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Novel Site Explorer (/novel/{gene})

A different question from the Genome View. That page asks "did the model get this gene's known sites right?" This one asks the discovery question:

For this gene, what are the top candidate sites that appear in no annotation at all?

That is a ranked list, and per-gene precision@k is literally the metric M3 is evaluated on — so the page has the same shape as the evaluation.

What a row shows

Column Meaning
Rank / M3 score the meta model's ranking of this candidate
Base score, base rank what the base model gave the same position
GT/AG the splice dinucleotide, strand-aware
Evidence badges ENCODE long-read support, held-out disease anchors

The GT/AG column is a live correctness check, not decoration. Every row landing on the canonical dinucleotide for its strand and site type means the coordinate handling is right. It caught a real bug during development: offsets reasoned from first principles scored 0.00, and the convention had to be recovered empirically.

Evidence is deliberately independent

Badges come from ENCODE long-read transcripts (D1) and held-out disease anchors (D2). Neither is what M3 trained on.

SpliceVault is deliberately not shown

SpliceVault (positives_pooled) is M3's training pool. Displaying it as supporting evidence would be circular — it would say "the model found what it was trained on."

The servable universe

Serving is restricted to the 4,956 genes on held-out chromosomes ⅓/5/7/9 — the ones M3 never trained on. 165 of them carry a novel disease anchor.

This is a feature. You cannot accidentally demo a training gene. Familiar genes like BRCA1, TP53 and UNC13A are on training chromosomes and are not available here; the page loads and shows an inline message naming the universe.

A good first gene: DHX29

M3 rank Type M3 prob Base prob Base rank GT/AG Long-read
1 acceptor 1.0000 0.0000 284 AG ✓ 8 biosamples
2 donor 1.0000 0.0008 13 GT —
3 donor 0.9999 0.0395 2 GT ✓ 1

The base model buries a real, long-read-confirmed, SF3B1-mutant cryptic site at rank 284 with probability ≈ 0. M3 ranks it first.

ATP6V1A is a good second (anchor at M3 rank 5 vs base rank 132). TPR works but is a weaker illustration — base already ranks its anchors 3rd and 4th.

How to read a low base score

A near-zero base score is the point, not a failure. These are cryptic sites: low base score is what makes them cryptic. The gain here is re-ranking, not new evidence.

Equally, a top-ranked candidate is a candidate. Across the held-out set M3 recovers about 79% of disease cryptics in the top 20 per gene versus 51% for base, so expect roughly 1–2 of any top-5 to be long-read confirmed. It is a triage tool, not a truth oracle.

Status

M3 is registered status: research, not promoted. It is deliberately kept out of the genome-view overlay dropdown and the metrics dashboard: it is scored by per-gene precision@k on independent truth, not by the PR-AUC those surfaces expect, and its 7-channel input would fail against the 9-channel cache they use.

Full results: M3 — Novel Splice Sites.