capacity artificial neural networks, has known a renewed popularity this past decade and has transformed fields such as computer vision and natural language processing. Deep learning holds the promise of better performances compared to established machine learning models, although with the necessity for larger training datasets due to their higher degrees of freedom. These models are more flexible with multi-modal inputs and can make sense of large amounts of features without extensive engineering. Both qualities make deep learning models ideal candidate for complex, multi-modal, noisy healthcare datasets. With the development of novel deep learning methods such as generative adversarial networks (GANs), there is an unprecedented opportunity to learn how to augment existing clinical dataset with realistic synthetic data and increase predictive performances. Moreover, GANs have the potential to simulate effects of individual covariates such as drug exposures by leveraging the properties of implicit generative models. In this dissertation, I present a body of work that aims at paving the way for next generation laboratory test-based clinical decision support systems powered by deep learning. To this end, I organized my experiments around three building blocks: (1) the evaluation of various deep learning architectures with laboratory test time series and their covariates with a forecasting task; (2) the development of implicit generative models of laboratory test time series using the Wasserstein GAN framework; (3) the inference properties of these models for the simulation of drug effects in laboratory test time series, and their application for data augmentation. Each component has its own evaluation: The forecasting task enabled me to explore the properties and performances of different learning architectures; the Wasserstein GAN models are evaluated with both intrinsic metrics and extrinsic tasks, and I always set baselines to avoid providing results in a "neural-network only" referential. Applied machine learning, and more so with deep learning, is an empirical science. While the datasets used in this dissertation are not publicly available due to patient privacy regulation, I described pre-processing steps, hyper-parameters selection and training processes with reproducibility and transparency in mind. In the specific context of these studies involving laboratory test time series and their clinical covariates, I found that for supervised tasks, machine learning holds up well against deep learning methods. Complex recurrent architectures like long short-term memory (LSTM) do not perform well on these short time series, while convolutional neural networks (CNNs) and multi-layer perceptrons (MLPs) provide the best performances, at the cost of extensive hyper-parameter tuning. Generative adversarial networks, enabled by deep learning models, were able to generate high-fidelity laboratory test time series, and the quality of the generated samples was increased with conditional models using drug exposures as auxiliary information. Interestingly, forecasting models trained on synthetic data exclusively still retain good performances, confirming the potential of GANs in privacy-oriented applications. Finally, conditional GANs demonstrated an ability to interpolate samples from drug exposure combinations not seen during training, opening the way for laboratory test simulation with larger auxiliary information spaces. In specific cases, augmenting real training sets with synthetic data improved performances in the forecasting tasks, and could be extended to other applications where rare cases present a high prediction error

Content Based Image Retrieval (CBIR) in Remote Clinical Diagnosis and Healthcare

Content-Based Image Retrieval (CBIR) locates, retrieves and displays images alike to one given as a query, using a set of features. It demands accessible data in medical archives and from medical equipment, to infer meaning after some processing. A problem similar in some sense to the target image can aid clinicians. CBIR complements text-based retrieval and improves evidence-based diagnosis, administration, teaching, and research in healthcare. It facilitates visual/automatic diagnosis and decision-making in real-time remote consultation/screening, store-and-forward tests, home care assistance and overall patient surveillance. Metrics help comparing visual data and improve diagnostic. Specially designed architectures can benefit from the application scenario. CBIR use calls for file storage standardization, querying procedures, efficient image transmission, realistic databases, global availability, access simplicity, and Internet-based structures. This chapter recommends important and complex aspects required to handle visual content in healthcare.Comment: 28 pages, 6 figures, Book Chapter from "Encyclopedia of E-Health and Telemedicine

Integrative methods for analyzing big data in precision medicine

We provide an overview of recent developments in big data analyses in the context of precision medicine and health informatics. With the advance in technologies capturing molecular and medical data, we entered the area of “Big Data” in biology and medicine. These data offer many opportunities to advance precision medicine. We outline key challenges in precision medicine and present recent advances in data integration-based methods to uncover personalized information from big data produced by various omics studies. We survey recent integrative methods for disease subtyping, biomarkers discovery, and drug repurposing, and list the tools that are available to domain scientists. Given the ever-growing nature of these big data, we highlight key issues that big data integration methods will face