Using backend API at: http://localhost:8001
Using LLM provider: openai
Backend API test response: 42

== COMPLEX QUERY ==
We are interested in finding activators of DHTKD1, find all of them and list their mechanism of working
Starting iterative deepening MCTS with 7 depth iterations

== DEPTH ITERATION 1/7 ==
Running MCTS with 10 iterations from node Query Root
Iteration 1 stats:
  Total nodes explored: 2
  Maximum depth reached: 1
  Average depth: 1.00
  Maximum information gain: 0.80

== DEPTH ITERATION 2/7 ==
Running MCTS with 10 iterations from node dhtkd1
Running MCTS with 10 iterations from node Query Root
Iteration 2 stats:
  Total nodes explored: 12
  Maximum depth reached: 2
  Average depth: 2.00
  Maximum information gain: 1.60

== DEPTH ITERATION 3/7 ==
Running MCTS with 10 iterations from node dhtkd1 ko cells
Running MCTS with 10 iterations from node knock-out of dhtkd1 alters mitochondrial respiration and function, and may represent a novel pathway in cardiometabolic disease risk
Running MCTS with 10 iterations from node os
Iteration 3 stats:
  Total nodes explored: 33
  Maximum depth reached: 3
  Average depth: 2.75
  Maximum information gain: 2.40

== DEPTH ITERATION 4/7 ==
Running MCTS with 10 iterations from node 4
Running MCTS with 10 iterations from node 4
Running MCTS with 10 iterations from node 4
Iteration 4 stats:
  Total nodes explored: 63
  Maximum depth reached: 4
  Average depth: 3.42
  Maximum information gain: 3.20

== DEPTH ITERATION 5/7 ==
Running MCTS with 10 iterations from node secondary antibodies
Running MCTS with 10 iterations from node dhtkd1 mutations
Running MCTS with 10 iterations from node glutaric aciduria type i
Iteration 5 stats:
  Total nodes explored: 73
  Maximum depth reached: 5
  Average depth: 3.65
  Maximum information gain: 4.00

== DEPTH ITERATION 6/7 ==
Running MCTS with 10 iterations from node cells
Running MCTS with 10 iterations from node charcot-marie-tooth disease type 2
Running MCTS with 10 iterations from node 2-aminoadipic and 2-oxoadipic aciduria
Iteration 6 stats:
  Total nodes explored: 98
  Maximum depth reached: 6
  Average depth: 4.30
  Maximum information gain: 4.80

== DEPTH ITERATION 7/7 ==
Running MCTS with 10 iterations from node huh7 cells
Running MCTS with 10 iterations from node sk-hep1 cells
Running MCTS with 10 iterations from node bl21/de3 cells
Iteration 7 stats:
  Total nodes explored: 116
  Maximum depth reached: 7
  Average depth: 4.74
  Maximum information gain: 5.60

== TREE STATISTICS ==
total_nodes: 116
leaf_nodes: 99
internal_nodes: 17
max_depth: 7
avg_depth: 4.74
max_branching: 10
avg_branching: 8.43
max_info_gain: 5.60
avg_info_gain: 3.63

== IDENTIFIED MULTI-LEVEL EXPLORATION PATHS ==
Path 1: (Query Root)--(explore)-->(dhtkd1)
Path 3: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1)
Path 4: (Query Root)--(explore)-->(dhtkd1), (knock-out of dhtkd1 alters mitochondrial respiration and function, and may represent a novel pathway in cardiometabolic disease risk)--(SYNTACTIC_CONTAINS)-->(dhtkd1)
Path 5: (Query Root)--(explore)-->(dhtkd1), (dhtkd1)--(has_negligible_activity_with)-->(os)
Path 6: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1), (dhtkd1 ko cells)--(BELONGS_TO_CLUSTER)-->(4 {description: This cluster focuses on the consequences of the DHTKD1 gene mutation, particularly the (c.2185G>A, p.G729R) variant, and its role in metabolic disorders. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), which is crucial in the L-lysine degradation pathway within mitochondria. This enzyme complex is important for mitochondrial biogenesis and function maintenance. The G729R substitution significantly decreases catalytic efficiency for NADH production and impacts the overall activity of the OADHc. This mutation is linked to disorders such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD) and may contribute to mitochondrial dysfunctions associated with conditions like Charcot-Marie-Tooth disease type 2Q and eosinophilic esophagitis. The studies utilize methods like hydrogen-deuterium exchange and chemical cross-linking mass spectrometry to assess protein-protein interactions, highlighting how these mutations can disrupt functional interactions within the OADHc. The findings underscore DHTKD1's role in metabolic phenotypes and implications for cardiometabolic disease risks.})
Path 9: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1), (dhtkd1 ko cells)--(BELONGS_TO_CLUSTER)-->(4 {description: This cluster focuses on the consequences of the DHTKD1 gene mutation, particularly the (c.2185G>A, p.G729R) variant, and its role in metabolic disorders. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), which is crucial in the L-lysine degradation pathway within mitochondria. This enzyme complex is important for mitochondrial biogenesis and function maintenance. The G729R substitution significantly decreases catalytic efficiency for NADH production and impacts the overall activity of the OADHc. This mutation is linked to disorders such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD) and may contribute to mitochondrial dysfunctions associated with conditions like Charcot-Marie-Tooth disease type 2Q and eosinophilic esophagitis. The studies utilize methods like hydrogen-deuterium exchange and chemical cross-linking mass spectrometry to assess protein-protein interactions, highlighting how these mutations can disrupt functional interactions within the OADHc. The findings underscore DHTKD1's role in metabolic phenotypes and implications for cardiometabolic disease risks.}), secondary antibodies--(BELONGS_TO_CLUSTER)-->4
Path 10: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1), (dhtkd1 ko cells)--(BELONGS_TO_CLUSTER)-->(4 {description: This cluster focuses on the consequences of the DHTKD1 gene mutation, particularly the (c.2185G>A, p.G729R) variant, and its role in metabolic disorders. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), which is crucial in the L-lysine degradation pathway within mitochondria. This enzyme complex is important for mitochondrial biogenesis and function maintenance. The G729R substitution significantly decreases catalytic efficiency for NADH production and impacts the overall activity of the OADHc. This mutation is linked to disorders such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD) and may contribute to mitochondrial dysfunctions associated with conditions like Charcot-Marie-Tooth disease type 2Q and eosinophilic esophagitis. The studies utilize methods like hydrogen-deuterium exchange and chemical cross-linking mass spectrometry to assess protein-protein interactions, highlighting how these mutations can disrupt functional interactions within the OADHc. The findings underscore DHTKD1's role in metabolic phenotypes and implications for cardiometabolic disease risks.}), dhtkd1 mutations--(BELONGS_TO_CLUSTER)-->4
Path 11: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1), (dhtkd1 ko cells)--(BELONGS_TO_CLUSTER)-->(4 {description: This cluster focuses on the consequences of the DHTKD1 gene mutation, particularly the (c.2185G>A, p.G729R) variant, and its role in metabolic disorders. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), which is crucial in the L-lysine degradation pathway within mitochondria. This enzyme complex is important for mitochondrial biogenesis and function maintenance. The G729R substitution significantly decreases catalytic efficiency for NADH production and impacts the overall activity of the OADHc. This mutation is linked to disorders such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD) and may contribute to mitochondrial dysfunctions associated with conditions like Charcot-Marie-Tooth disease type 2Q and eosinophilic esophagitis. The studies utilize methods like hydrogen-deuterium exchange and chemical cross-linking mass spectrometry to assess protein-protein interactions, highlighting how these mutations can disrupt functional interactions within the OADHc. The findings underscore DHTKD1's role in metabolic phenotypes and implications for cardiometabolic disease risks.}), glutaric aciduria type i--(BELONGS_TO_CLUSTER)-->4
Path 12: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1), (dhtkd1 ko cells)--(BELONGS_TO_CLUSTER)-->(4 {description: This cluster focuses on the consequences of the DHTKD1 gene mutation, particularly the (c.2185G>A, p.G729R) variant, and its role in metabolic disorders. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), which is crucial in the L-lysine degradation pathway within mitochondria. This enzyme complex is important for mitochondrial biogenesis and function maintenance. The G729R substitution significantly decreases catalytic efficiency for NADH production and impacts the overall activity of the OADHc. This mutation is linked to disorders such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD) and may contribute to mitochondrial dysfunctions associated with conditions like Charcot-Marie-Tooth disease type 2Q and eosinophilic esophagitis. The studies utilize methods like hydrogen-deuterium exchange and chemical cross-linking mass spectrometry to assess protein-protein interactions, highlighting how these mutations can disrupt functional interactions within the OADHc. The findings underscore DHTKD1's role in metabolic phenotypes and implications for cardiometabolic disease risks.}), secondary antibodies--(BELONGS_TO_CLUSTER)-->4, (cells)--(incubated with)-->(secondary antibodies)
Path 13: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1), (dhtkd1 ko cells)--(BELONGS_TO_CLUSTER)-->(4 {description: This cluster focuses on the consequences of the DHTKD1 gene mutation, particularly the (c.2185G>A, p.G729R) variant, and its role in metabolic disorders. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), which is crucial in the L-lysine degradation pathway within mitochondria. This enzyme complex is important for mitochondrial biogenesis and function maintenance. The G729R substitution significantly decreases catalytic efficiency for NADH production and impacts the overall activity of the OADHc. This mutation is linked to disorders such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD) and may contribute to mitochondrial dysfunctions associated with conditions like Charcot-Marie-Tooth disease type 2Q and eosinophilic esophagitis. The studies utilize methods like hydrogen-deuterium exchange and chemical cross-linking mass spectrometry to assess protein-protein interactions, highlighting how these mutations can disrupt functional interactions within the OADHc. The findings underscore DHTKD1's role in metabolic phenotypes and implications for cardiometabolic disease risks.}), dhtkd1 mutations--(BELONGS_TO_CLUSTER)-->4, (dhtkd1 mutations)--(cause)-->(charcot-marie-tooth disease type 2)
Path 14: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1), (dhtkd1 ko cells)--(BELONGS_TO_CLUSTER)-->(4 {description: This cluster focuses on the consequences of the DHTKD1 gene mutation, particularly the (c.2185G>A, p.G729R) variant, and its role in metabolic disorders. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), which is crucial in the L-lysine degradation pathway within mitochondria. This enzyme complex is important for mitochondrial biogenesis and function maintenance. The G729R substitution significantly decreases catalytic efficiency for NADH production and impacts the overall activity of the OADHc. This mutation is linked to disorders such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD) and may contribute to mitochondrial dysfunctions associated with conditions like Charcot-Marie-Tooth disease type 2Q and eosinophilic esophagitis. The studies utilize methods like hydrogen-deuterium exchange and chemical cross-linking mass spectrometry to assess protein-protein interactions, highlighting how these mutations can disrupt functional interactions within the OADHc. The findings underscore DHTKD1's role in metabolic phenotypes and implications for cardiometabolic disease risks.}), dhtkd1 mutations--(BELONGS_TO_CLUSTER)-->4, (dhtkd1 mutations)--(cause)-->(2-aminoadipic and 2-oxoadipic aciduria)
Path 15: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1), (dhtkd1 ko cells)--(BELONGS_TO_CLUSTER)-->(4 {description: This cluster focuses on the consequences of the DHTKD1 gene mutation, particularly the (c.2185G>A, p.G729R) variant, and its role in metabolic disorders. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), which is crucial in the L-lysine degradation pathway within mitochondria. This enzyme complex is important for mitochondrial biogenesis and function maintenance. The G729R substitution significantly decreases catalytic efficiency for NADH production and impacts the overall activity of the OADHc. This mutation is linked to disorders such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD) and may contribute to mitochondrial dysfunctions associated with conditions like Charcot-Marie-Tooth disease type 2Q and eosinophilic esophagitis. The studies utilize methods like hydrogen-deuterium exchange and chemical cross-linking mass spectrometry to assess protein-protein interactions, highlighting how these mutations can disrupt functional interactions within the OADHc. The findings underscore DHTKD1's role in metabolic phenotypes and implications for cardiometabolic disease risks.}), secondary antibodies--(BELONGS_TO_CLUSTER)-->4, (cells)--(incubated with)-->(secondary antibodies), (huh7 cells)--(SYNTACTIC_CONTAINS)-->(cells)
Path 16: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1), (dhtkd1 ko cells)--(BELONGS_TO_CLUSTER)-->(4 {description: This cluster focuses on the consequences of the DHTKD1 gene mutation, particularly the (c.2185G>A, p.G729R) variant, and its role in metabolic disorders. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), which is crucial in the L-lysine degradation pathway within mitochondria. This enzyme complex is important for mitochondrial biogenesis and function maintenance. The G729R substitution significantly decreases catalytic efficiency for NADH production and impacts the overall activity of the OADHc. This mutation is linked to disorders such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD) and may contribute to mitochondrial dysfunctions associated with conditions like Charcot-Marie-Tooth disease type 2Q and eosinophilic esophagitis. The studies utilize methods like hydrogen-deuterium exchange and chemical cross-linking mass spectrometry to assess protein-protein interactions, highlighting how these mutations can disrupt functional interactions within the OADHc. The findings underscore DHTKD1's role in metabolic phenotypes and implications for cardiometabolic disease risks.}), secondary antibodies--(BELONGS_TO_CLUSTER)-->4, (cells)--(incubated with)-->(secondary antibodies), (sk-hep1 cells)--(SYNTACTIC_CONTAINS)-->(cells)
Path 17: (Query Root)--(explore)-->(dhtkd1), (dhtkd1 ko cells)--(SYNTACTIC_CONTAINS)-->(dhtkd1), (dhtkd1 ko cells)--(BELONGS_TO_CLUSTER)-->(4 {description: This cluster focuses on the consequences of the DHTKD1 gene mutation, particularly the (c.2185G>A, p.G729R) variant, and its role in metabolic disorders. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), which is crucial in the L-lysine degradation pathway within mitochondria. This enzyme complex is important for mitochondrial biogenesis and function maintenance. The G729R substitution significantly decreases catalytic efficiency for NADH production and impacts the overall activity of the OADHc. This mutation is linked to disorders such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD) and may contribute to mitochondrial dysfunctions associated with conditions like Charcot-Marie-Tooth disease type 2Q and eosinophilic esophagitis. The studies utilize methods like hydrogen-deuterium exchange and chemical cross-linking mass spectrometry to assess protein-protein interactions, highlighting how these mutations can disrupt functional interactions within the OADHc. The findings underscore DHTKD1's role in metabolic phenotypes and implications for cardiometabolic disease risks.}), secondary antibodies--(BELONGS_TO_CLUSTER)-->4, (cells)--(incubated with)-->(secondary antibodies), (bl21/de3 cells)--(SYNTACTIC_CONTAINS)-->(cells)

== PATH-BASED ANSWER==
The main focus regarding DHTKD1 in the explored knowledge graph paths revolves around various mutations and their implications on metabolic disorders and mitochondrial functions. However, there is no specific mention of direct pharmaceutical or biochemical activators of the DHTKD1 enzyme in the paths provided. Below, I offer a synthesis of the available information:

1. **Path 1 to Path 17**: These paths primarily address the role of DHTKD1 and its mutations, especially the (c.2185G>A, p.G729R) variant. DHTKD1 encodes for the 2-oxoadipate dehydrogenase complex (OADHc), crucial for the L-lysine degradation pathway within mitochondria, and is involved in mitochondrial biogenesis and function maintenance. The mutation decreases catalytic efficiency for NADH production, affecting overall OADHc activity. These pathways point to the involvement of DHTKD1 in conditions such as 𝛂-aminoadipic and 𝛂-ketoadipic aciduria (AMOXAD), Charcot-Marie-Tooth disease type 2Q, and eosinophilic esophagitis (Paths 6, 9, 10, 11, and 13-17).

2. **Mechanisms Involved**: DHTKD1 mutations result in mitochondrial dysfunctions due to impaired protein interactions within the OADHc, contributing to metabolic anomalies and disease risks (Path 6-17 description cluster).

3. **Trade-offs and Interactions**: The mutations in DHTKD1, by affecting NADH production, have broad implications for mitochondrial energy metabolism which may lead to metabolic diseases (Path 4).

4. **Implications for Specific Patient Populations**: The DHTKD1 mutations are linked with specific metabolic disorders, likely affecting patient populations with rare genetic diseases described above, impacting their metabolic profiles and associated disease risks (Paths 6-17 description cluster).

5. **Overall Safety and Efficacy Considerations**: No specific activators or safety-related data regarding pharmaceutical interventions targeting DHTKD1 are detailed in the paths. The discussions are more focused on genetic and biochemical implications of mutations.

6. **Clinical Trial Data**: There is no mention of clinical trial data within the paths.

While the explored paths do not provide direct information about activators of DHTKD1, they detail the importance of DHTKD1 in mitochondrial function and metabolic processes. Further research might require delving into biochemical studies or clinical trials aimed at modulating mitochondrial enzymes or addressing genetic deficiencies linked to DHTKD1 for potential therapeutic strategies.

== REFERENCES ==
quines_pdf (Page: 11)
FEBS Letters - 2013 - Xu - DHTKD1 is essential for mitochondrial biogenesis and function maintenance_pdf (Page: 1, 2, 4, 5, 6)
PMC3516599_pdf (Page: 1, 2, 5)
J of Inher Metab Disea - 2015 - Hagen - Genetic basis of alpha‐aminoadipic and alpha‐ketoadipic aciduria_pdf (Page: 1, 3, 4, 5, 6, 7)
PMC7278340_pdf (Page: 1, 2, 3, 15, 16, 17)
PMC8774751_pdf (Page: 1, 2, 4, 8, 14)
zbc8078_pdf (Page: 1, 2, 3, 15, 16, 17)
PMC7890914_pdf (Page: 1, 2, 3, 4, 9, 11)
PMC8414881_pdf (Page: 1, 3, 4, 6, 7, 8)
genes-13-00084_pdf (Page: 1)
PMC9134613_pdf (Page: 3, 4)
PMC5398483_pdf (Page: 17)
PMC6193743_pdf (Page: 6, 7, 8, 9, 13, 15, 21, 23)