The advent of advanced robotic platforms and workflow automation tools has revolutionized the landscape of biological research, offering unprecedented levels of precision, reproducibility, and versatility in experimental design. In this work, we present an automated and modular workflow for exploring cell behavior in two-dimensional culture systems. By integrating the BioAssemblyBot (BAB) robotic platform and the BioApps™ workflow automater with live-cell fluorescence microscopy, our workflow facilitates execution and analysis of migration and proliferation assays.
View Article and Find Full Text PDFBiomarkers enable objective monitoring of a given cell or state in a biological system and are widely used in research, biomanufacturing, and clinical practice. However, identifying appropriate biomarkers that are both robustly measurable and capture a state accurately remains challenging. We present a framework for biomarker identification based upon observability guided sensor selection.
View Article and Find Full Text PDFBackground: With more clinical trials are offering optional participation in the collection of bio-specimens for biobanking comes the increasing complexity of requirements of informed consent forms. The aim of this study is to develop an automatic natural language processing (NLP) tool to annotate informed consent documents to promote biorepository data regulation, sharing, and decision support. We collected informed consent documents from several publicly available sources, then manually annotated them, covering sentences containing permission information about the sharing of either bio-specimens or donor data, or conducting genetic research or future research using bio-specimens or donor data.
View Article and Find Full Text PDFAdipose tissue macrophage (ATM) infiltration is associated with adipose tissue dysfunction and insulin resistance in mice and humans. Recent single-cell data highlight increased ATM heterogeneity in obesity but do not provide a spatial context for ATM phenotype dynamics. We integrated single-cell RNA-Seq, spatial transcriptomics, and imaging of murine adipose tissue in a time course study of diet-induced obesity.
View Article and Find Full Text PDFRecent advances in biological technologies, such as multi-way chromosome conformation capture (3C), require development of methods for analysis of multi-way interactions. Hypergraphs are mathematically tractable objects that can be utilized to precisely represent and analyze multi-way interactions. Here we present the Hypergraph Analysis Toolbox (HAT), a software package for visualization and analysis of multi-way interactions in complex systems.
View Article and Find Full Text PDFThe purpose of this study was to evaluate, revise, and extend the Informed Consent Ontology (ICO) for expressing clinical permissions, including reuse of residual clinical biospecimens and health data. This study followed a formative evaluation design and used a bottom-up modeling approach. Data were collected from the literature on US federal regulations and a study of clinical consent forms.
View Article and Find Full Text PDFChromatin architecture, a key regulator of gene expression, can be inferred using chromatin contact data from chromosome conformation capture, or Hi-C. However, classical Hi-C does not preserve multi-way contacts. Here we use long sequencing reads to map genome-wide multi-way contacts and investigate higher order chromatin organization in the human genome.
View Article and Find Full Text PDFThe informed consent process is a complicated procedure involving permissions as well a variety of entities and actions. In this paper, we discuss the use of Semantic Web Rule Language (SWRL) to further extend the Informed Consent Ontology (ICO) to allow for semantic machine-based reasoning to manage and generate important permission-based information that can later be viewed by stakeholders. We present four use cases of permissions from the All of Us informed consent document and translate these permissions into SWRL expressions to extend and operationalize ICO.
View Article and Find Full Text PDFEvery human somatic cell inherits a maternal and a paternal genome, which work together to give rise to cellular phenotypes. However, the allele-specific relationship between gene expression and genome structure through the cell cycle is largely unknown. By integrating haplotype-resolved genome-wide chromosome conformation capture, mature and nascent mRNA, and protein binding data from a B lymphoblastoid cell line, we investigate this relationship both globally and locally.
View Article and Find Full Text PDFThe mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with their own immunological objectives. The affinity maturation process is widely viewed as a heuristic to solve the global optimization problem of finding B cells with high affinity to the antigen.
View Article and Find Full Text PDFBackground: The lack of machine-interpretable representations of consent permissions precludes development of tools that act upon permissions across information ecosystems, at scale.
Objectives: To report the process, results, and lessons learned while annotating permissions in clinical consent forms.
Methods: We conducted a retrospective analysis of clinical consent forms.
Reducing unplanned readmissions is a major focus of current hospital quality efforts. In order to avoid unfair penalization, administrators and policymakers use prediction models to adjust for the performance of hospitals from healthcare claims data. Regression-based models are a commonly utilized method for such risk-standardization across hospitals; however, these models often suffer in accuracy.
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