Machine learning approach for discrimination of genotypes based on bright-field cellular images
Bibliographic record
Abstract
Morphological profiling is a combination of established optical microscopes and cutting-edge machine vision technologies, which stacks up successful applications in high-throughput phenotyping. One major question is how much information can be extracted from an image to identify genetic differences between cells. While fluorescent microscopy images of specific organelles have been broadly used for single-cell profiling, the potential ability of bright-field (BF) microscopy images of label-free cells remains to be tested. Here, we examine whether single-gene perturbation can be discriminated based on BF images of label-free cells using a machine learning approach. We acquired hundreds of BF images of single-gene mutant cells, quantified single-cell profiles consisting of texture features of cellular regions, and constructed a machine learning model to discriminate mutant cells from wild-type cells. Interestingly, the mutants were successfully discriminated from the wild type (area under the receiver operating characteristic curve = 0.773). The features that contributed to the discrimination were identified, and they included those related to the morphology of structures that appeared within cellular regions. Furthermore, functionally close gene pairs showed similar feature profiles of the mutant cells. Our study reveals that single-gene mutant cells can be discriminated from wild-type cells based on BF images, suggesting the potential as a useful tool for mutant cell profiling.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".