Spatial Sequencing Case Studies
Explore the early collaborators and spatial projects
being run on the G4X.
G4X Spatial Research Grant Winners
Multi-omic Mapping of Lung Cancer Evolution from Primary to Metastasis in the PEACE Autopsy Study
University College London & Cancer Research UK
Research autopsies in the PEACE study have shed light on evolutionary nature of metastases and the environment in which they arise. Early findings in lung cancer have demonstrated cellular migration patterns that distinguish primary-to-metastasis and metastasis-to-metastasis seeding, and the role of genome instability in metastatic dissemination. This project will investigate the interplay between the tumour microenvironment and the somatic genome, and how this evolves in response to therapy.
Miriam Jamal-Hanjani
Eduard Porta
Nicholas McGranahan
Resistance to Immune Checkpoint Inhibitors in Clear Cell Renal Cell Carcinoma (ccRCC)
The Netherlands Cancer Institute (NKI)
Resistance to immune checkpoint inhibitors (ICIs) is an important clinical problem among patients with ccRCC. In this research project we aim to identify tumor-reactive and dysfunctional T-cells in ccRCC tumors after neoadjuvant ICIs and assess their spatial relationship with other cells in the microenvironment to elucidate the resistance mechanisms.
Femke Burgers, MD
Koen van der Mijn
Roderick Beijersbergen
Spatially Resolving the Cellular and Molecular Microenvironment in Perianal Fistulizing Crohn’s Disease
Imperial College London
Perianal fistulas are the most feared complication of Crohn’s disease driven by dysregulated inflammatory responses that drive epithelial-to-mesenchymal transition and tissue remodelling in perianal Crohn’s disease (pCD). Using spatially resolved transcriptomics, we aim to decode the crosstalk between immune and non-immune cells in pCD and in the process identify new therapeutic targets that can be harnessed in its treatment.
Dr. Laura Constable
Defining the Spatial Landscape of Renal Carcinoma Metastases
University of Michigan
Perianal fistulas are the most feared complication of Crohn’s disease driven by dysregulated inflammatory responses that drive epithelial-to-mesenchymal transition and tissue remodelling in perianal Crohn’s disease (pCD). Using spatially resolved transcriptomics, we aim to decode the crosstalk between immune and non-immune cells in pCD and in the process identify new therapeutic targets that can be harnessed in its treatment.
Evan Keller DVM, PhD
Allison M May MD
Multi-omic Mapping of Lung Cancer Evolution from Primary to Metastasis in the PEACE Autopsy Study
University College London & Cancer Research UK
Research autopsies in the PEACE study have shed light on evolutionary nature of metastases and the environment in which they arise. Early findings in lung cancer have demonstrated cellular migration patterns that distinguish primary-to-metastasis and metastasis-to-metastasis seeding, and the role of genome instability in metastatic dissemination. This project will investigate the interplay between the tumour microenvironment and the somatic genome, and how this evolves in response to therapy.
Miriam Jamal-Hanjani
Eduard Porta
Nicholas McGranahan
Previous Projects
Dr. Catherine Wu
Chief, Stem Cell Transplantation & Cellular Therapies
Harvard Medical School, Dana Farber Cancer Institute
“The high sample throughput and the excellent data quality that has been generated on the G4X with our bone marrow samples—notoriously a very difficult tissue type—have been impressive and have allowed us to envision much larger studies that have not been previously possible. “The scale provided by the G4X promises to have a tremendous impact on expanding our understanding of the tumor microenvironment in acute myelogenous leukemia (AML) and beyond.”
Differential Response to Treatment in AML
The Wu Lab, in this study, surveyed bone marrow biopsies in 12 patients exposed to donor lymphocyte infusion after relapsing from prior immunotherapy. Through a panel of 150 transcript targets and 10 protein targets, the Wu lab was able to process 35 bone marrow biopsy sections – some as old as 12 years old – in a single G4X run, profiling transcripts and proteins in very challenging samples.
Dr. Paul Blainey
Core Faculty Member & Associate Professor of Biological Engineering
Broad Institute of MIT & Harvard
“The high sample throughput and the excellent data quality that has been generated on the G4X with our bone marrow samples—notoriously a very difficult tissue type—have been impressive and have allowed us to envision much larger studies that have not been previously possible. “The scale provided by the G4X promises to have a tremendous impact on expanding our understanding of the tumor microenvironment in acute myelogenous leukemia (AML) and beyond.”
In Situ Sequencing of CRISPR Guide RNA + Protein + H&E imaging
As part of an optical pooled screen study, the Blainey Lab leveraged Direct-Seq, a novel technique being developed by Singular Genomics that directly sequences variable regions of interest, to survey CRISPR perturbations in HeLa and A549 cells. A library of 40 CRISPR guide RNAs were used for this study and 1.2M cells per flow cell were processed on the G4X with a sequencing cycle time of under 5 minutes per cycle during Direct-Seq readout.
- 30 cycles
- 1-20 bp variable
- 21-30 bp fixed
Direct-Seq (sgRNA)
2-plex protein
Fluorescent H&E
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