Propagation by Homology

IN_PROGRESS PIPELINEEVALUATION

Propagation by Homology

Bottom line: many GO annotations reach a gene by transfer from another gene
product: an ortholog (ISO), a sequence a curator judged similar (ISS/ISA), a
PANTHER family node placed by a PAINT curator (IBA), or an electronic pipeline
that does the same automatically (Ensembl Compara, TreeGrafter, InterPro2GO).
A transfer can go wrong in three places: the donor annotation can be weak or
stale, the orthology or tree relation can point to the wrong gene, or the term
can describe a context that does not carry over to the target. This page indexes
the projects that review these transfers method by method, and a propagation
browser that shows each transferred annotation as donor, intermediate and target
beside the gene review's verdict. We built it so that reviewers record where each
defect sits, and so that a fix can go to the mapping, node or pipeline that
produced it, where one change corrects every affected gene. In the statistics
generated on 2026-09-26, reviewers had judged 34,253 of 34,265 propagated
annotations and flagged 13% as REMOVE, MARK_AS_OVER_ANNOTATED or MODIFY: 9% of
PAINT IBA, 20% of Ensembl Compara and 28% of TreeGrafter annotations. Of the
4,232 ISO annotations, 383 rest on a donor that no longer carries the term, and
3,000 (71%) add an assertion with no related IBA on the target.

Browse all propagated annotations — one row per
transferred GOA annotation, read as donor(s) → intermediate → target, with what
the donor carries today, what else the target already carries, and the gene
review's verdict. Filter by method, donor or target species, donor support,
review action, or failure mode; the URL records the selection.
Browser guide ·
Current statistics

The three parts of every transfer

Every propagated annotation has the same shape, whatever the method:

Part ISO / ISS / ISA IBA (PAINT) Ensembl Compara (IEA)
Donor Gene product(s) in WITH/FROM, carrying an experimental annotation Seed genes with experimental annotations, listed in WITH/FROM Ortholog with an experimental annotation
Intermediate The orthology or similarity call (Alliance, HCOP, curator) The PANTHER ancestral node (PTN…) where a curator placed the function The Compara ortholog relation (≥40% identity)
Target The annotated gene Every descendant of the node The annotated gene

A review therefore asks three separate questions, and a failure can sit in any one
of them:

  1. Is the donor annotation sound? Does the donor still carry the term, with
    experimental support, from a paper about that gene?
  2. Is the relation the right one? One-to-one ortholog, a paralog, one of an
    expanded family, or a node that the target should not descend from.
  3. Is this term safe to move? Conserved activity versus tissue, lineage,
    compartment, or regulatory context that does not transfer.

The shared vocabulary for recording the answer is the
ISO/IBA failure taxonomy (review.propagation_review).

Projects

Project Method Question
ISO review ISO (GO_REF:0000119, 0000096, 0000121) Which orthology transfers are sound, which are stale or transfers-of-transfers, and what ISO adds on top of IBA.
IBA annotation quality IBA (GO_REF:0000033) Whether the PAINT node placement fits the target: paralog subfamilies, lost sub-activities, lineage mismatches.
PAINT no-IBA genes IBA gaps Human genes with no IBA — missing PAINT coverage or genuinely lineage-specific function.
TreeGrafter IEA (GO_REF:0000118) Automatic placement onto PANTHER trees and inheritance of PAINT annotations.
eggNOG-mapper eggNOG orthology (not in GOA) How the union of every ortholog's GO terms holds up against reviews, with and without the query's own species, and on non-model genomes.
Ortholog conjecture Orthologs vs paralogs Whether orthologs retain function more than paralogs in the reviewed corpus.
InterPro2GO IEA (GO_REF:0000002) Family- and domain-signature transfers and where they over-reach.
NCBIFam / CDD Family HMMs What NCBI family models add or mis-assign.

Status and follow-ups

The propagation browser and current statistics are built and committed from a
2026-09-26 donor cache. Component projects continue to move independently: PAINT
no-IBA reviews, the IBA corpus re-review, InterPro2GO and NCBIFAM/CDD mapping
proposals, TreeGrafter recomputation, and the ortholog-conjecture pilot each
need their own refresh or curator-facing handoff before the next umbrella
snapshot. The cross-project tracker is
#4095.

Methods covered by the browser

Method definitions follow the GO_REF descriptions in
go-site gorefs.yaml.

Evidence · reference Method Donor → target
ISO · GO_REF:0000119 Alliance automated transfer human experimental → mouse ortholog
ISO · GO_REF:0000096 Alliance automated transfer mouse ↔ rat orthologs
ISO · GO_REF:0000121 RGD transfer (HCOP/Alliance orthologs) other mammals → rat
ISO · GO_REF:0000008 MGI curated orthology human or rat → mouse
ISS/ISA/ISO · GO_REF:0000024 Curator judgment of similarity any → any (mostly UniProt)
ISA · GO_REF:0000113 TFClass DNA-binding-domain classification human DbTF family
IBA · GO_REF:0000033 PAINT seed genes → PANTHER node → descendants
IEA · GO_REF:0000107 Ensembl Compara experimental → orthologs (≥40% identity)
IEA · GO_REF:0000118 TreeGrafter PAINT node → grafted sequence
IEA · GO_REF:0000120 Combined IEA, rows with a Compara or PANTHER component as above

The browser also includes ISO/ISS/ISA rows that cite a paper instead of a GO_REF.
ISM (sequence-model predictors such as AtSubP) is not homology transfer and is not
included.

Rebuilding

just refresh-propagation-sources   # network: donor identities (UniProt), donor GO (QuickGO), GO closure
just deploy-propagation-browser    # offline: app/propagation/
just propagation-stats             # offline: HOMOLOGY_PROPAGATION/propagation-stats.md

The donor cache lives in HOMOLOGY_PROPAGATION/data/ and is committed, so the
browser and statistics rebuild offline and reproducibly; refresh it when GOA
files are re-fetched.

All projects in this collection

Generated from project frontmatter (collections: [HOMOLOGY_PROPAGATION]).

ProjectMaturityTags
Conserved-function recovery: can GO annotation find a function every genome has?IN_PROGRESSEVALUATION
eggNOG-mapper EvaluationIN_PROGRESSEVALUATION, PIPELINE
Fungal PAINT Family ReviewsIN_PROGRESS
IBA Annotation Quality ProjectMATUREPIPELINE, FLAGSHIP
Inferred from Sequence Orthology (ISO) Evidence Code ReviewIN_PROGRESSPIPELINE, EVALUATION
InterPro Mapping Review ProjectIN_PROGRESSPIPELINE
MitoTOL: Mitochondrial Proteomes Across the Tree of LifeIN_PROGRESSBIOLOGY_DOMAIN
NCBIFAM / CDD → GO Contribution & Gap ProjectIN_PROGRESSPIPELINE
Ortholog Conjecture ProjectSCOPINGEVALUATION
PAINT Human No-IBA Gene Review ProjectIN_PROGRESSPIPELINE, FLAGSHIP
PseudoCAP annotation review: P. aeruginosa seeds of PAINT IBAsIN_PROGRESSBIOLOGY_DOMAIN, PIPELINE
Re-examining the RAR misannotation study (Wei et al. 2020)IN_PROGRESSEVALUATION
Taxon Pathway VarianceIN_PROGRESSBIOLOGY_DOMAIN
TreeGrafter Inference EvaluationMATUREEVALUATION, PIPELINE