Inference of transcriptional regulation from STARR-seq data
Bibliographic record
Abstract
One of the primary regulatory processes in cells is transcription, during which RNA polymerase II (Pol-II) transcribes DNA into RNA. The binding of Pol-II to its site is regulated through interactions with transcription factors (TFs) that bind to DNA at enhancer cis-regulatory elements. Measuring the enhancer activity of large libraries of distinct DNA sequences is now possible using massively parallel reporter assays (MPRAs), and computational methods have been developed to identify the dominant statistical patterns of TF binding within these large datasets. Such methods are global in their approach and may overlook important regulatory sites that function only within the local context. Here we introduce a method for inferring functional regulatory sites (their number, location, and width) within an enhancer sequence based on measurements of its transcriptional activity from an MPRA method such as STARR-seq. The model is based on a mean-field thermodynamic description of Pol-II binding that includes interactions with bound TFs. Our method applied to simulated STARR-seq data for a variety of enhancer architectures shows how data quality impacts the inference and also how it can find local regulatory sites that may be missed in a global approach. We also apply the method to recently measured STARR-seq data on androgen receptor (AR) bound sequences, a TF that plays an important role in the regulation of prostate cancer. The method identifies key regulatory sites within these sequences, which are found to overlap with binding sites of known coregulators of AR.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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 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".