@bgicli/bgicli 2.1.1 → 2.2.0

package/data/skills/aav-vector-design-agent/SKILL.md

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+<!--
+# COPYRIGHT NOTICE
+# This file is part of the "Universal Biomedical Skills" project.
+# Copyright (c) 2026 MD BABU MIA, PhD <md.babu.mia@mssm.edu>
+# All Rights Reserved.
+#
+# This code is proprietary and confidential.
+# Unauthorized copying of this file, via any medium is strictly prohibited.
+#
+# Provenance: Authenticated by MD BABU MIA
+
+-->
+
+---
+name: 'aav-vector-design-agent'
+description: 'AI-powered adeno-associated virus (AAV) vector design for gene therapy including capsid engineering, promoter selection, and tropism optimization.'
+measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes.
+allowed-tools:
+  - read_file
+  - run_shell_command
+---
+
+
+# AAV Vector Design Agent
+
+The **AAV Vector Design Agent** provides AI-driven design of adeno-associated virus vectors for gene therapy applications. It covers capsid selection and engineering, promoter/enhancer design, transgene optimization, and manufacturing considerations.
+
+## When to Use This Skill
+
+* When selecting optimal AAV serotype for tissue-specific targeting.
+* To design novel capsid variants with enhanced properties.
+* For optimizing transgene expression cassettes.
+* When predicting immunogenicity and neutralizing antibody escape.
+* To design liver-detargeted or CNS-tropic vectors.
+
+## Core Capabilities
+
+1. **Capsid Selection**: Match AAV serotype to target tissue based on tropism profiles.
+
+2. **Capsid Engineering**: Design modified capsids for enhanced transduction or immune evasion.
+
+3. **Promoter Design**: Select and optimize tissue-specific or ubiquitous promoters.
+
+4. **Transgene Optimization**: Codon optimization and regulatory element design.
+
+5. **Immunogenicity Prediction**: Predict NAb binding and T-cell epitopes.
+
+6. **Manufacturing Assessment**: Evaluate producibility and purification considerations.
+
+## AAV Serotype Tropism
+
+| Serotype | Primary Tropism | Clinical Use |
+|----------|-----------------|--------------|
+| AAV1 | Muscle, CNS | Glybera (muscle) |
+| AAV2 | Broad (liver, muscle) | Luxturna (retina) |
+| AAV5 | CNS, liver, retina | Hemgenix (liver) |
+| AAV8 | Liver, muscle | Multiple trials |
+| AAV9 | CNS, cardiac, liver | Zolgensma (CNS) |
+| AAVrh10 | CNS, liver | CNS trials |
+| AAVrh74 | Muscle | Elevidys (muscle) |
+| AAV-PHP.eB | CNS (mouse) | Research |
+
+## Workflow
+
+1. **Input**: Target tissue, therapeutic gene, patient population characteristics.
+
+2. **Capsid Selection**: Rank serotypes by tropism profile match.
+
+3. **Capsid Engineering**: Design modifications if needed (peptide insertion, point mutations).
+
+4. **Cassette Design**: Optimize ITR-to-ITR expression cassette.
+
+5. **Immunogenicity Analysis**: Predict NAb prevalence and T-cell epitopes.
+
+6. **Manufacturing Review**: Assess production feasibility.
+
+7. **Output**: Complete vector design with rationale.
+
+## Example Usage
+
+**User**: "Design an AAV vector for liver-directed gene therapy in hemophilia B with low immunogenicity."
+
+**Agent Action**:
+```bash
+python3 Skills/Gene_Therapy/AAV_Vector_Design_Agent/aav_designer.py \
+    --target_tissue liver \
+    --therapeutic_gene F9 \
+    --indication hemophilia_b \
+    --minimize_immunogenicity true \
+    --nab_escape true \
+    --promoter liver_specific \
+    --output aav_design/
+```
+
+## Expression Cassette Components
+
+```
+5' ITR - [Promoter] - [5' UTR] - [Transgene] - [WPRE] - [PolyA] - 3' ITR
+
+Packaging limit: ~4.7 kb between ITRs
+```
+
+**Promoter Options**:
+| Promoter | Type | Size | Application |
+|----------|------|------|-------------|
+| CAG | Ubiquitous | 1.7 kb | Strong expression |
+| EF1α | Ubiquitous | 1.2 kb | Constitutive |
+| LP1 | Liver-specific | 0.5 kb | Hepatocyte targeting |
+| hSyn | Neuron-specific | 0.5 kb | CNS applications |
+| MCK | Muscle-specific | 0.6 kb | Myopathies |
+| CMV | Ubiquitous | 0.6 kb | High initial (silenced) |
+
+## Capsid Engineering Strategies
+
+**Directed Evolution**:
+- Error-prone PCR libraries
+- DNA shuffling
+- Selection in target tissue
+
+**Rational Design**:
+- Peptide display (insertion in variable loops)
+- Point mutations for receptor targeting
+- Tyrosine-to-phenylalanine for stability
+
+**Machine Learning**:
+- Sequence-function models
+- Generative models for novel capsids
+- Tropism prediction
+
+## Immunogenicity Considerations
+
+**Pre-existing NAbs**:
+| Serotype | NAb Prevalence |
+|----------|----------------|
+| AAV2 | 30-60% |
+| AAV5 | 15-30% |
+| AAV8 | 15-25% |
+| AAV9 | 20-35% |
+
+**Mitigation Strategies**:
+- Serotype selection based on patient screening
+- Engineered NAb-evading capsids
+- Immunosuppression protocols
+- Plasmapheresis
+
+## AI/ML Components
+
+**Tropism Prediction**:
+- CNN on capsid sequence
+- Cell-type specific transduction
+- Cross-species translation
+
+**Immunogenicity Modeling**:
+- MHC binding prediction
+- T-cell epitope mapping
+- NAb epitope prediction
+
+**Expression Optimization**:
+- Codon optimization algorithms
+- RNA structure prediction
+- miRNA target site avoidance
+
+## Manufacturing Considerations
+
+| Factor | Impact | Optimization |
+|--------|--------|--------------|
+| Capsid yield | Production cost | Sequence modifications |
+| Empty/full ratio | Potency | Purification method |
+| Aggregation | Stability | Formulation |
+| DNA packaging | Transgene size | Cassette design |
+
+## Prerequisites
+
+* Python 3.10+
+* Sequence analysis tools
+* Immunoinformatics packages
+* Structural biology tools
+
+## Related Skills
+
+* CRISPR_Design_Agent - For gene editing payloads
+* Protein_Engineering - For capsid design
+* RNA_Therapeutics - For alternative modalities
+
+## Regulatory Considerations
+
+1. **Biodistribution**: Required for IND
+2. **Shedding**: Vector in bodily fluids
+3. **Germline transmission**: Gonadal presence
+4. **Integration risk**: Random vs site-specific
+5. **Immunogenicity**: Pre-existing and induced
+
+## Author
+
+AI Group - Biomedical AI Platform
+
+
+<!-- AUTHOR_SIGNATURE: 9a7f3c2e-MD-BABU-MIA-2026-MSSM-SECURE -->

package/data/skills/adaptyv/SKILL.md

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+---
+name: adaptyv
+description: Cloud laboratory platform for automated protein testing and validation. Use when designing proteins and needing experimental validation including binding assays, expression testing, thermostability measurements, enzyme activity assays, or protein sequence optimization. Also use for submitting experiments via API, tracking experiment status, downloading results, optimizing protein sequences for better expression using computational tools (NetSolP, SoluProt, SolubleMPNN, ESM), or managing protein design workflows with wet-lab validation.
+license: Unknown
+metadata:
+    skill-author: K-Dense Inc.
+---
+
+# Adaptyv
+
+Adaptyv is a cloud laboratory platform that provides automated protein testing and validation services. Submit protein sequences via API or web interface and receive experimental results in approximately 21 days.
+
+## Quick Start
+
+### Authentication Setup
+
+Adaptyv requires API authentication. Set up your credentials:
+
+1. Contact support@adaptyvbio.com to request API access (platform is in alpha/beta)
+2. Receive your API access token
+3. Set environment variable:
+
+```bash
+export ADAPTYV_API_KEY="your_api_key_here"
+```
+
+Or create a `.env` file:
+
+```
+ADAPTYV_API_KEY=your_api_key_here
+```
+
+### Installation
+
+Install the required package using uv:
+
+```bash
+uv pip install requests python-dotenv
+```
+
+### Basic Usage
+
+Submit protein sequences for testing:
+
+```python
+import os
+import requests
+from dotenv import load_dotenv
+
+load_dotenv()
+
+api_key = os.getenv("ADAPTYV_API_KEY")
+base_url = "https://kq5jp7qj7wdqklhsxmovkzn4l40obksv.lambda-url.eu-central-1.on.aws"
+
+headers = {
+    "Authorization": f"Bearer {api_key}",
+    "Content-Type": "application/json"
+}
+
+# Submit experiment
+response = requests.post(
+    f"{base_url}/experiments",
+    headers=headers,
+    json={
+        "sequences": ">protein1\nMKVLWALLGLLGAA...",
+        "experiment_type": "binding",
+        "webhook_url": "https://your-webhook.com/callback"
+    }
+)
+
+experiment_id = response.json()["experiment_id"]
+```
+
+## Available Experiment Types
+Adaptyv supports multiple assay types:
+- **Binding assays** - Test protein-target interactions using biolayer interferometry
+- **Expression testing** - Measure protein expression levels
+- **Thermostability** - Characterize protein thermal stability
+- **Enzyme activity** - Assess enzymatic function
+
+See `reference/experiments.md` for detailed information on each experiment type and workflows.
+
+## Protein Sequence Optimization
+Before submitting sequences, optimize them for better expression and stability:
+
+**Common issues to address:**
+- Unpaired cysteines that create unwanted disulfides
+- Excessive hydrophobic regions causing aggregation
+- Poor solubility predictions
+
+**Recommended tools:**
+- NetSolP / SoluProt - Initial solubility filtering
+- SolubleMPNN - Sequence redesign for improved solubility
+- ESM - Sequence likelihood scoring
+- ipTM - Interface stability assessment
+- pSAE - Hydrophobic exposure quantification
+
+See `reference/protein_optimization.md` for detailed optimization workflows and tool usage.
+
+## API Reference
+For complete API documentation including all endpoints, request/response formats, and authentication details, see `reference/api_reference.md`.
+
+## Examples
+For concrete code examples covering common use cases (experiment submission, status tracking, result retrieval, batch processing), see `reference/examples.md`.
+
+## Important Notes
+- Platform is currently in alpha/beta phase with features subject to change
+- Not all platform features are available via API yet
+- Results typically delivered in ~21 days
+- Contact support@adaptyvbio.com for access requests or questions
+- Suitable for high-throughput AI-driven protein design workflows
+

package/data/skills/adhd-daily-planner/SKILL.md

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+---
+name: adhd-daily-planner
+description: Time-blind friendly planning, executive function support, and daily structure for ADHD brains. Specializes in realistic time estimation, dopamine-aware task design, and building systems that
+  actually work for neurodivergent minds.
+allowed-tools: Read, Edit, Write, Bash, Glob, Grep, WebFetch, WebSearch, Task
+metadata:
+  category: Lifestyle & Personal
+  pairs-with:
+  - skill: project-management-guru-adhd
+    reason: Long-term project planning with ADHD context
+  - skill: wisdom-accountability-coach
+    reason: Accountability and habit tracking
+  tags:
+  - adhd
+  - productivity
+  - planning
+  - neurodivergent
+  - executive-function
+---
+
+# ADHD Daily Planner
+
+A planning system designed BY and FOR ADHD brains. This skill understands that traditional productivity advice fails for neurodivergent minds and provides strategies that work WITH your brain, not against it.
+
+## Core Philosophy
+
+ADHD is not a character flaw or lack of willpower. It's a difference in how the brain handles dopamine, time perception, and attention regulation. This skill:
+- Never uses shame or "just try harder" rhetoric
+- Builds systems around ADHD realities, not neurotypical ideals
+- Acknowledges that what works today might not work tomorrow
+- Celebrates done > perfect
+- Treats executive function as a battery that depletes
+
+## The ADHD Planning Paradox
+
+```
+Traditional Planning:
+1. Make detailed plan
+2. Follow plan
+3. Achieve goal
+
+ADHD Reality:
+1. Make detailed plan (hyperfocus, feels great)
+2. Plan feels constraining by day 2
+3. Rebel against own plan
+4. Feel guilty about abandoned plan
+5. Avoid thinking about goal entirely
+```
+
+This skill breaks the paradox by creating FLEXIBLE structures with BUILT-IN pivots.
+
+## Decision Tree
+
+```
+What time horizon are we planning?
+├── RIGHT NOW (next 2 hours) → Emergency brain dump + single next action
+├── TODAY → Time-blocked structure with transition buffers
+├── THIS WEEK → Theme days + priority winnowing
+├── THIS MONTH → Goal setting with anti-overwhelm safeguards
+└── LONGER → Break into month-sized chunks, don't over-plan
+
+Is the person in crisis mode?
+├── YES → Skip planning, identify ONE smallest possible action
+└── NO → Proceed with appropriate planning level
+
+Is the person hyperfocusing on planning itself?
+├── YES → Interrupt! Planning ≠ doing. Set timer, start ONE task.
+└── NO → Continue planning support
+```
+
+## Time Blindness Strategies
+
+### The ADHD Time Estimation Formula
+
+```
+Take your first estimate. Now:
+
+"5 minutes" → Actually 15-20 minutes
+"30 minutes" → Actually 1-1.5 hours
+"A couple hours" → Actually half a day
+"This weekend" → Actually won't happen without body doubling
+```
+
+**The 3x Rule**: Whatever you think it will take, multiply by 3. You're not bad at estimating—your brain processes time differently.
+
+### Making Time Visible
+
+- **Analog clocks** in every room (digital jumps; analog shows time PASSING)
+- **Time Timer** or similar visual countdown timers
+- **Calendar blocking** - if it's not on the calendar with a time, it doesn't exist
+- **"When, then" statements** - "When I finish my coffee, then I start the report"
+
+### Transition Time
+
+ADHD brains struggle with task transitions. BUILD IN BUFFERS:
+
+```
+Neurotypical Schedule:
+9:00 - Meeting
+10:00 - Deep work
+12:00 - Lunch
+
+ADHD-Friendly Schedule:
+9:00 - Meeting
+10:00 - [Transition buffer: bathroom, water, stare at wall]
+10:15 - Deep work
+11:45 - [Transition buffer: save work, prepare for context switch]
+12:00 - Lunch
+```
+
+## Daily Planning Template
+
+### Morning Brain Dump (5 min max - set timer!)
+
+```
+EVERYTHING IN MY HEAD RIGHT NOW:
+_________________________________
+_________________________________
+_________________________________
+_________________________________
+
+NOW CIRCLE ONLY 1-3 THINGS THAT ACTUALLY MATTER TODAY.
+```
+
+### The "3 Things" System
+
+Your daily plan is exactly 3 things:
+1. **THE Thing** - If you do nothing else, do this
+2. **Would Be Nice** - Important but not critical today
+3. **If I'm On Fire** - Only if crushing it
+
+That's it. Not 10 things. Not 5 things. THREE.
+
+### Time Blocking for ADHD
+
+```
+┌─────────────────────────────────────────────────────────────┐
+│ MORNING (Peak brain time for many - protect it!)           │
+├─────────────────────────────────────────────────────────────┤
+│ 9:00  - THE Thing (hardest/most important)                 │
+│         [Use body doubling, website blockers, timer]       │
+│ 10:30 - TRANSITION BUFFER (10-15 min)                      │
+│ 10:45 - Would Be Nice OR meetings                          │
+├─────────────────────────────────────────────────────────────┤
+│ MIDDAY (Energy dip - don't fight it)                       │
+├─────────────────────────────────────────────────────────────┤
+│ 12:00 - Lunch (actual break, not working lunch)            │
+│ 12:45 - Low-effort tasks: email, admin, organizing         │
+├─────────────────────────────────────────────────────────────┤
+│ AFTERNOON (Second wind for some)                           │
+├─────────────────────────────────────────────────────────────┤
+│ 2:00  - Collaborative work, meetings, variety tasks        │
+│ 4:00  - Wrap up, tomorrow prep (5 min), shutdown ritual    │
+└─────────────────────────────────────────────────────────────┘
+```
+
+## Executive Function Support
+
+### Task Initiation (The Hardest Part)
+
+**The 2-Minute Start**: Don't commit to finishing. Commit to 2 minutes.
+- "I'll just open the document"
+- "I'll just write the first sentence"
+- "I'll just look at the thing"
+
+**Body Doubling**: Work alongside someone (physically or virtually). The Focusmate app, Discord study groups, or just a friend on video call.
+
+**Temptation Bundling**: Pair unpleasant tasks with pleasant ones.
+- Boring data entry + favorite podcast
+- Exercise + audiobook
+- Cleaning + dance music
+
+### Working Memory Support
+
+ADHD working memory is limited. EXTERNALIZE EVERYTHING:
+
+- **Capture tools everywhere** - Notes app, physical notepad, voice memos
+- **Written instructions** even for simple things
+- **Checklists** for repeated tasks (even ones you've done 100 times)
+- **Visual reminders** in the physical space where you'll need them
+
+### Decision Fatigue
+
+ADHD brains make thousands of micro-decisions that drain the battery:
+
+**Pre-decide:**
+- Same breakfast every day (or rotate 2-3 options)
+- Outfit laid out night before
+- Default schedule for types of tasks
+- "If X, then Y" rules that don't require thinking
+
+## The Doom Box Strategy
+
+You have doom boxes. Admit it. Those piles of stuff you don't know what to do with.
+
+**Weekly Doom Box Protocol (15 min max):**
+1. Set timer for 15 minutes
+2. Pick up ONE item from the doom pile
+3. Decide: Trash / Donate / Home / Action needed
+4. If Action needed: write the action, put item in "action needed" zone
+5. Repeat until timer ends
+6. STOP. You did enough.
+
+## Anti-Patterns (Things That Don't Work)
+
+❌ **Detailed long-term planning** - You'll abandon it and feel bad
+❌ **Guilt-based motivation** - Creates avoidance, not action
+❌ **"I'll remember"** - You won't. Write it down.
+❌ **Willpower over systems** - Systems > willpower every time
+❌ **Comparing to neurotypical productivity** - Different brain, different metrics
+❌ **"Catching up" marathons** - You'll burn out. Slow and steady.
+❌ **Perfect planning before starting** - Planning paralysis. Start messy.
+
+## Good Days vs Bad Days
+
+ADHD has high variance. Plan for BOTH:
+
+**Good Days (Hyperfocus Available):**
+- Tackle THE Thing first while energy is there
+- Don't overcommit just because you're on fire
+- Bank some wins for bad days
+
+**Bad Days (Executive Function Depleted):**
+- Permission to do minimum viable
+- Focus on maintenance (eat, hygiene, rest)
+- Low-stakes tasks only
+- No major decisions
+
+**The key**: Don't judge bad days. They're part of the pattern.
+
+## Tools That Actually Help
+
+### Digital
+- **Focusmate** - Body doubling with strangers
+- **Forest** - Phone lockout with gamification
+- **Todoist/Things** - Simple task managers (NOT complex systems)
+- **Goblin Tools** - AI that breaks tasks into smaller steps
+
+### Physical
+- **Time Timer** - Visual countdown
+- **Whiteboard** - Daily view in prominent location
+- **Physical inbox tray** - One place for paper
+- **Fidget tools** - Support focus for many ADHD brains
+
+### Environmental
+- **Background noise** - Lo-fi beats, brown noise, coffee shop sounds
+- **Standing desk or movement option** - Bodies need to move
+- **Minimal visual clutter** - Less distraction
+- **Good lighting** - Affects focus more than you think
+
+## The Shutdown Ritual (5 min)
+
+End of workday ritual to actually STOP working:
+
+1. Write tomorrow's "THE Thing" (30 seconds)
+2. Check calendar for tomorrow surprises (30 seconds)
+3. Clear one small thing from inbox/desk (2 minutes)
+4. Say out loud: "Work is done for today." (Seriously. Say it.)
+5. Physical transition (close laptop, leave room, change clothes)
+
+## Integration with Other Skills
+
+- **adhd-design-expert**: For designing ADHD-friendly digital experiences
+- **diagramming-expert**: For visual task mapping
+- **jungian-psychologist**: For deeper patterns around productivity shame
+
+## Remember
+
+You are not broken. Your brain works differently. The goal isn't to become neurotypical—it's to build a life that works WITH your brain.
+
+Progress over perfection. Compassion over criticism. Systems over willpower.