Automated Analysis of Multidimensional Flow Cytometry Data Improves Diagnostic Accuracy Between Mantle Cell Lymphoma and Small Lymphocytic Lymphoma
Bibliographic record
Abstract
Mantle cell lymphoma (MCL) and small lymphocytic lymphoma (SLL) exhibit similar but distinct immunophenotypic profiles. Many cases can be diagnosed readily by flow cytometry (FCM) alone; however, ambiguous cases are frequently encountered and necessitate additional studies, including immunohistochemical staining for cyclin D1 and fluorescence in situ hybridization for IgH-CCND1 rearrangement. To determine if greater diagnostic accuracy could be achieved from FCM data alone, we developed an unbiased, machine-based algorithm to identify features that best distinguish between the 2 diseases. By applying conventional diagnostic criteria to the flow cytometry data, we were able to assign 28 of 44 (64%) MCL and 48 of 70 (69%) SLL cases correctly. In contrast, we were able to assign all 44 (100%) MCL and 68 of 70 (97%) SLL cases correctly using a novel set of criteria, as identified by our automated approach. The most discriminating feature was the CD20/CD23 mean fluorescence intensity ratio, and we found unexpectedly that inclusion of FMC7 expression in the diagnostic algorithm actually reduced its accuracy. This study demonstrates that computational methods can be used on existing clinical FCM data to improve diagnostic accuracy and suggests similar computational approaches could be used to identify novel prognostic markers and perhaps subdivide existing or define new diagnostic entities.
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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 | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| 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".