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      Pancreatlas: Applying an Adaptable Framework to Map the Human Pancreas in Health and Disease

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          Summary

          Human tissue phenotyping generates complex spatial information from numerous imaging modalities, yet images typically become static figures for publication, and original data and metadata are rarely available. While comprehensive image maps exist for some organs, most resources have limited support for multiplexed imaging or have non-intuitive user interfaces. Therefore, we built a Pancreatlas resource that integrates several technologies into a unique interface, allowing users to access richly annotated web pages, drill down to individual images, and deeply explore data online. The current version of Pancreatlas contains over 800 unique images acquired by whole-slide scanning, confocal microscopy, and imaging mass cytometry, and is available at https://www.pancreatlas.org. To create this human pancreas-specific biological imaging resource, we developed a React-based web application and Python-based application programming interface, collectively called Flexible Framework for Integrating and Navigating Data (FFIND), which can be adapted beyond Pancreatlas to meet countless imaging or other structured data-management needs.

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          Highlights

          • Human organ phenotyping databases benefit from intuitive user interfaces

          • Pancreatlas resource enables exploration of bioimaging data from human pancreas

          • The front-end framework of Pancreatlas, FFIND, is modular and easily adaptable

          • FFIND provides structured data-exploration capabilities across countless domains

          The Bigger Picture

          Scientists need cost-effective yet fully featured database solutions that facilitate large dataset sharing in a structured and easily digestible manner. Flexible Framework for Integrating and Navigating Data (FFIND) is a data-agnostic web application that is designed to easily connect existing databases with data-browsing clients. We used FFIND to build Pancreatlas, an online imaging resource containing datasets linking imaging data with clinical data to facilitate advances in the understanding of diabetes, pancreatitis, and pancreatic cancer. FFIND architecture, which is available as open-source software, can be easily adapted to meet other field- or project-specific needs; we hope it will help data scientists reach a broader audience by reducing the development life cycle and providing familiar interactivity in communicating data and underlying stories.

          Abstract

          Human tissue phenotyping generates complex imaging data that is difficult to share in publications, and many organ-specific databases lack intuitive user interfaces or have limited support for multiplexed imaging. Therefore, we built a Pancreatlas resource ( https://www.pancreatlas.org) that integrates several technologies into a unique interface, allowing users to access richly annotated web pages. To create this imaging resource, we developed a data-agnostic, React-based web application and Python-based application programming interface, collectively called Flexible Framework for Integrating and Navigating Data (FFIND; https://github.com/Powers-Brissova-Research-Group/FFIND).

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          Most cited references36

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          The FAIR Guiding Principles for scientific data management and stewardship

          There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.
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            An anatomically comprehensive atlas of the adult human brain transcriptome.

            Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ∼900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography-the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.
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              Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging

              Summary A highly multiplexed cytometric imaging approach, termed co-detection by indexing (CODEX), is used here to create multiplexed datasets of normal and lupus (MRL/lpr) murine spleens. CODEX iteratively visualizes antibody binding events using DNA barcodes, fluorescent dNTP analogs, and an in situ polymerization-based indexing procedure. An algorithmic pipeline for single-cell antigen quantification in tightly packed tissues was developed and used to overlay well-known morphological features with de novo characterization of lymphoid tissue architecture at a single-cell and cellular neighborhood levels. We observed an unexpected, profound impact of the cellular neighborhood on the expression of protein receptors on immune cells. By comparing normal murine spleen to spleens from animals with systemic autoimmune disease (MRL/lpr), extensive and previously uncharacterized splenic cell-interaction dynamics in the healthy versus diseased state was observed. The fidelity of multiplexed spatial cytometry demonstrated here allows for quantitative systemic characterization of tissue architecture in normal and clinically aberrant samples.
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                Author and article information

                Contributors
                Journal
                Patterns (N Y)
                Patterns (N Y)
                Patterns
                Elsevier
                2666-3899
                05 October 2020
                13 November 2020
                05 October 2020
                : 1
                : 8
                : 100120
                Affiliations
                [1 ]Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
                [2 ]Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, Diabetes Institute, University of Florida, Gainesville, FL, USA
                [3 ]Department of Pediatrics, College of Medicine, Diabetes Institute, University of Florida, Gainesville, FL, USA
                [4 ]VA Tennessee Valley Healthcare System, Nashville, TN, USA
                [5 ]Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA
                [6 ]Creative Data Solutions Shared Resource, Center for Stem Cell Biology, Vanderbilt University, Nashville, TN, USA
                Author notes
                []Corresponding author jp.cartailler@ 123456vanderbilt.edu
                [∗∗ ]Corresponding author marcela.brissova@ 123456vumc.org
                [7]

                These authors contributed equally

                [8]

                Lead Contact

                Article
                S2666-3899(20)30161-6 100120
                10.1016/j.patter.2020.100120
                7691395
                33294866
                e65501d3-59c0-4aee-b83d-654c50297e5d
                © 2020 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 19 March 2020
                : 31 August 2020
                : 14 September 2020
                Categories
                Descriptor

                application programming interface,data integration,data publication and archiving,human pancreas development,imaging databases,microscopy,open source,pancreas imaging,software,diabetes,web resource

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