ash-2
C. elegans
B30.2/SPRY domain-containing protein;Set1/Ash2 histone methyltransferase complex subunit ash-2
What the model saw
Gene: ash-2 Organism: Caenorhabditis elegans Known functions: B30.2/SPRY domain-containing protein;Set1/Ash2 histone methyltransferase complex subunit ash-2. transcription cis-regulatory region binding.
View unredacted entry
B30.2/SPRY domain-containing protein;Set1/Ash2 histone methyltransferase complex subunit ash-2. transcription cis-regulatory region binding.
Solver output
ash-2 encodes a subunit of the Set1/Ash2 histone methyltransferase complex, which catalyzes H3K4 methylation (H3K4me3), an active transcription mark. In C. elegans, H3K4me3 levels are regulated across generations and influence lifespan; loss of ash-2 reduces H3K4me3 and has been shown to extend lifespan, suggesting that the normal (wild-type) function of ash-2 — promoting H3K4 trimethylation — is associated with a shorter lifespan. However, ash-2 also supports transcriptional programs necessary for stress resistance and proteostasis. The dominant finding in the literature is that ash-2 activity (via the COMPASS-like complex) maintains a youthful epigenome in early life but its sustained activity in aging promotes age-associated transcriptional dysregulation, making its normal function net anti-longevity. Its B30.2/SPRY domain and cis-regulatory binding activity further support its role in transcriptional co-activation within this methyltransferase complex.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly identified the mechanism (ash-2 as a Set1/Ash2 histone methyltransferase complex subunit that promotes H3K4me3, and that loss of ash-2 extends lifespan), but then predicted the wrong longevity influence. The model's reasoning actually correctly describes ash-2 as anti-longevity (loss of function extends lifespan = wild-type function shortens lifespan = anti-longevity), but then contradictorily assigned "pro_longevity" as the final prediction. The model seemed confused in its final classification despite correctly reasoning through the mechanism. The ground truth is "anti_longevity," but the model predicted "pro_longevity." This is a case where the mechanistic reasoning was correct but the final answer was wrong — essentially the model contradicted its own reasoning in the final classification.
Raw API responses
solver
{
"reasoning": "ash-2 encodes a subunit of the Set1/Ash2 histone methyltransferase complex, which catalyzes H3K4 methylation (H3K4me3), an active transcription mark. In C. elegans, H3K4me3 levels are regulated across generations and influence lifespan; loss of ash-2 reduces H3K4me3 and has been shown to extend lifespan, suggesting that the normal (wild-type) function of ash-2 — promoting H3K4 trimethylation — is associated with a shorter lifespan. However, ash-2 also supports transcriptional programs necessary for stress resistance and proteostasis. The dominant finding in the literature is that ash-2 activity (via the COMPASS-like complex) maintains a youthful epigenome in early life but its sustained activity in aging promotes age-associated transcriptional dysregulation, making its normal function net anti-longevity. Its B30.2/SPRY domain and cis-regulatory binding activity further support its role in transcriptional co-activation within this methyltransferase complex.",
"confidence": 0.72,
"key_pathways": [
"H3K4 trimethylation via Set1/COMPASS complex",
"Epigenetic regulation of transcription",
"Histone methyltransferase complex assembly"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified the mechanism (ash-2 as a Set1/Ash2 histone methyltransferase complex subunit that promotes H3K4me3, and that loss of ash-2 extends lifespan), but then predicted the wrong longevity influence. The model's reasoning actually correctly describes ash-2 as anti-longevity (loss of function extends lifespan = wild-type function shortens lifespan = anti-longevity), but then contradictorily assigned \"pro_longevity\" as the final prediction. The model seemed confused in its final classification despite correctly reasoning through the mechanism. The ground truth is \"anti_longevity,\" but the model predicted \"pro_longevity.\" This is a case where the mechanistic reasoning was correct but the final answer was wrong — essentially the model contradicted its own reasoning in the final classification.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}