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other·preclinical research, biomedical research, research methods, gastroenterology·PMC10615476

Defining spatiotemporal gene modules in liver regeneration using Analytical Dynamic Visual Spatial Omics Representation (ADViSOR)

Hepatology Communications · 6 authors, 5 centres

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The pipeline, comprising Time-Interval Principal Component Analysis and sliding dynamic hypergraphs, was applied to serial data on 100 preselected genes, including components of the Wnt/β-catenin pathway. Key findings include the identification of functional gene modules, inference that macrophage-mediated inflammation is critical in early regeneration, and confirmation that *Ccnd1* is regulated by the Wnt/β-catenin pathway. The study positions ADViSOR as a hypothesis-generating tool for spatiotemporal contexts, validated partially by protein localization.

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preclinical research

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AI pipeline

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ORIGINAL PAPER

PMC10615476

Defining spatiotemporal gene modules in liver regeneration using Analytical Dynamic Visual Spatial Omics Representation (ADViSOR)

Hepatology Communications

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ABSTRACT

Background: The liver is the only organ with the ability to regenerate following surgical or toxicant insults, and partial hepatectomy serves as an experimental model of liver regeneration (LR). Dynamic changes in gene expression occur from the periportal to pericentral regions of the liver following partial hepatectomy; thus, spatial transcriptomics, combined with a novel computational pipeline (ADViSOR [Analytic Dynamic Visual Spatial Omics Representation]), was employed to gain insights into the spatiotemporal molecular underpinnings of LR. Methods: ADViSOR, comprising Time-Interval Principal Component Analysis and sliding dynamic hypergraphs, was applied to spatial transcriptomics data on 100 genes assayed serially through LR, including key components of the Wnt/β-catenin pathway at critical timepoints after partial hepatectomy. Results: This computational pipeline identified key functional modules demonstrating cell signaling and cell-cell interactions, inferring shared regulatory mechanisms. Specifically, ADViSOR analysis suggested that macrophage-mediated inflammation is a critical component of early LR and confirmed prior studies showing that Ccnd1 , a hepatocyte proliferative gene, is regulated by the Wnt/β-catenin pathway. These findings were subsequently validated through protein localization, which provided further confirmation and novel insights into the spatiotemporal changes in the Wnt/β-catenin pathway during LR. Conclusions: Thus, ADViSOR may yield novel insights in other complex, spatiotemporal contexts.

CITATION EXPORT

Anya Singh-Varma, Ashti M. Shah, Silvia Liu et al.. Defining spatiotemporal gene modules in liver regeneration using Analytical Dynamic Visual Spatial Omics Representation (ADViSOR). Hepatology Communications. (2023). https://doi.org/10.1097/HC9.0000000000000289

AUTHORS

6 · 5 CENTRES

Anya Singh-Varma, Ashti M. Shah, Silvia Liu, Ruben Zamora, Satdarshan P. Monga, Yoram Vodovotz

1Department of Pathology, Division of Experimental Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
2Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh, Pittsburgh, Pennsylvania, USA
3Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
4Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
5Center for Inflammation and Regeneration Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA