Detecting rare copy number variants from Illumina genotyping arrays with the CamCNV pipeline: Segmentation of <i>z</i> ‐scores improves detection and reliability
Bibliographic record
Abstract
The intensities from genotyping array data can be used to detect copy number variants (CNVs) but a high level of noise in the data and overlap between different copy-number intensity distributions produces unreliable calls, particularly when only a few probes are covered by the CNV. We present a novel pipeline (CamCNV) with a series of steps to reduce noise and detect more reliably CNVs covering as few as three probes. The pipeline aims to detect rare CNVs (below 1% frequency) for association tests in large cohorts. The method uses the information from all samples to convert intensities to z-scores, thus adjusting for variance between probes. We tested the sensitivity of our pipeline by looking for known CNVs from the 1000 Genomes Project in our genotyping of 1000 Genomes samples. We also compared the CNV calls for 1661 pairs of genotyped replicate samples. At the chosen mean z-score cut-off, sensitivity to detect the 1000 Genomes CNVs was approximately 85% for deletions and 65% for duplications. From the replicates, we estimate the false discovery rate is controlled at ∼10% for deletions (falling to below 3% with more than five probes) and ∼28% for duplications. The pipeline demonstrates improved sensitivity when compared to calling with PennCNV, particularly for short deletions covering only a few probes. For each called CNV, the mean z-score is a useful metric for controlling the false discovery rate.
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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 | 0.005 | 0.016 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.012 | 0.005 |
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".