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Börner, K.

Publications and source records attributed to Börner, K..

4 recordsLinked to original sources

Publication, Funding, and Experimental Data in Support of Human Reference Atlas Construction and Usage

Experts from 18 consortia are collaborating on the Human Reference Atlas (HRA) which aims to map the 37 trillion cells in the healthy human body. Information relevant for HRA construction and usage is held by experts (clinicians, pathologists, anatomists, single-cell experts), published in scholarly papers, and captured in experimental data. However, these data sources use different metadata schemes and cannot be cross-searched efficiently. This paper documents the compilation of a dataset, called HRAlit, that links the 136 HRA v1.4 digital objects (31 organs with 2,689 anatomical structures, 590 cell types, 1,770 biomarkers) to 583,117 experts; 7,103,180 publications; 896,680 funded projects, and 1,816 experimental datasets. The resulting HRAlit represents 23 tables with 21,704,001 records including 7 junction tables with 13,042,188 relationships. We demonstrate how HRAlit can be mined to identify leading experts, major papers, funding trends, or alignment with existing ontologies in support of systematic HRA construction and usage. Data and code are at https://github.com/cns-iu/hra-literature.

bioinformatics↗

Segmenting functional tissue units across human organs using community-driven development of generalizable machine learning algorithms

The development of a reference atlas of the healthy human body requires automated image segmentation of major anatomical structures across multiple organs based on spatial bioimages generated from various sources with differences in sample preparation. We present the setup and results of the "Hacking the Human Body" machine learning algorithm development competition hosted by the Human Biomolecular Atlas (HuBMAP) and the Human Protein Atlas (HPA) teams on the Kaggle platform. We showcase how 1,175 teams from 78 countries engaged in community- driven, open-science code development that resulted in machine learning models which successfully segment anatomical structures across five organs using histology images from two consortia and that will be productized in the HuBMAP data portal to process large datasets at scale in support of Human Reference Atlas construction. We discuss the benchmark data created for the competition, major challenges faced by the participants, and the winning models and strategies.

bioinformatics↗

Anatomical structures, cell types, and biomarkers of the healthy human blood vasculature

More than 150 scientists from 17 consortia are collaborating on an international project to build a Human Reference Atlas, which maps all 37 trillion cells in the healthy adult human body. The initial release of this atlas provided hierarchical lists of the anatomical structures, cell types, and biomarkers in 11 organs. Here, we describe the methods we used as part of this initiative to build the first open, computer-readable, and comprehensive database of the adult human blood vasculature, called the Human Reference Atlas-Vasculature Common Coordinate Framework (HRA-VCCF). It includes 961 vessels and their branching connections, 10 cell types, and 10 biomarkers. With this paper we are releasing additional details on vessel types and subtypes, branching sequence, anastomoses, portal systems, microvasculature, functional tissue units, mappings to regions vessels supply or drain, and links to 3D reference objects. Future versions will add variants, geometric properties of vessels, and connections to the lymph vasculature; and, it will iteratively expand and improve the database as additional experimental data become available through the participating consortia.

cell biology↗

Cone-shaped HIV-1 capsids are transported through intact nuclear pores

Human immunodeficiency virus (HIV-1) remains a major health threat. Viral capsid uncoating and nuclear import of the viral genome are critical for productive infection. The size of the HIV-1 capsid is generally believed to exceed the diameter of the nuclear pore complex (NPC), indicating that capsid uncoating has to occur prior to nuclear import. Here, we combined correlative light and electron microscopy with subtomogram averaging to capture the structural status of reverse transcription-competent HIV-1 complexes in infected T cells. We demonstrate that the diameter of the NPC in cellulo is sufficient for the import of apparently intact, coneshaped capsids. Subsequent to nuclear import, we detected disrupted and empty capsid fragments, indicating that uncoating of the replication complex occurs by breaking the capsid open, and not by disassembly into individual subunits. Our data directly visualize a key step in HIV-1 replication and enhance our mechanistic understanding of the viral life cycle.

microbiology↗