Using uncertain data from body-worn sensors to gain insight into type 1 diabetes.

The amount of observational data available for research is growing rapidly with the rise of electronic health records and patient-generated data. However, these data bring new challenges, as data collected outside controlled environments and generated for purposes other than research may be error-prone, biased, or systematically missing. Analysis of these data requires methods that are robust to such challenges, yet methods for causal inference currently only handle uncertainty at the level of causal relationships - rather than variables or specific observations.

A Digital Ecosystem of Diabetes Data and Technology: Services, Systems, and Tools Enabled by Wearables, Sensors, and Apps.

The management of type 1 diabetes (T1D) ideally involves regimented measurement of various health signals; constant interpretation of diverse kinds of data; and consistent cohesion between patients, caregivers, and health care professionals (HCPs). In the context of myriad factors that influence blood glucose dynamics for each individual patient (eg, medication, activity, diet, stress, sleep quality, hormones, environment), such coordination of self-management and clinical care is a great challenge, amplified by the routine unavailability of many types of data thought to be useful in diabetes decision-making. While much remains to be understood about the physiology of diabetes and blood glucose dynamics at the level of the individual, recent and emerging medical and consumer technologies are helping the diabetes community to take great strides toward truly personalized, real-time, data-driven management of this chronic disease.

Combining Fourier and lagged k-nearest neighbor imputation for biomedical time series data.

Most clinical and biomedical data contain missing values. A patient's record may be split across multiple institutions, devices may fail, and sensors may not be worn at all times. While these missing values are often ignored, this can lead to bias and error when the data are mined.

Nocturnal continuous glucose and sleep stage data in adults with type 1 diabetes in real-world conditions.

Background: Sleep plays an important role in health, and poor sleep is associated with negative impacts on diabetes management, but few studies have objectively evaluated sleep in adults with type 1 diabetes mellitus (T1DM). Nocturnal glycemia and sleep characteristics in T1DM were evaluated using body-worn sensors in real-world conditions.

Methods: Analyses were performed on data collected by the Diabetes Management Integrated Technology Research Initiative pilot study of 17 T1DM subjects: 10 male, 7 female; age 19-61 years; T1DM duration 14.

iDASH: integrating data for analysis, anonymization, and sharing.

iDASH (integrating data for analysis, anonymization, and sharing) is the newest National Center for Biomedical Computing funded by the NIH. It focuses on algorithms and tools for sharing data in a privacy-preserving manner. Foundational privacy technology research performed within iDASH is coupled with innovative engineering for collaborative tool development and data-sharing capabilities in a private Health Insurance Portability and Accountability Act (HIPAA)-certified cloud.

9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response.

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the 9p21 gene desert associated with coronary artery disease (CAD) and type 2 diabetes. Despite evidence for a role of the associated interval in neighbouring gene regulation, the biological underpinnings of these genetic associations with CAD or type 2 diabetes have not yet been explained. Here we identify 33 enhancers in 9p21; the interval is the second densest gene desert for predicted enhancers and six times denser than the whole genome (P < 6.

Finding distal regulatory elements in the human genome.

Transcriptional regulation of human genes depends not only on promoters and nearby cis-regulatory elements, but also on distal regulatory elements such as enhancers, insulators, locus control regions, and silencing elements, which are often located far away from the genes they control. Our knowledge of human distal regulatory elements is very limited, but the last several years have seen rapid progress in the development of strategies to identify these long-range regulatory sequences throughout the human genome. Here, we review these advances, focusing on two important classes of distal regulatory sequences-enhancers and insulators.

Histone modifications at human enhancers reflect global cell-type-specific gene expression.

The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome.

Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome.

Eukaryotic gene transcription is accompanied by acetylation and methylation of nucleosomes near promoters, but the locations and roles of histone modifications elsewhere in the genome remain unclear. We determined the chromatin modification states in high resolution along 30 Mb of the human genome and found that active promoters are marked by trimethylation of Lys4 of histone H3 (H3K4), whereas enhancers are marked by monomethylation, but not trimethylation, of H3K4. We developed computational algorithms using these distinct chromatin signatures to identify new regulatory elements, predicting over 200 promoters and 400 enhancers within the 30-Mb region.