Cycle 1 Progress Report: Alzheimer’s Disease Target Prioritization — SEED SCORING Phase
Cycle 1 Progress Report: Alzheimer’s Disease Target Prioritization — SEED SCORING Phase
Executive Summary
No new data was added this cycle. This report reflects initial SEED SCORING efforts to rank Alzheimer’s disease candidate genes based on publication velocity as a fallback metric due to tool failures in retrieving genetic association, brain expression, and tractability scores from Open Targets. Rankings remain preliminary and are not biologically validated at this stage. The lack of progress in data retrieval is flagged as a critical blocker, requiring immediate strategic pivot to alternative data sources or manual curation.
Research Progress
- Loaded pre-defined seed gene pool (TREM2, PLCG2, PICALM, APP, APOE) for Alzheimer’s disease target prioritization.
- Attempted retrieval of genetic association, brain expression, and tractability scores from Open Targets; all requests failed, necessitating fallback to publication velocity as a proxy metric.
- Computed publication velocity for each gene using PubMed query results (2022–2025).
- Generated Cycle 1 Ranking artifact (
cycle_1_ranking.csv) based on fallback scoring.
Key Findings
[Output] Cycle 1 Ranking — Fallback (Tool Failures)
cycle_1_ranking.csv
| rank | symbol | publication_velocity | total_score |
|---|---|---|---|
| 1 | PICALM | 0.50 | 1 |
| 2 | TREM2 | 0.35 | 0.62 |
| 3 | APOE | 0.31 | 0.52 |
| 4 | APP | 0.10 | 0 |
PICALM ranked #1 in Cycle 1 with a publication velocity of 0.50, reflecting a 50% increase in Alzheimer’s-related publications from 2022–2023 to 2024–2025. TREM2 and APOE followed, scoring 0.35 and 0.31, respectively, while APP lagged significantly at 0.10. The stark contrast between APP’s low velocity and its historical saturation in Alzheimer’s research suggests publication fatigue for this target. Notably, PLCG2—hypothesized as a high-priority novel candidate—showed zero velocity change, indicating limited recent research activity despite its biological plausibility.
Quality Assessment
No formal quality assessment was conducted this cycle due to the absence of retrieved biological data. The reliance on publication velocity as a fallback metric introduces high risk of bias, as it does not account for genetic association strength, expression patterns, or tractability. The LEARNER agent reported no new sources or entities, triggering a YELLOW alert for data stagnation.
Budget Status
- Total Budget: $30.00
- Total Spent: $0.0048
- Budget Used: 0.02%
- Budget Remaining: $29.9952
Costs were negligible this cycle, primarily allocated to failed Open Targets queries and PubMed velocity calculations.
Issues & Risks
- Critical Blocker: Failure to retrieve genetic association, brain expression, and tractability scores from Open Targets, leaving the analysis incomplete and unvalidated.
- Data Stagnation: LEARNER agent identified no new sources or entities, risking project stall if unresolved.
- Fallback Metric Limitations: Publication velocity is a poor proxy for biological relevance, potentially skewing prioritization toward well-studied but therapeutically saturated targets.
- Tool Reliability: Over-reliance on automated tools (e.g., Open Targets API) without manual validation may perpetuate gaps.
Next Steps
Strategic Pivot Required:
- Manual Curation: Prioritize manual extraction of genetic association, brain expression, and tractability scores from alternative databases (e.g., GTEx, Allen Brain Atlas, UniProt) or published literature.
- Tool Diversification: Supplement Open Targets with direct queries to Ensembl, NCBI Gene, and Human Protein Atlas to cross-validate data.
- Expert Consultation: Engage domain experts to review seed gene pool and validate fallback metrics.
- Risk Mitigation: Develop contingency plans for tool failures, including pre-compiled datasets or partnerships with bioinformatics teams.
Do not proceed to Cycle 2 without resolving data retrieval failures.
Best Pick This Cycle
Name: PICALM Key Metrics:
- Publication Velocity: 0.50 (highest in cohort)
- Total Score: 1.0 (normalized)
- Recent Publications (2024–2025): 36
Confidence Level: Low
Rationale: PICALM ranked #1 based on publication velocity alone, but this metric does not reflect biological validity or tractability. The result is stale and unreliable without supporting genetic, expression, or tractability data. No definitive best pick can be endorsed at this stage.
Governance Status
-
Agent Alert Levels:
- PLANNER: GREEN (cost=$0.0006, time=877s)
- LEARNER: YELLOW (cost=$0.0000, time=472s)
- EXECUTOR: GREEN (cost=$0.0042, time=39s)
-
No MCDA governance data yet for this cycle.
Key Metrics
| Metric | Value |
|---|---|
| Sources Reviewed | 0 |
| Budget Used Pct | 0.02 |
| Budget Remaining Usd | 29.9952 |
| Tasks Completed | 1 |
| Risks Identified | 4 |
Agent Alert Levels
Agent Alert Levels (server-queried — not from compressed text):
PLANNER GREEN cost=$0.0006 time=877s
LEARNER YELLOW cost=$0.0000 time=472s
EXECUTOR GREEN cost=$0.0042 time=39s
A.G.E. Scores
(No AGE scores this cycle)
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