6e61d3349b36cbcc01500c1483cc7bfbc141d9ea
lrnassar
  Wed Apr 22 13:47:33 2026 -0700
PrimateAI-3D: tighten 0.821 threshold wording per the paper. refs #37274

Confirmed against Gao 2023 (PMC10713091): the calibration cohort is the
Deciphering Developmental Disorders (DDD) neurodevelopmental cohort, not
ClinVar. The cutoff was chosen so that the count of pathogenic calls
(n=7,238) matched the excess of de novo missense mutations above the
trinucleotide background expectation in that cohort.

diff --git src/hg/makeDb/trackDb/human/primateAi.html src/hg/makeDb/trackDb/human/primateAi.html
index 7f4ea570c65..67f715c352b 100644
--- src/hg/makeDb/trackDb/human/primateAi.html
+++ src/hg/makeDb/trackDb/human/primateAi.html
@@ -25,35 +25,37 @@
 each item is labeled by default with its <b>nucleotide change</b> (e.g. <code>C&gt;T</code>)
 rather than its amino acid change. The label can be switched to the amino acid
 change via the &quot;Label fields&quot; control in the Track Settings.
 </p>
 
 <p>
 Hovering over a variant shows:
 </p>
 <ul>
   <li><b>Var</b> &mdash; the nucleotide substitution on the + strand
       (reference&nbsp;&gt;&nbsp;alternate)</li>
   <li><b>AA</b> &mdash; the resulting amino acid change
       (single-letter reference&nbsp;&gt;&nbsp;alternate)</li>
   <li><b>Score</b> &mdash; the raw PrimateAI-3D pathogenicity score (0&ndash;1).
       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&nbsp;=&nbsp;7,238).</li>
+      distinguishing pathogenic from benign missense variants. In Gao
+      et al. 2023 (Fig. 5A) this threshold was derived from the
+      Deciphering Developmental Disorders (DDD) neurodevelopmental
+      cohort: the cutoff was chosen so that the number of variants
+      scored as pathogenic (n&nbsp;=&nbsp;7,238) matched the observed
+      excess of de novo missense mutations above the trinucleotide
+      background expectation in that cohort.</li>
   <li><b>Perc</b> &mdash; the percentile rank of the raw score across all
       scored variants (0&ndash;1). The track score field (0&ndash;1000) is this
       value scaled by 1000.</li>
   <li><b>Pred</b> &mdash; Illumina&apos;s binary call:
       <span style="color:#0000c8">benign</span> or
       <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 &mdash; 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.