Format

Send to

Choose Destination
Sci Rep. 2019 Nov 26;9(1):17613. doi: 10.1038/s41598-019-54038-9.

Spa-RQ: an Image Analysis Tool to Visualise and Quantify Spatial Phenotypes Applied to Non-Small Cell Lung Cancer.

Author information

1
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, 00014, Finland.
2
Single-Cell Technologies Ltd, Szeged, Hungary.
3
Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
4
Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
5
Synthetic and Systems Biology Unit, Hungarian Academy of Sciences, Biological Research Center, Temesvári körút 62, 6726, Szeged, Hungary.
6
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, 00014, Finland. emmy.verschuren@helsinki.fi.

Abstract

To facilitate analysis of spatial tissue phenotypes, we created an open-source tool package named 'Spa-RQ' for 'Spatial tissue analysis: image Registration & Quantification'. Spa-RQ contains software for image registration (Spa-R) and quantitative analysis of DAB staining overlap (Spa-Q). It provides an easy-to-implement workflow for serial sectioning and staining as an alternative to multiplexed techniques. To demonstrate Spa-RQ's applicability, we analysed the spatial aspects of oncogenic KRAS-related signalling activities in non-small cell lung cancer (NSCLC). Using Spa-R in conjunction with ImageJ/Fiji, we first performed annotation-guided tumour-by-tumour phenotyping using multiple signalling markers. This analysis showed histopathology-selective activation of PI3K/AKT and MAPK signalling in Kras mutant murine tumours, as well as high p38MAPK stress signalling in p53 null murine NSCLC. Subsequently, Spa-RQ was applied to measure the co-activation of MAPK, AKT, and their mutual effector mTOR pathway in individual tumours. Both murine and clinical NSCLC samples could be stratified into 'MAPK/mTOR', 'AKT/mTOR', and 'Null' signature subclasses, suggesting mutually exclusive MAPK and AKT signalling activities. Spa-RQ thus provides a robust and easy to use tool that can be employed to identify spatially-distributed tissue phenotypes.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center