30374e3fc3390902c35bb463510567f1b6f7a96e lrnassar Wed Apr 22 13:44:44 2026 -0700 PrimateAI-3D: clarify origin of the 0.821 threshold per Max. refs #37274 Description previously juxtaposed the paper's 0.821 clinical threshold with the 75/25 benign/pathogenic split in a way that implied the two were related. Per Max on the ticket: the 0.821 threshold comes from Gao et al. 2023 Fig. 5A (calibrated against de novo missense excess in a clinical cohort, n=7,238 pathogenic calls), and the "prediction" column values are Illumina's own calls — not a simple application of the 0.821 threshold (some variants below it are labeled pathogenic and vice versa). diff --git src/hg/makeDb/trackDb/human/primateAi.html src/hg/makeDb/trackDb/human/primateAi.html index efbefed0947..7f4ea570c65 100644 --- src/hg/makeDb/trackDb/human/primateAi.html +++ src/hg/makeDb/trackDb/human/primateAi.html @@ -24,39 +24,46 @@ position sometimes produce the same amino acid change (codon degeneracy), each item is labeled by default with its <b>nucleotide change</b> (e.g. <code>C>T</code>) rather than its amino acid change. The label can be switched to the amino acid change via the "Label fields" control in the Track Settings. </p> <p> Hovering over a variant shows: </p> <ul> <li><b>Var</b> — the nucleotide substitution on the + strand (reference > alternate)</li> <li><b>AA</b> — the resulting amino acid change (single-letter reference > alternate)</li> <li><b>Score</b> — the raw PrimateAI-3D pathogenicity score (0–1). - The authors suggest a clinical threshold of 0.821 for distinguishing - pathogenic from benign missense variants.</li> + The authors suggest a clinical threshold of <b>0.821</b> for + distinguishing pathogenic from benign missense variants. This + threshold was calibrated against a subset of annotated mutations + in Gao et al. 2023 (Fig. 5A), chosen so that the number of + PrimateAI-3D pathogenic calls matched the observed excess of de + novo missense mutations in a clinical cohort (n = 7,238).</li> <li><b>Perc</b> — the percentile rank of the raw score across all scored variants (0–1). The track score field (0–1000) is this value scaled by 1000.</li> <li><b>Pred</b> — Illumina's binary call: <span style="color:#0000c8">benign</span> or - <span style="color:#c80000">pathogenic</span>. In the track as - distributed, about 75% of variants are benign and 25% are pathogenic.</li> + <span style="color:#c80000">pathogenic</span>, as provided in the + source file. About 75% of variants in the track are benign and 25% + pathogenic. Note that this call is <em>not</em> a simple application + of the 0.821 raw-score threshold — some variants with raw + scores below 0.821 are labeled pathogenic and vice versa.</li> </ul> <p> Items can be filtered by prediction (benign/pathogenic), by raw PrimateAI-3D score, or by percentile. </p> <h2>Data Access</h2> <p> Due to the data license, the Table Browser, Data Integrator, and the REST API's <code>getData</code> endpoint are disabled for this track. The source data can be downloaded from the <a href="https://primateai3d.basespace.illumina.com/" target="_blank">PrimateAI-3D website</a> (requires registration). The primate variant database is available at <a href="https://primad.basespace.illumina.com/" target="_blank">PrimAD</a>.