Deep Phenotyping

Using our Ventana Discovery Ultra autostainers in combination with the Akoya PhenoImager HT, we routinely detect up to 6 genes of interest on the same tissue section, allowing us to answer complex questions about tumour biology in a high-throughput manner. We are leaders in this technology, and have collaborations with leading industry providers as well as numerous academic partners. We believe multiplex assays on this scale are likely to form the basis of the next generation of clinical biomarkers, and are working towards translating our assays into a clinical setting.

Over 2025, we have worked with 14 research groups with this technology, and we have several manuscripts in preparation. We have developed panels for human prostate cancer (Leung, Pearson), human pancreatic ductal adenocarcinoma (Campbell), human colorectal cancer (Roxburgh), mouse models of hepatocellular carcinoma (Bird), cholangiocarcinoma (Braconi), and both human and mouse models of malignant mesothelioma (Chalmers, Murphy).

Using our Akoya PhenoCycler Fusion, we can detect up to 100 proteins of interest within intact tissue context. Our expertise with this platform has led to several large in-depth phenotyping collaborations, including our involvement in the SAMBAI Cancer Grand Challenge. This project is a multi-centre international effort to tackle cancer inequities in minority and socially deprived patient populations. In addition, we have collaborations with the Pearson lab at Cardiff University, focusing on fibroblast subtypes in human prostate cancer, and locally with the Chang, Inman and Le Quesne labs focusing on fibroblast subtyping and immune phenotypes in human malignancies, and the Morton lab in mouse models of pancreatic cancer.

We have a methods paper detailing our in-depth validation protocol in process, and our custom PDAC panel has been presented at several meetings. This panel of 43 markers simultaneously detects expression of numerous markers of epithelial and fibroblast plasticity, new therapeutic targets, and highly detailed immunophenotypes. A murine version of this panel is in preparation.

Our 10x Genomics Xenium platform enables detection of up to 5,100 genes of interest in a single tissue section. The custom gene expression chemistry has been used by our collaborators to develop panels detecting multiple species simultaneously in parasite-infected animal tissues, and also to detect single nucleotide variants in mRNA. Furthermore, the Xenium can be combined with PhenoCycler Fusion, enabling extremely high-plex multi-omic detection of RNA and protein within the same tissue section. Of note, the Xenium is part of our SAMBAI Cancer Grand Challenge work package.

The Xenium is a key technology for the CRC STARS project, and data from our first mouse custom gene expression panel has been published in Nature by the Sansom lab.

Visiopharm is our image analysis platform of choice. We have developed bespoke deep learning pipelines for several diseased tissues and tumour types, supporting high-throughput analysis of the images generated by our spatial platforms. We offer training for collaborators wanting to generate their own data, or we design custom workflows and run them as part of our deep phenotyping service.

This year we have published a manuscript in PLOS ONE describing a novel deep learning classifier we have developed using the deep learning tools within Visiopharm, which accurately predicts cellular phenotypes without the need for accurate cell boundary classification.

The Lunaphore COMET enables the detection of up to 40 proteins, or 12 RNAScope targets and 24 proteins, on the same tissue section. We have established both human and murine immuno-oncology panels for our collaborators to build on. We have also developed multiomic panels for the Sansom and Dasgupta labs.

This year, we have added the Visium to our facility, offering whole transcriptome analysis using the CytAssist. This can be used as a standalone technology, or in combination with any of the platforms mentioned above.

As a team we are engaged in the translation of our multiplex and high-plex research assays to the clinic, where they can help answer complex diagnostic questions, and ultimately be used as clinical biomarkers in the future.

We believe lower-plex chromogenic multiplex assays using 3 or 4 dyes visible by eye are the way to achieve this, and we have several collaborations in this area.