Genetic fine-mapping from summary data using a nonlocal prior improves the detection of multiple causal variants.

MOTIVATION: Genome-wide association studies (GWAS) have been successful in identifying genomic loci associated with complex traits. Genetic fine-mapping aims to detect independent causal variants from the GWAS-identified loci, adjusting for linkage disequilibrium patterns. RESULTS: We present "FiniMOM" (fine-mapping using a product inverse-moment prior), a novel Bayesian fine-mapping method for summarized genetic associations. For causal effects, the method uses a nonlocal inverse-moment prior, which is a natural prior distribution to model non-null effects in finite samples. A beta-binomial prior is set for the number of causal variants, with a parameterization that can be used to control for potential misspecifications in the linkage disequilibrium reference. The results of simulations studies aimed to mimic a typical GWAS on circulating protein levels show improved credible set coverage and power of the proposed method over current state-of-the-art fine-mapping method SuSiE, especially in the case of multiple causal variants within a locus. AVAILABILITY AND IMPLEMENTATION: https://vkarhune.github.io/finimom/.

EDISON: An Edge-Native Method and Architecture for Distributed Interpolation.

Spatio-temporal interpolation provides estimates of observations in unobserved locations and time slots. In smart cities, interpolation helps to provide a fine-grained contextual and situational understanding of the urban environment, in terms of both short-term (e.g., weather, air quality, traffic) or long term (e.g., crime, demographics) spatio-temporal phenomena. Various initiatives improve spatio-temporal interpolation results by including additional data sources such as vehicle-fitted sensors, mobile phones, or micro weather stations of, for example, smart homes. However, the underlying computing paradigm in such initiatives is predominantly centralized, with all data collected and analyzed in the cloud. This solution is not scalable, as when the spatial and temporal density of sensor data grows, the required transmission bandwidth and computational capacity become unfeasible. To address the scaling problem, we propose EDISON: algorithms for distributed learning and inference, and an edge-native architecture for distributing spatio-temporal interpolation models, their computations, and the observed data vertically and horizontally between device, edge and cloud layers. We demonstrate EDISON functionality in a controlled, simulated spatio-temporal setup with 1 M artificial data points. While the main motivation of EDISON is the distribution of the heavy computations, the results show that EDISON also provides an improvement over alternative approaches, reaching at best a 10% smaller RMSE than a global interpolation and 6% smaller RMSE than a baseline distributed approach.

A Novel Approach for Continuous Health Status Monitoring and Automatic Detection of Infection Incidences in People With Type 1 Diabetes Using Machine Learning Algorithms (Part 2): A Personalized Digital Infectious Disease Detection Mechanism.

BACKGROUND: Semisupervised and unsupervised anomaly detection methods have been widely used in various applications to detect anomalous objects from a given data set. Specifically, these methods are popular in the medical domain because of their suitability for applications where there is a lack of a sufficient data set for the other classes. Infection incidence often brings prolonged hyperglycemia and frequent insulin injections in people with type 1 diabetes, which are significant anomalies. Despite these potentials, there have been very few studies that focused on detecting infection incidences in individuals with type 1 diabetes using a dedicated personalized health model. OBJECTIVE: This study aims to develop a personalized health model that can automatically detect the incidence of infection in people with type 1 diabetes using blood glucose levels and insulin-to-carbohydrate ratio as input variables. The model is expected to detect deviations from the norm because of infection incidences considering elevated blood glucose levels coupled with unusual changes in the insulin-to-carbohydrate ratio. METHODS: Three groups of one-class classifiers were trained on target data sets (regular days) and tested on a data set containing both the target and the nontarget (infection days). For comparison, two unsupervised models were also tested. The data set consists of high-precision self-recorded data collected from three real subjects with type 1 diabetes incorporating blood glucose, insulin, diet, and events of infection. The models were evaluated on two groups of data: raw and filtered data and compared based on their performance, computational time, and number of samples required. RESULTS: The one-class classifiers achieved excellent performance. In comparison, the unsupervised models suffered from performance degradation mainly because of the atypical nature of the data. Among the one-class classifiers, the boundary and domain-based method produced a better description of the data. Regarding the computational time, nearest neighbor, support vector data description, and self-organizing map took considerable training time, which typically increased as the sample size increased, and only local outlier factor and connectivity-based outlier factor took considerable testing time. CONCLUSIONS: We demonstrated the applicability of one-class classifiers and unsupervised models for the detection of infection incidence in people with type 1 diabetes. In this patient group, detecting infection can provide an opportunity to devise tailored services and also to detect potential public health threats. The proposed approaches achieved excellent performance; in particular, the boundary and domain-based method performed better. Among the respective groups, particular models such as one-class support vector machine, K-nearest neighbor, and K-means achieved excellent performance in all the sample sizes and infection cases. Overall, we foresee that the results could encourage researchers to examine beyond the presented features into other additional features of the self-recorded data, for example, continuous glucose monitoring features and physical activity data, on a large scale.

Toward Detecting Infection Incidence in People With Type 1 Diabetes Using Self-Recorded Data (Part 1): A Novel Framework for a Personalized Digital Infectious Disease Detection System.

BACKGROUND: Type 1 diabetes is a chronic condition of blood glucose metabolic disorder caused by a lack of insulin secretion from pancreas cells. In people with type 1 diabetes, hyperglycemia often occurs upon infection incidences. Despite the fact that patients increasingly gather data about themselves, there are no solid findings that uncover the effect of infection incidences on key parameters of blood glucose dynamics to support the effort toward developing a digital infectious disease detection system. OBJECTIVE: The study aims to retrospectively analyze the effect of infection incidence and pinpoint optimal parameters that can effectively be used as input variables for developing an infection detection algorithm and to provide a general framework regarding how a digital infectious disease detection system can be designed and developed using self-recorded data from people with type 1 diabetes as a secondary source of information. METHODS: We retrospectively analyzed high precision self-recorded data of 10 patient-years captured within the longitudinal records of three people with type 1 diabetes. Obtaining such a rich and large data set from a large number of participants is extremely expensive and difficult to acquire, if not impossible. The data set incorporates blood glucose, insulin, carbohydrate, and self-reported events of infections. We investigated the temporal evolution and probability distribution of the key blood glucose parameters within a specified timeframe (weekly, daily, and hourly). RESULTS: Our analysis demonstrated that upon infection incidence, there is a dramatic shift in the operating point of the individual blood glucose dynamics in all the timeframes (weekly, daily, and hourly), which clearly violates the usual norm of blood glucose dynamics. During regular or normal situations, higher insulin and reduced carbohydrate intake usually results in lower blood glucose levels. However, in all infection cases as opposed to the regular or normal days, blood glucose levels were elevated for a prolonged period despite higher insulin and reduced carbohydrates intake. For instance, compared with the preinfection and postinfection weeks, on average, blood glucose levels were elevated by 6.1% and 16%, insulin (bolus) was increased by 42% and 39.3%, and carbohydrate consumption was reduced by 19% and 28.1%, respectively. CONCLUSIONS: We presented the effect of infection incidence on key parameters of blood glucose dynamics along with the necessary framework to exploit the information for realizing a digital infectious disease detection system. The results demonstrated that compared with regular or normal days, infection incidence substantially alters the norm of blood glucose dynamics, which are quite significant changes that could possibly be detected through personalized modeling, for example, prediction models and anomaly detection algorithms. Generally, we foresee that these findings can benefit the efforts toward building next generation digital infectious disease detection systems and provoke further thoughts in this challenging field.