GeneSurfer Enables Transcriptome-wide Exploration and Functional Annotation of Gene Co-expression Modules in 3D Spatial Transcriptomics Data

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Gene co-expression provides crucial insights into biological functions, however, there is a lack of exploratory analysis tools for localized gene co-expression in large-scale datasets. We present GeneSurfer, an interactive interface designed to explore localized transcriptome-wide gene co-expression patterns in the 3D spatial domain. Key features of GeneSurfer include transcriptome-wide gene filtering and gene clustering based on spatial local co-expression within transcriptomically similar cells, multi-slice 3D rendering of average expression of gene clusters, and on-the-fly Gene Ontology term annotation of co-expressed gene sets. Additionally, GeneSurfer offers multiple linked views for investigating individual genes or gene co-expression in the spatial domain at each exploration stage. Demonstrating its utility with both spatial transcriptomics and single-cell RNA sequencing data from the Allen Brain Cell Atlas, GeneSurfer effectively identifies and annotates localized transcriptome-wide co-expression, providing biological insights and facilitating hypothesis generation and validation.

Authors 7

1. Chang Li corresponding Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

   Leiden University Medical Center

2. Julian Thijssen Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

   Leiden University Medical Center

3. Thomas Kroes Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

   Leiden University Medical Center

4. Ximaine R. van der Burg Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

   Leiden University Medical Center

5. Louise van der Weerd Aachen Department of Human Genetics Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

   Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

   Leiden University Medical Center

6. Thomas Höllt

   Delft University of Technology

   Affiliation as printed

   Computer Graphics and Visualization, INSY, TU Delft, 2628 XE Delft, The Netherlands

   TU Delft

7. Boudewijn P. F. Lelieveldt Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Delft Bioinformatics Lab, INSY, TU Delft, 2628 XE Delft, The Netherlands

   Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

   Leiden University Medical Center