Spatial analysis of cellular arrangement using quantitative, single-cell imaging of protein multiplexing
Bibliographic record
Abstract
Single cell phenotyping using molecular or protein multiplexing techniques is gaining momentum, especially in the characterization of cancer and the tumor microenvironment. It has proven to be particularly useful in studying the extent of heterogeneity in cancer, and in the profiling of the immune environment to assess whether certain cell subsets could be predictive of treatment response. Using a sequential protein marker labelling system called Multiplex Immunofluorescence (MxIF, GE Research), we have developed quantitative image analysis and computational tools for phenotyping individual immune and cancer cells for various cancer types. The expressions of T cell markers CD3, CD8, macrophage markers CD68, immune checkpoint proteins PD-1 and PD-L1, together with proliferative marker (Ki67) and cancer-specific marker PCK (pan-Cytokeratin) were studied on single 4um sections of formalin-fixed, paraffinembedded (FFPE) ovarian cancer tissue sections. We explored the composition of immune phenotype using t-SNE and quantified cell densities and marker co-expression patterns using binary cell counting. In addition to phenotyping immune cell types, their spatial localizations were analyzed. Neighborhood analysis was conducted using co-occurrence matrices to determine the number of times that a particular cell type is proximal to one another. Cell-to-cell spatial relationship was assessed by quantifying the Euclidean distances between individual cell types. These tools are being applied to specimens from an immunotherapy clinical trial to evaluate the dynamic changes in immune phenotype during the course of immune blockade therapy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".