Intracellular spatial transcriptomic analysis toolkit (InSTAnT)

Anurendra Kumar, Alex W. Schrader, Bhavay Aggarwal, Ali Ebrahimpour Boroojeny, Marisa Asadian, JuYeon Lee, You Jin Song, Sihai Dave Zhao (), Hee-Sun Han () and Saurabh Sinha ()
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Anurendra Kumar: Georgia Institute of Technology
Alex W. Schrader: University of Illinois Urbana-Champaign
Bhavay Aggarwal: Georgia Institute of Technology
Ali Ebrahimpour Boroojeny: University of Illinois Urbana-Champaign
Marisa Asadian: University of Illinois Urbana-Champaign
JuYeon Lee: University of Illinois Urbana-Champaign
You Jin Song: University of Illinois Urbana-Champaign
Sihai Dave Zhao: University of Illinois Urbana-Champaign
Hee-Sun Han: University of Illinois Urbana-Champaign
Saurabh Sinha: Georgia Institute of Technology

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Imaging-based spatial transcriptomics technologies such as Multiplexed error-robust fluorescence in situ hybridization (MERFISH) can capture cellular processes in unparalleled detail. However, rigorous and robust analytical tools are needed to unlock their full potential for discovering subcellular biological patterns. We present Intracellular Spatial Transcriptomic Analysis Toolkit (InSTAnT), a computational toolkit for extracting molecular relationships from spatial transcriptomics data at single molecule resolution. InSTAnT employs specialized statistical tests and algorithms to detect gene pairs and modules exhibiting intriguing patterns of co-localization, both within individual cells and across the cellular landscape. We showcase the toolkit on five different datasets representing two different cell lines, two brain structures, two species, and three different technologies. We perform rigorous statistical assessment of discovered co-localization patterns, find supporting evidence from databases and RNA interactions, and identify associated subcellular domains. We uncover several cell type and region-specific gene co-localizations within the brain. Intra-cellular spatial patterns discovered by InSTAnT mirror diverse molecular relationships, including RNA interactions and shared sub-cellular localization or function, providing a rich compendium of testable hypotheses regarding molecular functions.

Date: 2024
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DOI: 10.1038/s41467-024-49457-w

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