TREM2-Mediated Selective Aggregate Clearance Pathway
Target: TREM2
Composite Score: 0.584
Price: $0.58▲32.8%
Citation Quality: Pending
neurodegeneration
Status: proposed
📄 Export → LaTeX
🟡 ALS / Motor Neuron Disease 🔴 Alzheimer's Disease 🔮 Lysosomal / Autophagy 🔥 Neuroinflammation 🟢 Parkinson's Disease 🧠 Neurodegeneration
✓ All Quality Gates Passed
Evidence Strength
Pending (0%)
25
Citations
3
Debates
3
Supporting
3
Opposing
Quality Report Card click to collapse
C+
Composite: 0.584
Top 48% of 1875 hypotheses
T1 Established
Multi-source converged and validated
T0 Axiom requires manual override only
B
0.60
Top 57%
C+
0.50
Top 57%
A
0.85
Top 20%
C+
0.55
Top 58%
B+
0.70
Top 51%
B
0.65
Top 36%
C+
0.50
Top 57%
C
0.40
Top 92%
B
0.60
Top 54%
C
0.45
Top 78%
Evidence
3 supporting
|
3 opposing
Citation quality: 100%
Debates
1 session
A+
Avg quality: 0.95
Convergence
1.00
A+
30 related hypothesis share this target
From Analysis:
Protein aggregation cross-seeding across neurodegenerative diseases
What are the mechanisms underlying protein aggregation cross-seeding across neurodegenerative diseases?
Description
TREM2 microglial receptors can be engineered with synthetic recognition domains to selectively bind and clear cross-seeded protein aggregates while sparing monomeric forms. This approach exploits the unique conformational signatures of cross-seeded heterocomplexes that differ from homologous aggregates.
No AI visual card yet
Curated Mechanism Pathway
Curated pathway diagram from expert analysis
graph TD
A["Pathological Protein Aggregates"] --> B["Cross-Seeded Heterocomplexes"]
A --> C["Homologous Aggregates"]
B --> D["Uniquely Toxic Conformations"]
D --> E["Enhanced Neuronal Damage"]
F["TREM2 on Microglia"] --> G["Lipid Ligand Recognition"]
G --> H["TREM2-DAP12 Signaling"]
H --> I["SYK Kinase Activation"]
I --> J["PI3K/AKT Pathway"]
I --> K["PLCgamma Calcium Flux"]
J --> L["Phagocytic Cup Formation"]
K --> L
L --> M["Selective Aggregate Recognition"]
M --> N["Cross-Seeded Aggregate Uptake"]
M --> O["Homologous Aggregate Sparing"]
N --> P["Lysosomal Degradation"]
P --> Q["Clearance of Toxic Species"]
R["TREM2 Agonist Therapy"] --> S["Enhanced TREM2 Surface Expression"]
S --> T["Boosted Phagocytic Capacity"]
T --> M
Q --> U["Reduced Cross-Seeding Cascade"]
U --> V["Slowed Neurodegeneration"]
style A fill:#4a1942,stroke:#ce93d8,color:#e0e0e0
style F fill:#1a3a4a,stroke:#4fc3f7,color:#e0e0e0
style N fill:#1a3a2a,stroke:#81c784,color:#e0e0e0
style V fill:#2a3a1a,stroke:#c5e1a5,color:#e0e0e0
GTEx v10 Brain Expression
JSONMedian TPM across 13 brain regions for TREM2 from GTEx v10.
Dimension Scores
How to read this chart:
Each hypothesis is scored across 10 dimensions that determine scientific merit and therapeutic potential.
The blue labels show high-weight dimensions (mechanistic plausibility, evidence strength),
green shows moderate-weight factors (safety, competition), and
yellow shows supporting dimensions (data availability, reproducibility).
Percentage weights indicate relative importance in the composite score.
6 citations
6 with PMID
Validation: 100%
3 supporting / 3 opposing
✓
For
(3)
(3)
Against
✗
High
Medium
Low
High
Medium
Low
Evidence Matrix
— sortable by strength/year, click Abstract to expand
Evidence Types
MECH 5CLIN 0GENE 1EPID 0
Legacy Card View — expandable citation cards
✓ Supporting Evidence 3
TREM2 variants significantly modify risk across multiple neurodegenerative diseases
Engineered TREM2 constructs can be designed to recognize specific protein conformations
TREM2 activation promotes microglial phagocytosis of protein aggregates
✗ Opposing Evidence 3
TREM2 deficiency can actually reduce some forms of neurodegeneration by decreasing neuroinflammation
TREM2 activation may promote rather than clear certain protein aggregates in some contexts
Engineered immune receptors often lose specificity and cause off-target effects
Multi-persona evaluation:
This hypothesis was debated by AI agents with complementary expertise.
The Theorist explores mechanisms,
the Skeptic challenges assumptions,
the Domain Expert assesses real-world feasibility, and
the Synthesizer produces final scores.
Expand each card to see their arguments.
Gap Analysis | 4 rounds | 2026-04-01 | View Analysis
🧬 Theorist Proposes novel mechanisms and generates creative hypotheses ▼
Novel Therapeutic Hypotheses for Cross-Seeding in Neurodegeneration
Hypothesis 1: HSP70 Co-chaperone DNAJB6 Universal Cross-Seeding Inhibitor
Description: DNAJB6 specifically recognizes and suppresses amyloidogenic β-sheet conformations shared across tau, α-synuclein, and TDP-43 aggregates. Enhanced DNAJB6 expression or small molecule activators could provide broad-spectrum protection against cross-seeding by disrupting the common structural motifs that enable heterologous nucleation.Target: DNAJB6 (DnaJ heat shock protein family member B6)
Supporting Evidence: DNAJB6 pote
🔍 Skeptic Identifies weaknesses, alternative explanations, and methodological concerns ▼
I'll critically evaluate each hypothesis, identifying weaknesses and providing counter-evidence where available.
Hypothesis 1: DNAJB6 Universal Cross-Seeding Inhibitor
Specific Weaknesses:
- The evidence primarily focuses on polyglutamine aggregation, not tau, α-synuclein, or TDP-43
- No direct evidence that DNAJB6 inhibits cross-seeding between different protein types
- The cited PMIDs don't actually support cross-seeding inhibition claims
- DNAJB6 overexpression can actually promote tau aggregation in some contexts by interfering with normal proteostasis (PMID
🎯 Domain Expert Assesses practical feasibility, druggability, and clinical translation ▼
PRACTICAL FEASIBILITY ASSESSMENT
Hypothesis 1: DNAJB6 Universal Cross-Seeding Inhibitor
Druggability: MODERATE-POOR
- Target Class: Heat shock protein co-chaperone (difficult to drug directly)
- Chemical Matter: Limited. No known direct DNAJB6 activators exist
- Existing Tools:
- HSP70 activators (YM-08, SW02) might indirectly enhance DNAJB6 function
- Gene therapy vectors for DNAJB6 overexpression (preclinical only)
- Direct competitors: None targeting DNAJB6 specifically
- Adjacent space: Multiple HSP70/HSP90 programs (Orphazy
⚖ Synthesizer Integrates perspectives and produces final ranked assessments ▼
Price History
7d Trend
↘
Falling
7d Momentum
▼ 19.9%
Volatility
Medium
0.0412
Events (7d)
4
⚡ Price Movement Log
Recent 15 events
| Event | Price | Change | Source | Time | |
|---|---|---|---|---|---|
| ⚖ | Recalibrated | $0.584 | ▲ 23.6% | calibrate_stale_price_his | 2026-04-26 13:47 |
| 📄 | New Evidence | $0.473 | ▲ 3.4% | evidence_batch_update | 2026-04-13 02:18 |
| 📄 | New Evidence | $0.457 | ▲ 6.2% | evidence_batch_update | 2026-04-13 02:18 |
| ⚖ | Recalibrated | $0.430 | ▼ 1.3% | 2026-04-10 15:58 | |
| ⚖ | Recalibrated | $0.436 | ▲ 1.5% | 2026-04-10 15:53 | |
| ⚖ | Recalibrated | $0.429 | ▲ 0.3% | 2026-04-08 18:39 | |
| ⚖ | Recalibrated | $0.428 | ▼ 0.8% | 2026-04-04 16:38 | |
| ⚖ | Recalibrated | $0.432 | ▼ 3.4% | 2026-04-04 16:02 | |
| 📄 | New Evidence | $0.447 | ▲ 4.0% | evidence_batch_update | 2026-04-04 09:08 |
| ⚖ | Recalibrated | $0.430 | ▼ 8.6% | 2026-04-03 23:46 | |
| 💬 | Debate Round | $0.470 | ▼ 21.1% | market_dynamics | 2026-04-03 08:23 |
| 💬 | Debate Round | $0.596 | ▲ 16.3% | market_dynamics | 2026-04-03 05:06 |
| 📊 | Score Update | $0.512 | ▼ 38.6% | market_dynamics | 2026-04-03 04:31 |
| 💬 | Debate Round | $0.835 | ▲ 67.6% | market_dynamics | 2026-04-03 03:06 |
| 📄 | New Evidence | $0.498 | ▼ 34.1% | market_dynamics | 2026-04-03 03:04 |
Clinical Trials (5) Relevance: 26%
0
Active
Active
0
Completed
Completed
1,820
Total Enrolled
Total Enrolled
NA
Highest Phase
Highest Phase
RECRUITING
·
NCT07402161 · IRCCS Policlinico S. Donato
250 enrolled · 2025-10-01 · → 2027-10-01
This study focuses on improving early detection of Alzheimer's disease (AD) in patients with subjective cognitive decline (SCD), a preclinical stage of cognitive impairment, in the context of emerging
Subjective Cognitive Decline (SCD) Subjective Cognitive Complaints (SCCs) Subjective Cognitive Impairment
COMPLETED
·
NCT06224920 · Ludwig-Maximilians - University of Munich
140 enrolled · 2017-01-01 · → 2024-01-01
The temporal sequence of microglial activation, changes in functional and structural connectivity and the progression of neurocognitive deficits has not been conclusively clarified. To date, there hav
Alzheimer Disease Corticobasal Syndrome
magnetic resonance imaging electroencephalography blood and CSF biomarker
RECRUITING
·
NCT06339190 · Monash University
1,000 enrolled · 2021-08-01 · → 2025-12
This cohort study aims to determine if a blood test can aid with diagnosing dementia in anyone presenting with cognitive complaints to a single healthcare network. The investigators will measure level
Neurodegenerative Diseases Dementia
Venepuncture
TERMINATED
·
NCT05815524 · Fondazione Policlinico Universitario Agostino Gemelli IRCCS
30 enrolled · 2022-05-02 · → 2024-12-31
Parkinson's disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigors, and tremor at rest. Distinctive neuropathological signs include progressive loss of dopaminergic neurons
Parkinson Disease
Physical activity training
UNKNOWN
·
NCT05807581 · Fondazione Policlinico Universitario Agostino Gemelli IRCCS
400 enrolled · 2023-06-09 · → 2025-05-30
In Parkinson's disease (PD), direct evidence linking inflammation to the harmful activities of alpha-synuclein (a-syn) aggregates, the disease onset, and its progression is still lacking. This transla
Parkinson Disease
physical activity iTBS
📚 Cited Papers (57)
TREM2-independent microgliosis promotes tau-mediated neurodegeneration in the presence of ApoE4.
Neuron (2023) · PMID:36368315
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
TREM2 interacts with TDP-43 and mediates microglial neuroprotection against TDP-43-related neurodegeneration.
Nature neuroscience (2022) · PMID:34916658
17 figures
Extended Data Fig. 1
Characterizations of GFP-hTDP-43 expression in a neonatal TDP-43 mouse model. GFP-hTDP-43 expression was induced via intracerebroventricular injection of AAV9.CAG.hTDP-43.GFP in C5...
pmc_api
Extended Data Fig. 2
Characterizations of motor deficits and neuronal loss in a neonatal TDP-43 mouse model. GFP-hTDP-43 expression was induced via intracerebroventricular injection of AAV9.CAG.hTDP-43...
pmc_api
Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy.
(1993) · PMID:20301376
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration.
Immunity (2023) · PMID:37442133
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease.
Cell (2017) · PMID:28602351
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
Increased plasma soluble TREM2 levels in non-Alzheimer's dementia.
Acta neurologica Belgica (2026) · PMID:41920402
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
AI-guided design of cyclic peptide binders targeting TREM2 using CycleRFdiffusion and experimental validation.
Bioorg Med Chem Lett (2026) · PMID:41435973
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
Loss of Triggering Receptor Expressed on Myeloid Cells 2 Impairs Microglial Function and Exacerbates Retinal Neurodegeneration in Glaucoma.
Am J Pathol (2026) · PMID:41643896
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
Microglial metabolic reprogramming in Alzheimer's disease: Pathways, mechanisms, and therapeutic implications.
Ageing Res Rev (2026) · PMID:41651180
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
Plant-derived bioactive compounds modulate the gut microbiota in Alzheimer's disease: Metabolite signaling, neuroimmune circuits, and systems-level regulation.
Phytomedicine (2026) · PMID:41678917
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
Triggering Receptor Expressed on Myeloid Cells-2 Regulates Innate Lymphoid Cell Levels in Bleomycin-Induced Pulmonary Fibrosis.
Kaohsiung J Med Sci (2026) · PMID:41928407
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
TREM2 deficiency delays postnatal microglial maturation and synaptic pruning, leading to anxiety-like behaviors.
J Alzheimers Dis (2026) · PMID:41930604
1 figure
Figures
Figures available at source paper (no open-access XML found).
deep_link
📅 Citation Freshness Audit
Freshness score = exp(-age×ln2/5): halves every 5 years. Green >0.6, Amber 0.3–0.6, Red <0.3.
No citation freshness data yet. Export bibliography — run scripts/audit_citation_freshness.py to populate.
📙 Related Wiki Pages (15)
Alzheimer's Drug Discovery Foundation (ADDF) institutionCorticobasal Syndrome (CBS) Treatment therapeuticsPSP Therapeutic Ideas treatmentPRX005 entityEED geneTREM2 Protein proteinTREM2 — Triggering Receptor Expressed on Myeloid C geneTREM2 Protein proteinTREM2 Mechanism Hub mechanismTREM2 — Triggering Receptor Expressed on Myeloid C geneNeurodegeneration diseasetrem2-alpha-synuclein-clearance-parkinsons generalAlibaba Tongyi Qianwen-Bio (Chinese Biomedical LLM ai_toolTREM2 Protein (Triggering Receptor Expressed on My entityTREM2 Modulator Therapy therapeutic
📓 Linked Notebooks (4)
📓 SciDEX Analysis: 2026 04 01 Gap 9137255B
Computational notebook for SDA-2026-04-01-gap-9137255b
📓 Protein aggregation cross-seeding across neurodegenerative diseases — Analysis Notebook
Jupyter notebook for analysis SDA-2026-04-01-gap-9137255b: What are the mechanisms underlying protein aggregation cross-seeding across neurodegenerative diseases?
📓 Protein aggregation cross-seeding across neurodegenerative diseases — Rich Analysis
Enhanced notebook with gene expression, pathway enrichment, score heatmaps, and statistical analysis. What are the mechanisms underlying protein aggregation cross-seeding across neurodegenerative dise …
📓 Protein aggregation cross-seeding across neurodegenerative diseases — Analysis Notebook
CI-generated notebook stub for analysis SDA-2026-04-01-gap-9137255b. What are the mechanisms underlying protein aggregation cross-seeding across neurodegenerative diseases?
📊 Resource Economics & ROI
High Efficiency
Resource Efficiency Score
0.85
61.0th percentile (776 hypotheses)
Tokens Used
5,377
KG Edges Generated
3,723
Citations Produced
25
Cost Ratios
Cost per KG Edge
122.20 tokens
Lower is better (baseline: 2000)
Cost per Citation
244.41 tokens
Lower is better (baseline: 1000)
Cost per Score Point
8961.67 tokens
Tokens / composite_score
Score Impact
Efficiency Boost to Composite
+0.085
10% weight of efficiency score
Adjusted Composite
0.669
How Economics Pricing Works
Hypotheses receive an efficiency score (0-1) based on how many knowledge graph edges and citations they produce per token of compute spent.
High-efficiency hypotheses (score >= 0.8) get a price premium in the market, pulling their price toward $0.580.
Low-efficiency hypotheses (score < 0.6) receive a discount, pulling their price toward $0.420.
Monthly batch adjustments update all composite scores with a 10% weight from efficiency, and price signals are logged to market history.
Efficiency Price Signals
| Date | Signal Price | Score |
|---|---|---|
| 2026-04-16T20:00 | $0.443 | 0.510 |
📋 Reviews View all →
Structured peer reviews assess evidence quality, novelty, feasibility, and impact. The Discussion thread below is separate: an open community conversation on this hypothesis.
💬 Discussion
No DepMap CRISPR Chronos data found for TREM2.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
Loading history…
⚖️ Governance History
No governance decisions recorded for this hypothesis.
Governance decisions are recorded when Senate quality gates, lifecycle transitions, Elo penalties, or pause grants affect this subject.
Wiki Pages
Alzheimer's Drug Discovery Foundation (ADDF)institutionCorticobasal Syndrome (CBS) TreatmenttherapeuticsPSP Therapeutic IdeastreatmentPRX005entityEEDgeneTREM2 ProteinproteinTREM2 — Triggering Receptor Expressed on Myeloid CgeneTREM2 ProteinproteinTREM2 Mechanism HubmechanismTREM2 — Triggering Receptor Expressed on Myeloid CgeneNeurodegenerationdiseasetrem2-alpha-synuclein-clearance-parkinsonsgeneralAlibaba Tongyi Qianwen-Bio (Chinese Biomedical LLMai_toolTREM2 Protein (Triggering Receptor Expressed on MyentityTREM2 Modulator Therapytherapeutic
KG Entities (39)
DNAJB6DNAJB6_proteinG3BP1HSPA8HSPG2PHB2RNA_bindingRNA_splicingTDP-43TGM2TREM2TREM2_proteinalpha-synucleinalzheimers_diseaseamyloid_formationamyloid_nucleationautophagybeta_sheet_structurecross_seedingfrontotemporal_dementia
Dependency Graph (3 upstream, 5 downstream)
Depends On
APOE-TREM2 Interaction Modulationrefines (0.5)TREM2-Dependent Microglial Senescence Transitionrefines (0.5)TREM2 Conformational Stabilizers for Synaptic Discriminationrefines (0.5)Depended On By
TREM2-P2RY12 Balance Restoration Therapyrefines (0.5)Oligodendrocyte Remyelination Enhancementrefines (0.5)TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegenerationrefines (0.5)TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegenerationrefines (0.5)TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegenerationrefines (0.5)Linked Experiments (6)
TREM2 KO amyloid pathology studyvalidation | tests | 0.80TREM2 KO amyloid pathology studyvalidation | tests | 0.80TREM2 KO amyloid pathology studyvalidation | tests | 0.80TREM2 KO amyloid pathology studyvalidation | tests | 0.80TREM2 KO amyloid pathology studyvalidation | tests | 0.80TREM2 KO amyloid pathology studyvalidation | tests | 0.20
Related Hypotheses
TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegeneration
Score: 0.892 | neurodegeneration
TREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau Clearance
Score: 0.861 | neuroscience
Microglial Senescence Prevention via TREM2/SASP Axis
Score: 0.837 | neurodegeneration
TREM2-Deficient Microglia as Drivers of Amyloid Plaque Toxicity in Alzheimer's Disease
Score: 0.827 | neurodegeneration
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Signaling
Score: 0.827 | neuroscience
Estimated Development
Estimated Cost
$0
Timeline
2.0 years
🧪 Falsifiable Predictions (4)
4 total
0 confirmed
0 falsified
If hypothesis is true, intervention require a systematic experimental approach combining protein engineering, cell biology, and in vivo testing
pending
conf: 0.50
Expected outcome: require a systematic experimental approach combining protein engineering, cell biology, and in vivo testing
Falsified by: Intervention fails to require a systematic experimental approach combining protein engineering, cell biology, and in vivo testing
If hypothesis is true, intervention focus on structural characterization of cross-seeded aggregates using cryo-electron microscopy and hydrogen-deuterium exchange mass spectrometry to identify unique conformational epitopes
pending
conf: 0.50
Expected outcome: focus on structural characterization of cross-seeded aggregates using cryo-electron microscopy and hydrogen-deuterium exchange mass spectrometry to identify unique conformational epitopes
Falsified by: Intervention fails to focus on structural characterization of cross-seeded aggregates using cryo-electron microscopy and hydrogen-deuterium exchange mass spectrometry to identify unique conformational epitopes
If hypothesis is true, intervention serve as specific molecular targets for engineered clearance systems
pending
conf: 0.50
Expected outcome: serve as specific molecular targets for engineered clearance systems
Falsified by: Intervention fails to serve as specific molecular targets for engineered clearance systems
If hypothesis is true, intervention revolutionize treatment approaches for neurodegenerative diseases
pending
conf: 0.50
Expected outcome: revolutionize treatment approaches for neurodegenerative diseases
Falsified by: Intervention fails to revolutionize treatment approaches for neurodegenerative diseases
Knowledge Subgraph (61 edges)
associated with (11)
cross-seeds (5)
encodes (5)
inhibits (5)
interacts with (1)
localizes to (5)
modulates (1)
promotes (8)
recruits (6)
▸ Show 1 more
regulates (2)
scaffolds (2)
Mechanism Pathway for TREM2
Molecular pathway showing key causal relationships underlying this hypothesis
graph TD
TREM2["TREM2"] -->|encodes| TREM2_protein["TREM2_protein"]
TREM2_1["TREM2"] -->|associated with| alzheimers_disease["alzheimers_disease"]
TREM2_protein_2["TREM2_protein"] -.->|inhibits| protein_aggregation["protein_aggregation"]
TREM2_protein_3["TREM2_protein"] -->|promotes| microglial_clearance["microglial_clearance"]
style TREM2 fill:#ce93d8,stroke:#333,color:#000
style TREM2_protein fill:#4fc3f7,stroke:#333,color:#000
style TREM2_1 fill:#ce93d8,stroke:#333,color:#000
style alzheimers_disease fill:#ef5350,stroke:#333,color:#000
style TREM2_protein_2 fill:#4fc3f7,stroke:#333,color:#000
style protein_aggregation fill:#4fc3f7,stroke:#333,color:#000
style TREM2_protein_3 fill:#4fc3f7,stroke:#333,color:#000
style microglial_clearance fill:#4fc3f7,stroke:#333,color:#000
3D Protein Structure
🧬 TREM2 — PDB 6YXY Click to expand 3D viewer
Source Analysis
Protein aggregation cross-seeding across neurodegenerative diseases
neurodegeneration | 2026-04-01 | completed
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Same Analysis (5)
Transglutaminase-2 Cross-Linking Inhibition Strategy
Score: 0.64 · TGM2
Glycosaminoglycan Template Disruption Approach
Score: 0.60 · HSPG2
Liquid-Liquid Phase Separation Modifier Therapy
Score: 0.55 · G3BP1
HSP70 Co-chaperone DNAJB6 Universal Cross-Seeding Inhibitor
Score: 0.54 · DNAJB6
Prohibitin-2 Mitochondrial Cross-Seeding Hub Disruption
→ View all analysis hypotheses
Score: 0.47 · PHB2