Computational analysis optimizes the flow cytometric evaluation for lymphoma
Bibliographic record
Abstract
Background: Although many clinical laboratories are adopting higher color flow cytometric assays, the approach to optimizing panel design and data analysis is often traditional and subjective. In order to address the question "What is the best flow cytometric strategy to reliably distinguish germinal center B-cell lymphoma (GC-L) from lymphoid hyperplasia (GC-H)?" we applied a computational tool that identifies target populations correlated with a desired outcome, in this case diagnosis. Design: Cases of GC-H and GC-L with a germinal center phenotype, evaluated by flow cytometric immunophenotyping using CD45, CD20, kappa, lambda, CD19, CD5, CD10, CD38, were analyzed with flowType and RchyOptimyx to construct cellular hierarchies that best distinguished the two diagnostic groups. Results: The population CD5-CD19+CD10+CD38- had the highest predictive power. Manual reanalysis confirmed significantly higher CD10+/CD38-B-cells in GC-L (median 12.44%, range 0.74 - 63.29, n=52) than GC-H (median 0.24%, 0.03 - 4.49, n=48, p=0.0001), but was not entirely specific. Difficulties encountered using this computational approach included the presence of CD10+ granulocytes, continuously variable B-cell expression of CD38, more variable intensity antigen staining in GC-L and inability to assess the contribution of light chain restriction. Conclusion: Computational analysis with construction of cellular hierarchies related to diagnosis helped guide manual analysis of high dimensional flow cytometric data. This approach highlighted the diagnostic utility of CD38 expression in the evaluation of B-cells with a CD10+ GC phenotype. In contrast to computational analysis of non-neoplastic cell populations, evaluation of neoplastic cells must be able to take into consideration increased variability in antigen expression. © 2013 Clinical Cytometry Society.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".