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Biology subjects

Kelly, S. C.

Publications and source records attributed to Kelly, S. C..

3 recordsLinked to original sources

BiomarkerKB: FAIR and Integrated Biomarker Knowledge Connecting Biomolecular and Clinical Data Types

Biomarkers are essential tools for disease detection, risk assessment, therapeutic monitoring, and precision medicine. However, biomarker data are dispersed across heterogeneous resources, inconsistently reported in the literature, and rarely standardized for computational use. This fragmentation limits reproducibility, cross-study integration, and the discovery of novel biomarker and disease relationships. We developed BiomarkerKB, a knowledgebase designed to harmonize and integrate biomarker information under a standardized data model. The model follows the FDA-NIH BEST biomarker definition and captures both core fields (biomarker entity, disease/condition, exposure agent) and contextual metadata (specimen, biomarker role, evidence, provenance). Biomarker data and related annotations were either curated from publications or collected from public resources (e.g., OpenTargets, GWAS Catalog, ClinVar, CIViC, OncoMX) and were also contributed by the Common Fund Data Coordinating Centers and the Early Detection Research Network (EDRN). Standardization was achieved using ontologies and reference resources such as Disease Ontology, UBERON, UniProtKB, and HUGO Gene Nomenclature Committee (HGNC) gene symbols. BiomarkerKB data were ingested into a Neo4j-based knowledge graph and integrated with the Common Fund Data Ecosystem (CFDE) Knowledge Graph. The initial release of BiomarkerKB contains over 200,000 biomarker-disease associations spanning genes, proteins, metabolites, glycans, and chemical elements. The knowledge graph comprises more than 300,000 nodes and 1.2 million edges, enabling structured exploration of biomarker relationships within CFDE data as demonstrated through the knowledge graph query-based use cases presented in this study. A publicly accessible web portal (https://biomarkerkb.org) provides keyword search, filtering, data downloads, and access to graph visualization to support both researchers and computational analyses. BiomarkerKB addresses a critical gap in biomarker informatics by providing an integrated, FAIR (Findable, Accessible, Interoperable, and Reusable), and unified framework for biomarker knowledge exploration and discovery.

bioinformatics↗

The Adipomyokine Follistatin-like-1 Restores Cardiovascular Function in a Swine Model of Diabetic Myocardial Infarction

Obesity, diabetes, and metabolic syndrome increase the incidence and complicate the management of myocardial infarction (MI). Current treatments do not adequately blunt the progression to chronic ischemic heart disease and heart failure, making these diseases the largest cause of mortality worldwide. Insulin resistance and metabolic syndrome were induced in obese Ossabaw swine prior to ischemia/reperfusion injury-induced MI. Subcutaneous administration of the adipomyokine Follistatin-like-1 (recombinant non-glycosylated human FSTL1, ngFSTL1) for two weeks, beginning one month following myocardial infarction, decreased infarct necrosis, increased blood flow, and increased cardiomyocyte proliferation within the infarct region, leading to improved systolic and diastolic function. ngFSTL-1 also enhanced coronary and peripheral vascular function by increasing BKCa channel-dependent vasodilatory capacity. We conclude that subcutaneous ngFSTL1 ameliorated clinically relevant parameters of cardiac and vascular dysfunction in a preclinical swine model of diabetic MI, and suggest FSTL1 treatment may be broadly efficacious in humans. ARTICLE HIGHLIGHTSO_LISubcutaneous administration of recombinant human non-glycosylated FSTL1 (ngFSTL1) for 2 weeks, 1 month after infarction/reperfusion injury, improved cardiac function in a preclinical obese swine model of diabetic MI. C_LIO_LIngFSTL1 treatment induced cardiomyocyte proliferation and improved coronary perfusion, resulting in reduced necrosis of the infarct region. C_LIO_LIngFSTL1 treatment increased blood flow through peripheral arterioles, including cerebral and skeletal muscle, in addition to cardiac arterioles. C_LIO_LISystemic delivery of the non-glycosylated form of the adipomyokine FSTL1 might be an effective treatment for diabetic MI. C_LI

physiology↗

Summarizing Performance for Genome Scale Measurement of miRNA: Reference Samples and Metrics

BackgroundThe potential utility of microRNA as biomarkers for early detection of cancer and other diseases is being investigated with genome-scale profiling of differentially expressed microRNA. Processes for measurement assurance are critical components of genome-scale measurements. Here, we evaluated the utility of a set of total RNA samples, designed with between-sample differences in the relative abundance of miRNAs, as process controls.\n\nResultsThree pure total human RNA samples (brain, liver, and placenta) and two different mixtures of these components were evaluated as measurement assurance control samples on multiple measurement systems at multiple sites and over multiple rounds. In silico modeling of mixtures provided benchmark values for comparison with physical mixtures. Biomarker development laboratories using next-generation sequencing (NGS) or genome-scale hybridization assays participated in the study and returned data from the samples using their routine workflows. Multiplexed and single assay reverse-transcription PCR (RT-PCR) was used to confirm in silico predicted sample differences. Data visualizations and summary metrics for genome-scale miRNA profiling assessment were developed using this dataset, and a range of performance was observed. These metrics have been incorporated into an online data analysis pipeline and provide a convenient dashboard view of results from experiments following the described design. The website also serves as a repository for the accumulation of performance values providing new participants in the project an opportunity to learn what may be achievable with similar measurement processes.\n\nConclusionsThe set of reference samples used in this study provides benchmark values suitable for assessing genome-scale miRNA profiling processes. Incorporation of these metrics into an online resource allows laboratories to periodically evaluate their performance and assess any changes introduced into their measurement process.

genomics↗