Predictability of human differential gene expression
Bibliographic record
Abstract
Differential expression (DE) is commonly used to explore molecular mechanisms of biological conditions. While many studies report significant results between their groups of interest, the degree to which results are specific to the question at hand is not generally assessed, potentially leading to inaccurate interpretation. This could be particularly problematic for metaanalysis where replicability across datasets is taken as strong evidence for the existence of a specific, biologically relevant signal, but which instead may arise from recurrence of generic processes. To address this, we developed an approach to predict DE based on an analysis of over 600 studies. A predictor based on empirical prior probability of DE performs very well at this task (mean area under the receiver operating characteristic curve, ∼0.8), indicating that a large fraction of DE hit lists are nonspecific. In contrast, predictors based on attributes such as gene function, mutation rates, or network features perform poorly. Genes associated with sex, the extracellular matrix, the immune system, and stress responses are prominent within the “DE prior.” In a series of control studies, we show that these patterns reflect shared biology rather than technical artifacts or ascertainment biases. Finally, we demonstrate the application of the DE prior to data interpretation in three use cases: ( i ) breast cancer subtyping, ( ii ) single-cell genomics of pancreatic islet cells, and ( iii ) metaanalysis of lung adenocarcinoma and renal transplant rejection transcriptomics. In all cases, we find hallmarks of generic DE, highlighting the need for nuanced interpretation of gene phenotypic associations.
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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 | 0.014 | 0.043 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".