Evidence card: NCBI:GeneID:136271462

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
PRJEB18614	protein unc-13 homolog C-like	alexandrium_minutum_vs_heterocapsa_triquetra_diet	log2 fold change	0.3842	0.6142	0.6991	Study-level association; see design caveats
CGIG_HEAT_RNASEQ_PRJNA913164	protein unc-13 homolog C-like	30C_seawater_vs_20C_adult_ctenidium	log2 fold change	-0.8548	0.7259	0.4273	Study-level association; see design caveats
CGIG_MULTISTRESS_RNASEQ_PRJNA913164	protein unc-13 homolog C-like	30C_seawater_then_44C_emersion_6h_vs_20C_adult_ctenidium	log2 fold change	0.05501	0.7524	0.9721	Study-level association; see design caveats
PRJNA735889	protein unc-13 homolog C-like	ph_6.5_6.8_vs_ph_7.4_7.8_23d_juveniles	log2 fold change	0.1752	0.7683	0.9188 (nominal only)	Exploratory; tank clustering unmodeled
PRJNA1329250	protein unc-13 homolog C-like	oshv1_microvariant_challenge_vs_unchallenged_control	log2 fold change	0.575	0.3643	0.27	Study-level association; see design caveats
PRJNA856813	protein unc-13 homolog C-like	tire_leachate_high_vs_control_gill_day41	log2 fold change	5.403	1.02	0.0004473	Study-level association; see design caveats

CGIG_HAB_RNASEQ_PRJEB18614

Phenotype interpretation: A. minutum exposure is unfavorable. The publication reports remodelling of the gill cycling transcriptome (loss of oscillations, de novo oscillating transcripts, shortened periods) and toxin accumulation, not survival. AREE records the time-averaged gill transcriptional response to the toxic diet.

Biological replication: 24 pooled RNA-seq libraries in the primary analysis (12 per diet), each pooling gill RNA from 6 oysters. The original 26 libraries cover 13 time-matched pairs; both day 2 ZT 8.5 pools are excluded, leaving 12 pairs. There is no replication within a diet-by-time cell. Each diet used three tanks; sample_size counts analysed pools, not individual oysters or independent tanks.

Evidence classification: stress_response. Tissue: gill; life stage: adult.

Quality flags: raw_reanalysis;harmful_algal_bloom_response;time_averaged_over_diurnal_cycle;timepoint_blocked_contrast;sequencing_pool_partly_confounded.

Study limitations:

Each library was sequenced on two lanes; the lanes are technical duplicates of one library, not replicates. Only the lower-numbered lane of each pair is used (26 of the 52 deposited runs, 136.8 GB instead of about 274 GB). The unused run is named in each manifest row.
Reads come from two mirrors. 12 runs are the ENA FASTQs, checked against the manifest MD5s. The other 14, listed with NCBI’s size and MD5 in CGIG_HAB_RNASEQ_PRJEB18614_sra_locations.tsv, were converted from full NCBI .sra archives, and their read counts were checked against the manifest. They were moved to NCBI after ENA corrupted multi-connection transfers and then refused requests. Each library comes from one mirror only.
Both day 2 ZT 8.5 gill pools (control and A. minutum) carry adductor-muscle RNA from dissection and are excluded from the primary contrast; sample_size counts the 24 remaining pools. The all-26 fit is kept as a comparison.
Salmon detected one ENA library (control d1 ZT 12.5, ERR1758944) as ISF instead of the ISR expected for stranded TruSeq, so its read files are swapped relative to the rest. Library type is inferred per sample, so quantification is unaffected.
The primary contrast, ~ timepoint + condition, blocks on sampling time and uses 12 time-matched pools per diet after excluding the contaminated pair. The all-26 sensitivity model and publication use 13 per diet. The publication’s central finding is that A. minutum remodels the daily cycling of gill transcripts, so a diet effect averaged over time will miss, or dilute, effects confined to part of the cycle.
Diet is partly confounded with sequencing pool. The libraries were multiplexed into four pools, each on its own lane pair of one flowcell. Pool L003-L004 holds 6 A. minutum libraries and no controls, and pool L005-L006 holds 6 controls and 1 A. minutum library; pools L001-L002 and L007-L008 carry both diets. The sensitivity model with sequencing_pool as a covariate keeps the direction of 99.9% of the primary significant genes, including all 30 top genes, which also stay significant. Only 53.8% of genes overall stay significant, so the gene count depends on the model, but the direction does not.
Each diet used three tanks, but the publication does not say how the 6 oysters in each pool were drawn from them, so tank effects cannot be modelled.
Timepoint labels are Day and Zeitgeber time rounded down: d1_zt04 is Day 1 ZT 4.5 and d3_zt04 is Day 3 ZT 4.5, where ZT 0 is lights on. The methods list the same 13 times as the ArrayExpress SDRF.
Condition, time and lane come from the ArrayExpress E-MTAB-5345 SDRF (feeding condition, time and assay name), and every ENA sample alias matches its SDRF source name.
The publication aligned reads with STAR to the Ensembl Metazoa C. gigas genome and mitochondrial genome and tested diet with edgeR across the 13 times, reporting 740 differentially expressed transcripts at FDR < 0.01 (89.5% higher under A. minutum). The transcript list is not in the supplement, whose only table lists the 30 most significant cycling transcripts per class, so only the count and direction balance can be compared. AREE finds about 5,070 genes at FDR < 0.01, 59.6% higher under A. minutum. That is far more genes and a weaker up-bias than the published 740 transcripts (89.5% up), with a different aligner, count model and genome assembly.
The strongest A. minutum-higher genes form a lysosomal and endocytic programme (dipeptidyl peptidase 1, LAMP1, CD63, VPS4B, syntaxin-8) and include detoxification genes: the ABCB1 multidrug efflux pump, arylacetamide deacetylase and mitochondrial alternative oxidase.

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

Harmonized evidence. Processed input. Input SHA-256: 185cbdd6f509f43a79442fe2fd9137ea489711c4afe95d0f2a1a21c6c6b4762a.

CGIG_HEAT_RNASEQ_PRJNA913164

Phenotype interpretation: Mortality was elevated in the stress treatments relative to the control. AREE records the ctenidium transcriptional response to elevated seawater temperature, not survival per library.

Biological replication: 44 ctenidium libraries analysed, one oyster each (23 controls and 21 treated after QC exclusions), from 48 sequenced: 24 controls and 24 30 C, 12 diploid and 12 triploid in each arm. The 24 control libraries are shared with CGIG_MULTISTRESS_RNASEQ_PRJNA913164 (30 C followed by 44 C emersion).

Evidence classification: stress_response. Tissue: gill; life stage: adult.

Quality flags: raw_reanalysis;quantseq_3prime_tag_seq;ploidy_blocked_contrast;shared_control_group;dependence_group=PRJNA913164_20C_controls;temperature_response.

Study limitations:

The BioSamples carry no treatment or ploidy attribute. Both come from the description column of the authors’ NCBI submission sheet (github.com/mattgeorgephd/NOPP-gigas-ploidy-temp, 202107_EXP2/tag-seq/NCBI/attributes.tsv), matched to BioSample by isolate name; sample-name prefixes do not map one-to-one to groups.
The study has three arms that share one control group. AREE records each stressor against the 20 C controls as its own study (CGIG_MULTISTRESS_RNASEQ_PRJNA913164 (30 C followed by 44 C emersion) is the other), so the two records share their reference group and their effect estimates are correlated; they must not be treated as independent in a meta-analysis.
Diploids and triploids are pooled with ploidy as a blocking factor (~ ploidy + condition), so the effect is averaged over ploidy. The publication’s main finding is that triploids respond differently, especially to the multiple stressor; the ploidy-by-treatment interaction is reported in the quality-control summary, and ploidy-specific effects are not part of this record.
QuantSeq 3’ tag-seq yields about one read per transcript, so Salmon was run with –noLengthCorrection and DESeq2 used the counts without the tximport length offset (–tag-seq=yes). Library sizes are small (0.9-8.3 million reads), and isoform-level information is not recoverable.
The authors excluded eight libraries as outliers (D54, N56, X44, R53, M43, N54, X42, T62). AREE quantified all 72 and applied its own rule (median VST correlation below the median minus three robust SDs): seven of the authors’ eight fail it, D54 passes and is kept, and R62 and N57 also fail and are left out. The exclusions live in scripts/prepare_prjna913164_fastqs.py and remove one or two libraries from some ploidy-by-treatment cells.
The expressed-SNP replicate check (scripts/check_replicate_genotypes.py) could not be run: 3’ tags cover too little of the target transcripts (about 2,000 usable reads per library, even after poly-A and adapter trimming) to call allele frequencies. Each library is a single adult oyster according to the publication, so no pooling or resequencing is expected, but this was not verified genetically.

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

Harmonized evidence. Processed input. Input SHA-256: f77e0e6f5683b7fe006272a6c53cb16bb293cf3542164602272e155aa0f4bafb.

CGIG_MULTISTRESS_RNASEQ_PRJNA913164

Phenotype interpretation: Mortality after the multiple stressor was higher in triploids than diploids (36.4% versus 14.8%), with metabolic depression and reduced ctenidium Na/K-ATPase activity in triploids. AREE records the ctenidium transcriptional response averaged over ploidy, not survival per library.

Biological replication: 42 ctenidium libraries analysed, one oyster each (23 controls and 19 treated after QC exclusions), from 48 sequenced: 24 controls and 24 30 C + 44 C emersion, 12 diploid and 12 triploid in each arm. The 24 control libraries are shared with CGIG_HEAT_RNASEQ_PRJNA913164 (30 C seawater only).

Evidence classification: stress_response. Tissue: gill; life stage: adult.

Quality flags: raw_reanalysis;quantseq_3prime_tag_seq;ploidy_blocked_contrast;shared_control_group;dependence_group=PRJNA913164_20C_controls;multiple_stressor_response.

Study limitations:

The BioSamples carry no treatment or ploidy attribute. Both come from the description column of the authors’ NCBI submission sheet (github.com/mattgeorgephd/NOPP-gigas-ploidy-temp, 202107_EXP2/tag-seq/NCBI/attributes.tsv), matched to BioSample by isolate name; sample-name prefixes do not map one-to-one to groups.
The study has three arms that share one control group. AREE records each stressor against the 20 C controls as its own study (CGIG_HEAT_RNASEQ_PRJNA913164 (30 C seawater only) is the other), so the two records share their reference group and their effect estimates are correlated; they must not be treated as independent in a meta-analysis.
Diploids and triploids are pooled with ploidy as a blocking factor (~ ploidy + condition), so the effect is averaged over ploidy. The publication’s main finding is that triploids respond differently, especially to the multiple stressor; the ploidy-by-treatment interaction is reported in the quality-control summary, and ploidy-specific effects are not part of this record.
QuantSeq 3’ tag-seq yields about one read per transcript, so Salmon was run with –noLengthCorrection and DESeq2 used the counts without the tximport length offset (–tag-seq=yes). Library sizes are small (0.9-8.3 million reads), and isoform-level information is not recoverable.
The authors excluded eight libraries as outliers (D54, N56, X44, R53, M43, N54, X42, T62). AREE quantified all 72 and applied its own rule (median VST correlation below the median minus three robust SDs): seven of the authors’ eight fail it, D54 passes and is kept, and R62 and N57 also fail and are left out. The exclusions live in scripts/prepare_prjna913164_fastqs.py and remove one or two libraries from some ploidy-by-treatment cells.
The expressed-SNP replicate check (scripts/check_replicate_genotypes.py) could not be run: 3’ tags cover too little of the target transcripts (about 2,000 usable reads per library, even after poly-A and adapter trimming) to call allele frequencies. Each library is a single adult oyster according to the publication, so no pooling or resequencing is expected, but this was not verified genetically.

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

Harmonized evidence. Processed input. Input SHA-256: d2d6e4a07aa73594d97a4c9c4a593cace73fecddc5c11304a2bbef65277282d6.

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_OSHV1_RNASEQ_PRJNA1329250

Phenotype interpretation: Infection up-regulated antiviral defense transcripts, including RIG-I-like receptors and the interferon-like pathway, similarly in both lineages; AREE records molecular antiviral responsiveness, not an organism-level survival difference

Biological replication: 42 RNA-seq libraries: 12 controls (6 Midori, 6 Miyagi) and 30 OsHV-1 microvariant-challenged (15 Midori, 15 Miyagi, split across USA, Australia, and France viral strains at 5 libraries per lineage-strain cell)

Evidence classification: disease_associated. Tissue: whole_soft_tissue; life stage: spat.

Quality flags: raw_reanalysis;pathogen_challenge_response;lineage_balanced_contrast.

Study limitations:

This intake represents the molecular antiviral response to experimental OsHV-1 microvariant challenge, not a measured survival or organism-level disease-resistance difference between the two lineages.
Challenge dose, exposure duration, and time of sampling after inoculation are not recorded in the public SRA metadata, so exposure intensity and duration are unresolved.
The challenged and control arms are unequal in size (30 versus 12 libraries), but lineage is balanced within each arm and within every viral strain: 6 Midori and 6 Miyagi controls, and 5 of each lineage for each of the Australia, France, and USA strains. The lineage effect is therefore not confounded with infection status, and AREE blocks on lineage as ~ population + condition.
The publication contrasts the USA and Australia microvariant strains and reports no marked difference between them; the France-strain libraries are present in the BioProject and are pooled into the challenged arm of the AREE contrast rather than analyzed as a separate strain effect.
The BioProject carries no author-deposited processed expression matrix, so AREE has no published feature-level effect table to reconcile against.
Condition, lineage, and viral-strain assignments were reconstructed from NCBI BioSample attribute tags rather than from a supplementary sample table; the source metadata spells the Miyagi lineage ‘Myagi’, which AREE normalized.

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

Harmonized evidence. Processed input. Input SHA-256: 3beb15844b8040ff58c64acd452381f853bbbacb730cce2bf434b6ee05d41f2e.

CGIG_TIRELEACHATE_RNASEQ_PRJNA856813

Phenotype interpretation: The publication reports activation of energy metabolism and stress responses under leachate exposure, signs of microbiota dysbiosis at high concentrations, reduced sperm motility and oocyte transcriptional changes, but no significant ecophysiological change in adults and no effect on offspring growth, which it interprets as possible resilience. AREE records the gill transcriptional response, not a measured phenotype per library.

Biological replication: 12 day-41 gill libraries, one oyster each: 6 controls and 6 high-concentration leachate oysters.

Evidence classification: stress_response. Tissue: gill; life stage: adult.

Quality flags: raw_reanalysis;pollutant_exposure_response;shared_control_group;dependence_group=PRJNA856813_gill_controls;tire_leachate;fdr_lt_0.05.

Study limitations:

The publication is not open access and was not read in full; exposure concentrations, tank layout and the number of tanks per treatment are therefore not recorded here. If each treatment was held in a single tank, oyster-level replicates would not account for tank clustering.
Both AREE records from this study test against the same six day-41 gill control oysters, so they carry the dependence group PRJNA856813_gill_controls and count as one replication group.
AREE uses only the day-41 gill libraries of the control, high-concentration leachate and high-concentration tire microparticle groups. The deposited study also has low concentrations, a natural-particle control, digestive gland (day 44), gonad (day 44, four per group), time-zero baselines and 16S amplicon data, which are not used.
Groups come from the SRA sample names (D41_GI_<CTL | LEA_H | MR_H>_; D41 = day 41, GI = gill); the BioSamples record the tissue as gills. The ENA portal was unavailable when the study was staged, so the reads come from NCBI .sra archives checked against NCBI’s MD5s, and each converted FASTQ must match the SRA spot count.

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

Harmonized evidence. Processed input. Input SHA-256: 9f52f19bfaa110f7d5ba09e6d53e20073cd2ac0f540b2270c2aef8363909af42.

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.