Data preprocessing

This section contains description of preprocessing of Stereo-seq data.

Stereo-seq Analysis Workflow

Stereo-seq sequencing data were preprocessed using SAW to generation spatial gene expression matrices in GEM format.

Image files, which are usually in TIFF format, generated during the stereo-seq library construction process should be ready for further process together with the GEM files.

Note

Data of each section were packed with a sinlge Tissue Section ID in STOmicsDB database, including staining image (.tif), GEM file (.gem) as well as relevant annotation information (.txt), and can be accessed with [STTS0000461 - 515].

GEM file and TIFF file for each chip were manually cropped according to the ROI region to extract the expression and image data of each individual in the tissue section.

Image registration

Each pair of GEM file and TIFF file was then went through image registration following MIRROR pipeline.

  • input:

    • gem file

    • image file

  • output:

    • affine transformation matrix

Cell boundary detection

Each ssDNA image was went through object detection and cell segmentation following Detect cell boundaries based on ssDNA images.

  • input:

    • image file

  • output:

    • cell mask matrix

DNB aggregation

With cell mask and affine transformation matrix, the original gem file would be aggregated into putative cells following cell aggregation.

  • input:

    • affine transformation matrix

    • cell mask matrix

    • gem file

  • output:

    • cell-gene expression matrix in h5d format

Cell clustering

The generated Cell-by-gene matrix of each individual was processed following the Seurat integration workflow, from which the clustering results were manually annotated to obtain lineage information of each cluster.

  • input:

    • cell-gene matrix

  • output:

    • cell-lineage annotation

3D alignment

Serial annotation images were aligned by the similarities of morphology and annotation color code pair by pair folling SEAM Pipeline.

  • input:

    • cell-lineage annotation

    • images

  • output:

    • aligned 3D coordinates

3D mesh building

With the aligned 3D coordinates and cell annotation, tissue level triangular meshes were constructed folling Mesh generation pipeline.

  • input:

    • 3D coordinates

  • output:

    • triangular meshes