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bioRxiv · 10.1101/2025.02.11.637442

A bioinformatic workflow to facilitate the study of less-understood proteins: the case of SH2D2A

Gilmour, B. C.·Chan, H.·Singh, S.·Nyman, T. A.·Borowicz, P.·Phuyal, S.·Spurkland, A.
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Abstract

Adaptor proteins are key regulators of immune signalling but are challenging to study due to redundant pathways that obscure clear functional "anchor" phenotypes. Making use of public single-cell RNA sequencing (scRNA-seq) datasets, we theorised that anchors could be identified by working in the reverse direction: starting from the transcriptomic level and working "bottom-up" to identify anchoring phenomena at the cell surface. We have produced a prototype workflow for this method using the case of the lymphocyte-enriched adaptor protein SH2D2A, whose function remains uncertain. Using our bottom-up analysis, we have identified a link between SH2D2A and T cell-T cell (T-T) synapses enriched for ITGB2. The functional implications of this link are currently being explored, but further application of this bioinformatic approach to less-understood proteins may prove useful in understanding the minutiae of immune cell signalling, with implications for immunotherapy.

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Gilmour, B. C., Chan, H., Singh, S., Nyman, T. A., Borowicz, P., Phuyal, S., Spurkland, A.. 2025-02-12. A bioinformatic workflow to facilitate the study of less-understood proteins: the case of SH2D2A. https://doi.org/10.1101/2025.02.11.637442

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