Evidence card: NCBI:GeneID:117681484

Real public-study evidence. Association evidence only; not a validated biomarker.

How to interpret expression as evidence for resilience. Differential expression alone does not establish a resilience marker; higher expression does not necessarily mean greater resilience.

This feature was selected among up to ten displayed findings in at least one study. All available rows for it are shown below, including nonsignificant and exploratory results. Presence in multiple datasets does not establish independent replication: exposures, tissues, life stages, and phenotype meanings differ. No cross-study score or pooled effect is calculated.

Guide to effect sizes, uncertainty and gene descriptions.

Study-specific effects

Study / design	RefSeq description	Contrast	Effect scale	Effect	Standard error	Adjusted p-value	Interpretation
PRJNA735889	transforming growth factor-beta-induced protein ig-h3-like	ph_6.5_6.8_vs_ph_7.4_7.8_23d_juveniles	log2 fold change	0.5815	0.5411	0.5242 (nominal only)	Exploratory; tank clustering unmodeled
PRJNA826964	transforming growth factor-beta-induced protein ig-h3-like	ocean_acidification_vs_ambient_control	log2 fold change	-2.686	1.665	not available	Study-level association; see design caveats
CGIG_PESTO_F0_RNASEQ_PRJEB58194	transforming growth factor-beta-induced protein ig-h3-like	pesticide_mixture_0_48hpf_vs_control_F0_gastrula_dlarva	log2 fold change	0.2067	0.4223	0.87	Study-level association; see design caveats
CGIG_PESTO_F1DIRECT_RNASEQ_PRJEB58194	transforming growth factor-beta-induced protein ig-h3-like	pesticide_mixture_TE_vs_TT_F1_gastrula_pediveliger	log2 fold change	0.4681	0.2788	1	Study-level association; see design caveats
PRJNA694496	transforming growth factor-beta-induced protein ig-h3-like	thermotolerance_selected_vs_nonselected_control	log2 fold change	-4.293	0.1912	5.482e-108	Study-level association; see design caveats

CGIG_OA_RNASEQ_PRJNA735889

Phenotype interpretation: Lutier et al. report physiological tipping points at pHT 7.3-6.9 that coincide with a major reshuffling of the transcriptome and membrane lipids; AREE records the whole-animal transcriptional response below the tipping window relative to above it, not a measured tolerance phenotype

Biological replication: 50 oysters, one whole-animal library each: 25 control and 25 acidified, 5 per tank. A 51st library, 13Ebis, is a resequencing of oyster 13E and is not analysed. Each pH level is one tank, so oysters are replicates within tank and the 10 tanks are the replicates of the pH contrast.

Evidence classification: environmental_exposure. Tissue: whole_organism; life stage: juvenile.

Quality flags: raw_reanalysis;ocean_acidification_response;ph_band_contrast_tipping_window_excluded;no_ambient_ph_reference;one_tank_per_ph_level;gametogenesis_blocked_contrast;exploratory_tank_clustering_unmodeled.

Exploratory uncertainty: Tank clustering is unmodeled. Standard errors and adjusted p-values above are nominal only; this row is excluded from pooling and significance rewards.

Study limitations:

The study is a 15-level pH gradient (pHT 6.5-7.8, 76 libraries). AREE reduces it to a two-group contrast at the authors’ tipping-point window: the five tanks inside pHT 7.3-6.9 (tanks 1, 6, 4, 11 and 10; 25 libraries) are excluded and not downloaded. Effect sizes are therefore log2 fold changes between two pH bands, not slopes per pH unit, and they mix the response across five pH levels on each side.
There is no ambient-pH tank; the reference band (pHT 7.4-7.8) is itself below present-day coastal pH, so the contrast understates the full response to acidification.
Each pH level is a single tank, so tank and pH are confounded at the level of a single pH; with five tanks per band the band contrast has tank-level replication, but DESeq2 treats the 50 analysed oysters as independent and does not model tank. Standard errors, p-values and FDR values are exploratory and may overstate precision. A tank-aware reanalysis is required before inferential use; PCA and per-tank residual checks do not correct the error model.
Tank 15 is labelled ‘pHT 6.5 bis’ in BioSample: a second tank at pHT 6.5 alongside tank 9.
Library 13Ebis (SRR14803132) has a different index from 13E (SRR14803133) and about half its reads. The expressed-SNP check shows it is the same oyster (allele-frequency difference 0.026, below the 0.032 expected for one RNA resequenced; the next closest pair differs by 0.198), so it is kept in the manifest but left out of the analysis.
Male gametogenesis is unbalanced between bands: a spermatogenesis module is active in 11 of 25 control and 2 of 25 acidified oysters (Fisher p = 0.008), spread across all five control tanks, which suggests that low pH delays or suppresses the onset of spermatogenesis in 5-month-old juveniles. The primary model blocks on this call (~ gametogenesis + condition) so the evidence records a gametogenesis-adjusted association with pH, without establishing a direct causal response; the unadjusted model is kept as a sensitivity analysis. The call is a transcriptional proxy derived from the same data (scripts/score_prjna735889_gametogenesis.py), not a histological sex or maturation call, and with only two active acidified oysters the gametogenesis effect is estimated mostly from the control band.
Condition, tank and pH come from the NCBI BioSample title, treatment and growth_protocol attributes; every library is paired-end. ENA served the FASTQs at about 80 KB/s on 2026-10-02, so all 51 runs are taken from the NCBI Open Data mirror as .sra archives checked against the size and MD5 NCBI publishes (CGIG_OA_RNASEQ_PRJNA735889_sra_locations.tsv), and each converted FASTQ pair must match the manifest read count.

Provenance: Reference GCF_963853765.1 / RS_2024_06; mapping exact; workflow 0.1.0.

Harmonized evidence. Processed input. Input SHA-256: a8f7485ec9436cc334d22b6819d7137f37dccb753fa688700c49d264cb7c0dda.

CGIG_OA_RNASEQ_PRJNA826964

Phenotype interpretation: The BioProject title frames acidification as compromising energy management; AREE records the hepatopancreas transcriptional response to acidification, not a measured organism-level energetic or survival phenotype

Biological replication: 6 pooled RNA samples, one per arm at each of 7, 28 and 56 days, each sequenced as three libraries (18 libraries); the BioSample records call the libraries biological replicates, but their genotypes show each set of three is one pool of several oysters

Evidence classification: stress_response. Tissue: hepatopancreas; life stage: not_recorded.

Quality flags: raw_reanalysis;ocean_acidification_response;timepoint_blocked_contrast;pooled_rna_samples;possible_genetic_background_confound;deseq2_significance_unavailable.

Study limitations:

No publication is linked to the BioProject, and searches of PubMed, Europe PMC full text and Crossref on 2026-09-28 found none, so there are no published methods, results or effect tables to reconcile the reanalysis against.
The acidification intensity (target pH or pCO2), seawater carbonate chemistry, temperature and oyster size or age are not recorded in the public metadata, so exposure intensity and life stage are unresolved.
The treatment was probably CO2-driven acidification to pH 7.50. This is inferred, not documented: the same IOCAS group (L. Qiu and colleagues) ran C. gigas CO2 exposures at pH 7.50 sampled from 7 to 56 days (Wang et al. 2021, Ecotoxicol Environ Saf, doi:10.1016/j.ecoenv.2021.112235) and at pH 7.50 for 7 and 60 days (Wang et al. 2020, Sci Total Environ, doi:10.1016/j.scitotenv.2020.140177), and reported hepatopancreas responses to acidification over about two months (Zhang et al. 2021, J Oceanol Limnol, doi:10.1007/s00343-021-0462-x). None of these papers is linked to PRJNA826964, and the closed-access hepatopancreas paper, the most likely companion, has not been checked against it.
The primary AREE contrast compares the three acidified pools with the three control pools and blocks on sampling day (~ timepoint + condition); it estimates an acidification effect averaged over 7, 28 and 56 days rather than time-specific or acclimation effects, and it has only two residual degrees of freedom.
The three libraries per day-by-condition cell are technical replicates of one pooled RNA sample, not the independent biological replicates the BioSample attributes state. Expressed-SNP allele frequencies (scripts/check_replicate_genotypes.py, 4M read pairs per library) agree within a cell to within resequencing noise and show no single-animal genotype peaks, and within-cell expression dispersion is 2.7% BCV against 10.8-22.4% in the other AREE oyster studies. Treating the 18 libraries as replicates inflates significance roughly twelvefold, so the libraries are summed into 6 pools (–collapse-by=condition+timepoint).
Each pool is a different set of animals, and the acidified pools are genetically further from the controls (mean allele-frequency difference 0.24-0.31) than the control pools are from one another (0.085-0.19), so acidified and control oysters may come from different stocks or families. Several of the strongest effects are 4-6 log2 changes in transposon-derived genes (tigger, HARBI1), the pattern expected from presence-absence variation between genetic backgrounds, so part of the contrast may be genetic rather than an acidification response. The evidence is harmonized with every row flagged pooled_rna_samples and possible_genetic_background_confound, so scoring discounts it and evidence cards list the caveat; treat it as provisional acidification evidence until a design with shared genetic backgrounds confirms it.
Condition, sampling day and replicate were taken from NCBI BioSample treatment and replicate attributes and agree with the library names (C/O = control/acidified, followed by day and replicate).
The BioProject carries no author-deposited processed expression matrix.

Provenance: Reference GCF_963853765.1 / RS_2024_06; mapping exact; workflow 0.1.0.

Harmonized evidence. Processed input. Input SHA-256: 4a01845d837665c4e977190e7e9111a2d5a7bd3e5f38d89ca473276a96b26f2c.

CGIG_PESTO_F0_RNASEQ_PRJEB58194

Phenotype interpretation: The publication found no difference in embryo-larval abnormalities at 24 hpf, disturbed swimming, larger and heavier exposed larvae at some times, a lower epinephrine-induced metamorphosis rate and higher field survival, and differential expression of developmental genes (Hox orthologues, cell-cycle regulators) in gastrulae. AREE records the transcriptional response averaged over two stages.

Biological replication: 36 libraries: 18 control and 18 exposed, nine per stage (gastrula, D larva), labelled with group digits 1-3 and replicate letters A-F.

Evidence classification: environmental_exposure. Tissue: whole_organism; life stage: embryo_larva.

Quality flags: raw_reanalysis;pollutant_exposure_response;pesticide_mixture;pooled_libraries;stage_blocked_contrast;direct_exposure.

Study limitations:

One control D-larva sample title (BT2Ed) is attached to two runs (ERR10659105, ERR10659106); both are kept with the run accession appended to the replicate, and the expressed-SNP check tests whether they are one sample.
The exposure is a mixture of 18 pesticides and metals at environmentally relevant concentration (nominal sum 2.85 ug/L; measured 3.74 ug/L in F0) during embryo-larval development (0-48 h post fertilization) at the Ifremer Bouin hatchery.
Each library is presumably a pool of many embryos or larvae; pool size, culture vessels and the meaning of the F0 group digits (1-3) are not recorded in the public metadata, and pools were checked with the expressed-SNP test (scripts/check_replicate_genotypes.py) before analysis.
All runs come from NCBI .sra archives checked against NCBI’s MD5s (11 F0 runs have no ENA FASTQ), with read counts checked against the NCBI spot counts on conversion.
The study also deposited F0 pediveligers (sampled after exposure) and F1 offspring exposed in both generations (EE); AREE does not use them.

Provenance: Reference GCF_963853765.1 / RS_2024_06; mapping exact; workflow 0.1.0.

Harmonized evidence. Processed input. Input SHA-256: 5eb3fa1130b516be240eecebcd8c88a5b405a6739f99d273764f3054814af5bb.

CGIG_PESTO_F1DIRECT_RNASEQ_PRJEB58194

Phenotype interpretation: The publication found that the parents’ exposure shaped the offspring phenotype more than direct exposure did; offspring of exposed parents had lower epinephrine-induced metamorphosis and field survival. AREE records the transcriptional response to direct exposure averaged over two stages.

Biological replication: 12 libraries: 6 TT and 6 TE, three per stage.

Evidence classification: environmental_exposure. Tissue: whole_organism; life stage: embryo_larva.

Quality flags: raw_reanalysis;pollutant_exposure_response;pesticide_mixture;pooled_libraries;stage_blocked_contrast;shared_control_group;dependence_group=PRJEB58194_F1_TT;direct_exposure.

Study limitations:

The two F1 records (direct exposure TE and parental exposure ET) test against the same six TT libraries, so they carry the dependence group PRJEB58194_F1_TT; only the direct-exposure record is harmonized.
The exposure is a mixture of 18 pesticides and metals at environmentally relevant concentration (nominal sum 2.85 ug/L; measured 3.74 ug/L in F0) during embryo-larval development (0-48 h post fertilization) at the Ifremer Bouin hatchery.
Each library is presumably a pool of many embryos or larvae; pool size, culture vessels and the meaning of the F0 group digits (1-3) are not recorded in the public metadata, and pools were checked with the expressed-SNP test (scripts/check_replicate_genotypes.py) before analysis.
All runs come from NCBI .sra archives checked against NCBI’s MD5s (11 F0 runs have no ENA FASTQ), with read counts checked against the NCBI spot counts on conversion.
The study also deposited F0 pediveligers (sampled after exposure) and F1 offspring exposed in both generations (EE); AREE does not use them.

Provenance: Reference GCF_963853765.1 / RS_2024_06; mapping exact; workflow 0.1.0.

Harmonized evidence. Processed input. Input SHA-256: eeb95c68cdb8cacd7c256a0616f24042aaa54da88a33682cf82f476119e25b62.

CGIG_THERMOTOL_RNASEQ_PRJNA694496

Phenotype interpretation: Selected population had higher post-heat-shock survival (78.05% versus 66.34%) and field summer survival (73% versus 62%)

Biological replication: RNA-seq: 3 selected-population and 3 control-population larval libraries; number of larvae pooled per library was not reported

Evidence classification: resilience_associated. Tissue: whole_larva; life stage: umbo_larva.

Quality flags: raw_reanalysis;qc_reviewed;population_selection_association;constitutive_expression;selected_A_pc2_displacement;sensitivity_direction_robust;fdr_lt_0.05.

Study limitations:

The RNA-seq comparison is constitutive selected-versus-control expression at the larval stage, not an acute heat-versus-control contrast.
Thermotolerance survival was measured in related later-stage cohorts rather than the RNA-sequenced larval pools.
The publication reports 4,764 DEGs but does not provide the complete feature-level effect, p-value, or standard-error table in its supplementary archive.
The publication describes three replicates per group but does not report how many larvae were pooled into each RNA-seq library.
All six runs share one BioSample record, and its tissue field says gill despite the publication consistently describing whole umbo larvae; AREE follows the publication for tissue and records the discrepancy.
The source genome assembly and differential-expression software/threshold are not reported clearly enough for exact reproduction; AREE used GCF_963853765.1/RS_2024_06, so these results are a current-reference reanalysis rather than an exact reconstruction of the publication pipeline.
Selected_B and selected_C have lower Salmon mapping rates than the other libraries, and selected_A is displaced on PC2; sensitivity analysis supports the primary effect directions, but these patterns remain QC caveats.

Provenance: Reference GCF_963853765.1 / RS_2024_06; mapping exact; workflow 0.1.0.

Harmonized evidence. Processed input. Input SHA-256: 636f73eb2b9094e50a8c3c3213792513bff4e26fc203a607471190188445b6a3.

Next validation step

Independent biological replication with matched exposure and measured phenotype, an appropriate experimental-unit model, and targeted validation in the relevant tissue and life stage.