Connections between ETV6-Modulated Genes: Identification of Shared Features
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Bibliographic record
Abstract
Accumulating genetic and functional evidence point to ETV6 as being the tumour suppressor gene targeted by the deletions at chromosome 12p12-13 found in various cancers, particularly childhood leukemia. ETV6 is a ubiquitously expressed transcription factor (TF) of the ETS family with very few known targeted genes. We recently compiled a list of 87 ETV6-modulated genes that can be classified into a number of subgroups based on their coordinated expression patterns. In the present report, we hypothesized that genes presenting a similar profile of modulation could also share biological features, promoter sequence similarities and/or, common transcription factor binding sites (TFBSs). Using an exploratory approach based on hierarchical clustering of expression data, Gene Ontology (GO) terms, sequence similarity and evolutionary conserved putative TFBSs, we found that many genes presenting a similar expression profile also share biological features and/or conserved predicted TFBSs but rarely show detectable promoter sequence similarities. We also calculated the proportion of ETV6-modulated genes that have any conserved TFBSs of the Jaspar database in their regulatory sequence and compared these proportions to those calculated for two other gene lists, ETV6 non-modulated and ETS-regulated. We found that the NF-kB, c-REL and p65 TFBSs, which all bind TFs of the REL class, were under-represented among the ETV6-modulated genes compared to the ETV6-non-modulated genes, while the Broad-complex 1 TFBS appeared to be over-represented. NF-Y and Chop/cEBP TFBSs were over-represented in the promoters of ETV6-modulated genes compared to ETS-regulated genes. These analyses will help direct further studies intending to understand the role of ETV6 as a transcriptional regulator and aid in constructing the ETV6-regulatory gene network.
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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 it