Deep Full-Text Analysis of 16 HD Papers
Experiment #2 | March 30, 2026
Experiment Card
Experiment #1 read abstracts (200 words each). This experiment read entire papers end-to-end: Introduction, Methods, Results, Discussion, Conclusions. 1.9 million characters vs 4,400.
Top Findings
LIG1 K845N variant suppresses somatic CAG expansion
The K845N variant of DNA Ligase 1 confers enhanced substrate discrimination and increased repair fidelity, suppressing somatic CAG expansion in mouse models. This was only visible in the full Methods and Results sections.
CRISPR-Cas for precise HD genetic modification
Multiple papers confirm CRISPR technology can address the underlying genetic cause of HD, not just symptoms. Detailed protocols and in-vivo results were in the full text, absent from abstracts.
Mitochondrial dysfunction drives neuroinflammation across HD, AD, PD
Cross-disease pattern: mitochondrial DNA release triggers cGAS-STING pathway, causing neuroinflammation. This connection appeared in 3 papers and only became clear from reading the Discussion sections.
New Hypotheses (from full-text analysis)
cGAS-STING Pathway
cGAS mtDNA Inhibition
Inhibiting cGAS-mediated mitochondrial DNA release may reduce neuroinflammation across HD, AD, and PD. Found in 3 papers' Discussion sections.
DNA Repair
LIG1 K845N Target
The LIG1 K845N variant suppresses somatic CAG expansion and improves mitochondrial function. Potential therapeutic target for HD.
Gene Therapy
CRISPR Mito Delivery
CRISPR-Cas could deliver genes promoting mitochondrial biogenesis and function in neurodegenerative disease.
Promising Targets (from full text)
| Target | Papers | Why Promising |
|---|---|---|
| HTT CAG repeat | 4 | Root cause. Multiple therapeutic approaches targeting it directly. |
| cGAS | 3 | Mediates mtDNA-driven neuroinflammation. Cross-disease target (HD, AD, PD). |
| DNJC7 | 2 | Potent modifier of polyQ protein aggregation. |
| LIG1 | 1 | K845N variant suppresses somatic expansion. Novel finding from full text. |
Contradictions Found
No clear consensus on the role of copper homeostasis imbalance in neurodegenerative diseases. Some papers suggest it contributes to disease progression. Others don't mention it. This disagreement was only visible from reading full Discussion sections.
Gaps Identified
Gut microbiota dysbiosis in HD is poorly understood and barely studied.
Limited CRISPR-Cas research in human HD subjects. Most data is from animal models.
Limitations
- Only open-access papers (paywalled papers excluded)
- Single model (Llama 3.1 8B), single run
- Not reviewed by HD domain experts
- Context window limited very long papers
- AI-generated hypotheses are unvalidated starting points
Methodology
Data
Full text from PubMed Central (open access only)
Model
Llama 3.1 8B, 64K context, Ollama on Jetson AGX Orin
Analysis
Each full paper sent to LLM. Deep extraction + cross-paper synthesis.
Read Experiment #1 (abstracts) | Research Tracker | Dashboard