CYS4
S. cerevisiae
cystathionine beta-synthase CYS4
What the model saw
Gene: CYS4 Organism: Saccharomyces cerevisiae Known functions: cystathionine beta-synthase CYS4. cystathionine beta-synthase activity. mRNA binding.
View unredacted entry
cystathionine beta-synthase CYS4. cystathionine beta-synthase activity. mRNA binding.
Solver output
CYS4 encodes cystathionine beta-synthase (CBS), which catalyzes the first committed step of the transsulfuration pathway, converting serine and homocysteine to cystathionine. This pathway is a critical route for producing cysteine and, downstream, glutathione — the cell's primary antioxidant buffer. In yeast, the transsulfuration pathway also feeds into hydrogen sulfide (H₂S) production, which has been shown to be a key mediator of caloric restriction-induced longevity. Activation of CBS/transsulfuration supports redox homeostasis and proteostasis by maintaining glutathione levels, and H₂S signaling intersects with TOR and nutrient-sensing pathways to extend lifespan. Loss of CYS4 function impairs cysteine and glutathione biosynthesis, increasing oxidative stress and reducing lifespan, consistent with a pro-longevity role for the wild-type gene.
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 predicted CYS4 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning focused on the beneficial roles of the transsulfuration pathway (glutathione production, H₂S signaling, redox homeostasis) and concluded that CYS4 loss would be harmful. However, in yeast, CYS4 deletion has actually been shown to extend lifespan, making it anti-longevity (i.e., the gene's normal activity limits lifespan). The model's mechanistic reasoning, while plausible on the surface, missed the actual experimental finding that CYS4 deletion extends yeast lifespan. The model was fairly confident (0.72) in the wrong direction. The transsulfuration pathway reasoning is partially relevant but leads to the wrong conclusion about the direction of effect.
Raw API responses
solver
{
"reasoning": "CYS4 encodes cystathionine beta-synthase (CBS), which catalyzes the first committed step of the transsulfuration pathway, converting serine and homocysteine to cystathionine. This pathway is a critical route for producing cysteine and, downstream, glutathione — the cell's primary antioxidant buffer. In yeast, the transsulfuration pathway also feeds into hydrogen sulfide (H₂S) production, which has been shown to be a key mediator of caloric restriction-induced longevity. Activation of CBS/transsulfuration supports redox homeostasis and proteostasis by maintaining glutathione levels, and H₂S signaling intersects with TOR and nutrient-sensing pathways to extend lifespan. Loss of CYS4 function impairs cysteine and glutathione biosynthesis, increasing oxidative stress and reducing lifespan, consistent with a pro-longevity role for the wild-type gene.",
"confidence": 0.72,
"key_pathways": [
"transsulfuration pathway",
"glutathione biosynthesis / redox homeostasis",
"hydrogen sulfide signaling / TOR nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted CYS4 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning focused on the beneficial roles of the transsulfuration pathway (glutathione production, H₂S signaling, redox homeostasis) and concluded that CYS4 loss would be harmful. However, in yeast, CYS4 deletion has actually been shown to extend lifespan, making it anti-longevity (i.e., the gene's normal activity limits lifespan). The model's mechanistic reasoning, while plausible on the surface, missed the actual experimental finding that CYS4 deletion extends yeast lifespan. The model was fairly confident (0.72) in the wrong direction. The transsulfuration pathway reasoning is partially relevant but leads to the wrong conclusion about the direction of effect.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}