Fetal and embryonic targets: source requirements

Update (2026-10-26): the uniform quantitative proposal now imports all genes from E-MTAB-9388 as developmental TPM evidence. Brachyury qualifies quantitatively; the source is one early embryo, so later-fetal and independent-embryo coverage described below remains outstanding.

Assessment date: 26 October 2026. This is a source and evidence-gap assessment, not an ingestion-complete developmental atlas. The biological membership set now includes TBXT, AFP, GPC3, CLDN6 and SALL4 through reviewed gene-specific primary evidence, with adult-expression concerns preserved.

Brachyury is TBXT (historical symbol T), ENSG00000164458. The current reference-bound expression screen places it in Neither / Antibody. It should be evaluated as a developmental/lineage target with explicit adult-expression review, rather than assuming that an embryonic label proves adult absence.

Why brachyury needs additional adult coverage

A primary human study assessed gene expression in 60 and IHC in 56 nucleus pulposus specimens and reported brachyury in adult cells across age and degeneration groups. This is a concrete adult compartment often absent from routine bulk-normal panels. Other studies report age-dependent findings, so specimen state and antibody specificity must be reconciled rather than reducing the evidence to a single presence/absence flag. Richardson et al., 2017, Tang et al., 2016.

Chordoma clinical experience also needs careful interpretation. The randomized GI-6301 vaccine/radiotherapy trial had one partial response in each arm and did not establish the proposed benefit. A later single-arm BN-Brachyury/radiotherapy study reported two partial responses among 26 evaluable patients and missed its predefined response goal. These observations establish clinical experience, not general efficacy or tolerability of all TBXT-targeting modalities. Randomized phase II study, Cote et al., 2024.

Data to add

Evidence layer Primary sources What to retain and why
Early embryonic lineage Tyser human gastrulation atlas Cell counts and annotations, exact embryo/stage and anatomical lineage. Early axial mesoderm/notochord programs can be missed by later fetal organ sampling. A single-embryo dataset cannot establish population prevalence.
Early organogenesis Human embryo atlas, 2023; post-gastrulation spatial atlas, 2026 Embryo, stage, dissected region, spatial coordinates and cell-state labels. Spatial context distinguishes lineage-localized expression from a broad whole-embryo signal. Confirm access and licensing for each actual matrix before registration.
Multi-organ fetal expression Cao et al. fetal atlas and DESCARTES data portal Raw/processed expression and donor-level metadata across 15 organs. Useful for a general developmental nomination source; it does not cover every early transient lineage or every developmental stage.
Musculoskeletal development Human embryonic skeletal atlas RNA and spatial evidence for joint/cartilage and related developmental states. Include adult disc/nucleus-pulposus studies separately; fetal skeletal coverage cannot stand in for adult absence.
Adult normal and rare cells Existing pinned HPA/GTEx/cell evidence, plus the adult nucleus-pulposus primary studies above Donor, age, degeneration/inflammation, precise disc compartment, assay identity and protein controls. Broaden other candidates to their relevant adult residual lineages and regenerative states.
Tumor recurrence and lineage Patient chordoma bulk/single-cell cohorts, including GSE239531, linked to its primary study Malignant-cell assignment, patient denominator, site, treatment status, tumor subtype and assay. Cell-line dependency data are useful but cannot substitute for patient occurrence or normal-cell coverage.
Protein and presented antigen Gene-specific IHC/proteomics and HLA Ligand Atlas, with its primary methods paper Keep gene, isoform/protein, peptide and HLA identities separate. A missing mass-spectrometry observation is detection-limited; normal RNA and protein do not directly quantify peptide presentation.
Clinical evidence Primary trial reports and trial registries Modality, product, antigen identity, HLA where applicable, tumor response denominators, adverse events and attribution. Separate registration, immune responses, objective tumor response and toxicity findings.

The existing normal-cell source registry already contains staged fetal corneal data from GSE155683, alongside its adult data. That is a useful stage-aware ingestion precedent, not general embryonic or fetal coverage. Its fetal rows must not enter adult-normal exclusions by accident.

Integration contract

Each downloaded artifact needs an accession/version, public source URL, license, content hash and immutable source receipt. Keep native counts, normalized values and their actual units; the current human HPA nTPM thresholds do not transfer directly to sparse single-cell counts, CP10K, TPM or other species.

Every observation needs an exact gene ID and annotation release, transcript/ protein identity where measured, species, donor/embryo, independent specimen, anatomy, cell type, assay, developmental stage and physiological state. Record whether age means post-conception weeks, gestational weeks or another convention; retain the original label and uncertainty. In-vitro embryo models, organoids, adult stem cells and mouse atlases must be separate source classes, not human in-vivo observations.

Summaries must expose the independent donor denominator, per-donor distribution, detected-cell fractions and technical coverage. Do not treat thousands of cells from one embryo as thousands of independent donors. Missing cell types, stages, normal organs or non-detection remain explicit gaps. Maternal, placental and fetal compartments require distinct labels.

Developmental nomination should be a separate evidence field beside adult normal-expression results and tumor recurrence. It can nominate TBXT, AFP, CLDN6 and other independently supported targets for review without silently overriding their adult findings. In the current policy AFP has a normal-RNA exclusion and CLDN6 a high-normal-RNA exclusion; a developmental label alone does not revise those measurements.

Register and checksum the gastrulation, organogenesis and DESCARTES inputs; retain their original donor/stage annotations. Build a reference-bound TBXT case report joining embryonic lineage, adult disc, patient chordoma and clinical records. Audit gene-specific reagent/isoform identity and measured adult normal contexts to refine risk and developmental coverage for the biological members. Apply the same source contract to other developmental nominees. No new developmental classification cutoff or automatic fetal-expression admission is established by this assessment.