Ziai, J. | bioRxiv Science

bioRxiv2022

SPEX: A modular end-to-end analytics tool for spatially resolved omics of tissues

Recent advancements in transcriptomics and proteomics have opened the possibility for spatially resolved molecular characterization of tissue architecture with the promise of enabling a deeper understanding of tissue biology in either homeostasis or disease. The wealth of data generated by these technologies has recently driven the development of a wide range of computational methods. These methods have the requirement of advanced coding fluency to be applied and integrated across the full spatial omics analysis process thus presenting a hurdle for widespread adoption by the biology research community. To address this, we introduce SPEX (Spatial Expression Explorer), a web-based analysis platform that employs modular analysis pipeline design, accessible through a user-friendly interface. SPEXs infrastructure allows for streamlined access to open source image data management systems,analysis modules, and fully integrated data visualization solutions. Analysis modules include essential steps covering image processing, single-cell and spatial analysis. We demonstrate SPEXs ability to facilitate the discovery of biological insights in spatially resolved omics datasets from healthy tissue to tumor samples.

bioinformatics↗

bioRxiv2022

Loss of the intracellular enzyme QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity

Tumor-associated macrophages are composed of distinct populations arising from monocytes or tissue macrophages, with a poorly understood link to disease pathogenesis. Here, we demonstrate that mouse monocyte migration was supported by glutaminyl-peptide cyclotransferase-like (QPCTL), an enzyme that mediates N-terminal modification of several subtrates, including the monocyte-chemoattractants CCL2 and CCL7, protecting them from proteolytic inactivation. Knockout of Qpctl disrupted monocyte homeostasis, attenuated tumor growth and reshaped myeloid cell infiltration, with loss of monocyte-derived populations with immunosuppressive and pro-angiogenic profiles. Antibody blockade of the receptor CSF1R, which more broadly eliminates tissue macrophages, reversed tumor growth inhibition in Qpctl-/- mice, and prevented lymphocyte infiltration. Modulation of QPCTL synergized with anti-PD-L1 to expand CD8+ T cells and limit tumor growth. QPCTL inhibition constitutes an effective approach for myeloid cell-targeted cancer immunotherapy.

immunology↗