Multiomics and digital monitoring during lifestyle changes reveal independent dimensions of human biology and health.

We explored opportunities for personalized and predictive health care by collecting serial clinical measurements, health surveys, genomics, proteomics, autoantibodies, metabolomics, and gut microbiome data from 96 individuals who participated in a data-driven health coaching program over a 16-month period with continuous digital monitoring of activity and sleep. We generated a resource of >20,000 biological samples from this study and a compendium of >53 million primary data points for 558,032 distinct features. Multiomics factor analysis revealed distinct and independent molecular factors linked to obesity, diabetes, liver function, cardiovascular disease, inflammation, immunity, exercise, diet, and hormonal effects. For example, ethinyl estradiol, a common oral contraceptive, produced characteristic molecular and physiological effects, including increased levels of inflammation and impact on thyroid, cortisol levels, and pulse, that were distinct from other sources of variability observed in our study. In total, this work illustrates the value of combining deep molecular and digital monitoring of human health. A record of this paper's transparent peer review process is included in the supplemental information.

Serum Biomarkers of Allergic Contact Dermatitis: A Pilot Study.

BACKGROUND: Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by repeated skin exposure to contact allergens. The goal of this pilot study was to identify inflammatory proteins which can serve as biomarkers for ACD. METHODS: We measured levels of 102 cytokines, chemokines, and growth factors in the sera of 16 ACD patients during acute and remission phases, and 16 healthy volunteers. RESULTS: Serum levels of adiponectin, chemokine (C-C motif) ligand 5 (CCL5), C-reactive protein (CRP), chitinase 3-like 1 (CHI3L1), complement factor D (CFD), endoglin, lipocalin-2, osteopontin, retinol-binding protein 4 (RBP4), and platelet factor 4 (PF4) were significantly higher, whereas levels of trefoil factor 3 (TFF3) were significantly lower, in ACD patients than in healthy controls. In ACD patients, serum levels of CCL5 were elevated, whereas levels of TFF3, soluble intercellular adhesion molecule-1 (sICAM-1), and platelet-derived growth factor (PDGF)-AB/BB were found to be lower during the remission phase of the disease. CONCLUSIONS: Serum levels of adiponectin, CCL5, CRP, CHI3L1, CFD, endoglin, lipocalin-2, osteopontin, RBP4, PF4, and TFF3 might be exploited as biomarkers for ACD, whereas levels of CCL5, TFF3, sICAM-1, and PDGF-AB/BB might be exploited for evaluation of disease progression and efficacy of ACD treatment.

The Finnish disease heritage database (FinDis) update-a database for the genes mutated in the Finnish disease heritage brought to the next-generation sequencing era.

The Finnish Disease Heritage Database (FinDis) (http://findis.org) was originally published in 2004 as a centralized information resource for rare monogenic diseases enriched in the Finnish population. The FinDis database originally contained 405 causative variants for 30 diseases. At the time, the FinDis database was a comprehensive collection of data, but since 1994, a large amount of new information has emerged, making the necessity to update the database evident. We collected information and updated the database to contain genes and causative variants for 35 diseases, including six more genes and more than 1,400 additional disease-causing variants. Information for causative variants for each gene is collected under the LOVD 3.0 platform, enabling easy updating. The FinDis portal provides a centralized resource and user interface to link information on each disease and gene with variant data in the LOVD 3.0 platform. The software written to achieve this has been open-sourced and made available on GitHub (http://github.com/findis-db), allowing biomedical institutions in other countries to present their national data in a similar way, and to both contribute to, and benefit from, standardized variation data. The updated FinDis portal provides a unique resource to assist patient diagnosis, research, and the development of new cures.

VarioML framework for comprehensive variation data representation and exchange.

BACKGROUND: Sharing of data about variation and the associated phenotypes is a critical need, yet variant information can be arbitrarily complex, making a single standard vocabulary elusive and re-formatting difficult. Complex standards have proven too time-consuming to implement. RESULTS: The GEN2PHEN project addressed these difficulties by developing a comprehensive data model for capturing biomedical observations, Observ-OM, and building the VarioML format around it. VarioML pairs a simplified open specification for describing variants, with a toolkit for adapting the specification into one's own research workflow. Straightforward variant data can be captured, federated, and exchanged with no overhead; more complex data can be described, without loss of compatibility. The open specification enables push-button submission to gene variant databases (LSDBs) e.g., the Leiden Open Variation Database, using the Cafe Variome data publishing service, while VarioML bidirectionally transforms data between XML and web-application code formats, opening up new possibilities for open source web applications building on shared data. A Java implementation toolkit makes VarioML easily integrated into biomedical applications. VarioML is designed primarily for LSDB data submission and transfer scenarios, but can also be used as a standard variation data format for JSON and XML document databases and user interface components. CONCLUSIONS: VarioML is a set of tools and practices improving the availability, quality, and comprehensibility of human variation information. It enables researchers, diagnostic laboratories, and clinics to share that information with ease, clarity, and without ambiguity.

Observ-OM and Observ-TAB: Universal syntax solutions for the integration, search, and exchange of phenotype and genotype information.

Genetic and epidemiological research increasingly employs large collections of phenotypic and molecular observation data from high quality human and model organism samples. Standardization efforts have produced a few simple formats for exchange of these various data, but a lightweight and convenient data representation scheme for all data modalities does not exist, hindering successful data integration, such as assignment of mouse models to orphan diseases and phenotypic clustering for pathways. We report a unified system to integrate and compare observation data across experimental projects, disease databases, and clinical biobanks. The core object model (Observ-OM) comprises only four basic concepts to represent any kind of observation: Targets, Features, Protocols (and their Applications), and Values. An easy-to-use file format (Observ-TAB) employs Excel to represent individual and aggregate data in straightforward spreadsheets. The systems have been tested successfully on human biobank, genome-wide association studies, quantitative trait loci, model organism, and patient registry data using the MOLGENIS platform to quickly setup custom data portals. Our system will dramatically lower the barrier for future data sharing and facilitate integrated search across panels and species. All models, formats, documentation, and software are available for free and open source (LGPLv3) at http://www.observ-om.org.