A Flexible and Powerful Bayesian Hierarchical Model for ChIP–Chip Experiments
Bibliographic record
Abstract
Chromatin-immunoprecipitation microarrays (ChIP-chip) that enable researchers to identify regions of a given genome that are bound by specific DNA-binding proteins present new challenges for statistical analysis due to the large number of probes, the high noise-to-signal ratio, and the spatial dependence between probes. We propose a method called BAC (Bayesian analysis of ChIP-chip) to detect transcription factor bound regions, which incorporate the dependence between probes while making little assumptions about the bound regions (e.g., length). BAC is robust to probe outliers with an exchangeable prior for the variances, which allows different variances for the probes but still shrink extreme empirical variances. Parameter estimation is carried out using Markov chain Monte Carlo and inference is based on the joint distribution of the parameters. Bound regions are detected using posterior probabilities computed from the joint posterior distribution of neighboring probes. We show that these posterior probabilities are well calibrated and can be used to obtain an estimate of the false discovery rate. The method is illustrated using two publicly available ChIP-chip data sets containing 18 experimentally validated regions. We compare our method to four other baseline and commonly used techniques, namely, the Wilcoxon's rank sum test, TileMap, HGMM, and MAT. We found BAC and HGMM to perform best at detecting validated regions. However, HGMM appears to be very sensitive to probe outliers compared to BAC. In addition, we present a simulation study, which shows that BAC is more powerful than the other four techniques under various simulation scenarios while being robust to model misspecification.
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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 | 0.009 | 0.017 |
| Meta-epidemiology (narrow) | 0.001 | 0.002 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.006 | 0.002 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".