Dataset Information

Holographic Reconstruction of Axonal Pathways in the Human Brain.

ABSTRACT: Three-dimensional documentation of the axonal pathways connecting gray matter components of the human brain has wide-ranging scientific and clinical applications. Recent attempts to map human structural connectomes have concentrated on using tractography results derived from diffusion-weighted imaging data, but tractography is an indirect method with numerous limitations. Advances in holographic visualization platforms provide a new medium to integrate anatomical data, as well as a novel working environment for collaborative interaction between neuroanatomists and brain-imaging scientists. Therefore, we developed the first holographic interface for building axonal pathways, populated it with human histological and structural MRI data, and assembled world expert neuroanatomists to interactively define axonal trajectories of the cortical, basal ganglia, and cerebellar systems. This blending of advanced visualization hardware, software development, and neuroanatomy data enabled the translation of decades of amassed knowledge into a human axonal pathway atlas that can be applied to educational, scientific, or clinical investigations.

SUBMITTER: Petersen MV

PROVIDER: S-EPMC6948195 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Holographic Reconstruction of Axonal Pathways in the Human Brain.

Petersen Mikkel V MV Mlakar Jeffrey J Haber Suzanne N SN Parent Martin M Smith Yoland Y Strick Peter L PL Griswold Mark A MA McIntyre Cameron C CC

Neuron 20191107 6

Three-dimensional documentation of the axonal pathways connecting gray matter components of the human brain has wide-ranging scientific and clinical applications. Recent attempts to map human structural connectomes have concentrated on using tractography results derived from diffusion-weighted imaging data, but tractography is an indirect method with numerous limitations. Advances in holographic visualization platforms provide a new medium to integrate anatomical data, as well as a novel working ...[more]

PMID: 31708306

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Project description:Signaling pathways are a cornerstone of systems biology. Several databases store high-quality representations of these pathways that are amenable for automated analyses. Despite painstaking and manual curation, these databases remain incomplete. We present PATHLINKER, a new computational method to reconstruct the interactions in a signaling pathway of interest. PATHLINKER efficiently computes multiple short paths from the receptors to transcriptional regulators (TRs) in a pathway within a background protein interaction network. We use PATHLINKER to accurately reconstruct a comprehensive set of signaling pathways from the NetPath and KEGG databases. We show that PATHLINKER has higher precision and recall than several state-of-the-art algorithms, while also ensuring that the resulting network connects receptor proteins to TRs. PATHLINKER's reconstruction of the Wnt pathway identified CFTR, an ABC class chloride ion channel transporter, as a novel intermediary that facilitates the signaling of Ryk to Dab2, which are known components of Wnt/β-catenin signaling. In HEK293 cells, we show that the Ryk-CFTR-Dab2 path is a novel amplifier of β-catenin signaling specifically in response to Wnt 1, 2, 3, and 3a of the 11 Wnts tested. PATHLINKER captures the structure of signaling pathways as represented in pathway databases better than existing methods. PATHLINKER's success in reconstructing pathways from NetPath and KEGG databases point to its applicability for complementing manual curation of these databases. PATHLINKER may serve as a promising approach for prioritizing proteins and interactions for experimental study, as illustrated by its discovery of a novel pathway in Wnt/β-catenin signaling. Our supplementary website at http://bioinformatics.cs.vt.edu/~murali/supplements/2016-sys-bio-applications-pathlinker/ provides links to the PATHLINKER software, input datasets, PATHLINKER reconstructions of NetPath pathways, and links to interactive visualizations of these reconstructions on GraphSpace.

Dataset Information

Holographic Reconstruction of Axonal Pathways in the Human Brain.

Publications

Holographic Reconstruction of Axonal Pathways in the Human Brain.

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