Spatial Transcriptomics Enhances Biological Interpretation of GX Signatures


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Precise mechanism-based gene expression signatures (GES) have been developed in appropriate in vitro and in vivo model systems to identify important cancer-related signaling processes. However, some GESs originally developed to represent specific disease processes, primarily with an epithelial cell focus, are being applied to heterogeneous tumor samples where the expression of the genes in the signature may no longer be epithelial-specific. Therefore, unknowingly, even small changes in tumor stroma percentage can directly influence GESs, undermining the intended mechanistic signaling.

Using colorectal cancer as an example, we deployed numerous orthogonal profiling methodologies, including laser capture microdissection, flow cytometry, bulk and multiregional biopsy clinical samples, single-cell RNA sequencing and finally spatial transcriptomics, to perform a comprehensive assessment of whether GESs are confounded by stromal content in tumor tissue. Findings in this webinar demonstrate the clear potential for misinterpretation of the meaning of GESs, due to widespread stromal influences, which in-turn can undermine faithful alignment between clinical samples and preclinical data/models, particularly cell lines and organoids, or tumor models not fully recapitulating the stromal and immune microenvironment.

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Circular portrait of Amy Johnson

Amy Johnson, PhD

District Sales Manager, NanoString Technologies

Amy Johnson is a District Sales Manager for the Mid-Atlantic region at NanoString Technologies. Prior to her current role, Amy was a Technical Sales Specialist focused on NanoString Technologies’ GeoMx Digital Spatial Profiler and CosMx Spatial Molecular Imager platforms. Amy earned her PhD in nutritional biochemistry and completed her postdoctoral training in the Department of Nutrition at UNC-Chapel Hill. From fetal brain development to immunometabolism in obesity, she has used in vitro and in vivo model systems as well as human study populations to research the interplay between genetic variation in metabolic pathway enzymes and individual health.

Circular portrait of Robert Yamulla

Robert Yamulla, PhD

Senior Marketing Manager, AMR Cancer Research, Illumina

Robert Yamulla, PhD, leads Illumina’s cancer research marketing strategy for North and South America. He is a cancer biologist specializing in next-generation sequencing, CRISPR/Cas9, and in vitro disease modeling. Robert received his PhD from Cornell University. His most recent research focused on identifying fundamental initiation mechanisms and causative factors for ovarian carcinoma. He has also developed mechanistic models of colon cancer progression as a Howard Hughes Medical Institute research fellow and studied rare genetic diseases with the Clinic for Special Children in Lancaster, Pennsylvania.

Circular portrait of Nigel Jamieson

Nigel Jamieson MD PhD

Clinical Senior Lecturer and Consultant HPB Surgeon; Clinician Scientist, Cancer Research UK; School of Cancer Sciences, Glasgow Royal Infirmary, University of Glasgow

Nigel Jamieson is a Clinical Senior Lecturer within the Institute of Cancer Sciences and an Honorary Consultant HPB surgeon at Glasgow Royal Infirmary. He has contributed to over 130 peer reviewed publications and has an active role in the development and management of the Precision-Panc platform; his laboratory group focuses on the interaction between the immune microenvironment and chemotherapy in the tumors of patients with pancreatic cancer and has established a spatial transcriptomic facility characterizing multiple malignancies, premalignant lesions, and inflammatory conditions. He works closely with Pancreatic Cancer UK and is part of a national group aiming to standardize care for patients with pancreatic cancer across the UK.