@bgicli/bgicli 2.1.1 → 2.2.0

package/data/skills/hmdb-database/SKILL.md

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+---
+name: hmdb-database
+description: "Access Human Metabolome Database (220K+ metabolites). Search by name/ID/structure, retrieve chemical properties, biomarker data, NMR/MS spectra, pathways, for metabolomics and identification."
+---
+
+# HMDB Database
+
+## Overview
+
+The Human Metabolome Database (HMDB) is a comprehensive, freely available resource containing detailed information about small molecule metabolites found in the human body.
+
+## When to Use This Skill
+
+This skill should be used when performing metabolomics research, clinical chemistry, biomarker discovery, or metabolite identification tasks.
+
+## Database Contents
+
+HMDB version 5.0 (current as of 2025) contains:
+
+- **220,945 metabolite entries** covering both water-soluble and lipid-soluble compounds
+- **8,610 protein sequences** for enzymes and transporters involved in metabolism
+- **130+ data fields per metabolite** including:
+  - Chemical properties (structure, formula, molecular weight, InChI, SMILES)
+  - Clinical data (biomarker associations, diseases, normal/abnormal concentrations)
+  - Biological information (pathways, reactions, locations)
+  - Spectroscopic data (NMR, MS, MS-MS spectra)
+  - External database links (KEGG, PubChem, MetaCyc, ChEBI, PDB, UniProt, GenBank)
+
+## Core Capabilities
+
+### 1. Web-Based Metabolite Searches
+
+Access HMDB through the web interface at https://www.hmdb.ca/ for:
+
+**Text Searches:**
+- Search by metabolite name, synonym, or identifier (HMDB ID)
+- Example HMDB IDs: HMDB0000001, HMDB0001234
+- Search by disease associations or pathway involvement
+- Query by biological specimen type (urine, serum, CSF, saliva, feces, sweat)
+
+**Structure-Based Searches:**
+- Use ChemQuery for structure and substructure searches
+- Search by molecular weight or molecular weight range
+- Use SMILES or InChI strings to find compounds
+
+**Spectral Searches:**
+- LC-MS spectral matching
+- GC-MS spectral matching
+- NMR spectral searches for metabolite identification
+
+**Advanced Searches:**
+- Combine multiple criteria (name, properties, concentration ranges)
+- Filter by biological locations or specimen types
+- Search by protein/enzyme associations
+
+### 2. Accessing Metabolite Information
+
+When retrieving metabolite data, HMDB provides:
+
+**Chemical Information:**
+- Systematic name, traditional names, and synonyms
+- Chemical formula and molecular weight
+- Structure representations (2D/3D, SMILES, InChI, MOL file)
+- Chemical taxonomy and classification
+
+**Biological Context:**
+- Metabolic pathways and reactions
+- Associated enzymes and transporters
+- Subcellular locations
+- Biological roles and functions
+
+**Clinical Relevance:**
+- Normal concentration ranges in biological fluids
+- Biomarker associations with diseases
+- Clinical significance
+- Toxicity information when applicable
+
+**Analytical Data:**
+- Experimental and predicted NMR spectra
+- MS and MS-MS spectra
+- Retention times and chromatographic data
+- Reference peaks for identification
+
+### 3. Downloadable Datasets
+
+HMDB offers bulk data downloads at https://www.hmdb.ca/downloads in multiple formats:
+
+**Available Formats:**
+- **XML**: Complete metabolite, protein, and spectra data
+- **SDF**: Metabolite structure files for cheminformatics
+- **FASTA**: Protein and gene sequences
+- **TXT**: Raw spectra peak lists
+- **CSV/TSV**: Tabular data exports
+
+**Dataset Categories:**
+- All metabolites or filtered by specimen type
+- Protein/enzyme sequences
+- Experimental and predicted spectra (NMR, GC-MS, MS-MS)
+- Pathway information
+
+**Best Practices:**
+- Download XML format for comprehensive data including all fields
+- Use SDF format for structure-based analysis and cheminformatics workflows
+- Parse CSV/TSV formats for integration with data analysis pipelines
+- Check version dates to ensure up-to-date data (current: v5.0, 2023-07-01)
+
+**Usage Requirements:**
+- Free for academic and non-commercial research
+- Commercial use requires explicit permission (contact samackay@ualberta.ca)
+- Cite HMDB publication when using data
+
+### 4. Programmatic API Access
+
+**API Availability:**
+HMDB does not provide a public REST API. Programmatic access requires contacting the development team:
+
+- **Academic/Research groups:** Contact eponine@ualberta.ca (Eponine) or samackay@ualberta.ca (Scott)
+- **Commercial organizations:** Contact samackay@ualberta.ca (Scott) for customized API access
+
+**Alternative Programmatic Access:**
+- **R/Bioconductor**: Use the `hmdbQuery` package for R-based queries
+  - Install: `BiocManager::install("hmdbQuery")`
+  - Provides HTTP-based querying functions
+- **Downloaded datasets**: Parse XML or CSV files locally for programmatic analysis
+- **Web scraping**: Not recommended; contact team for proper API access instead
+
+### 5. Common Research Workflows
+
+**Metabolite Identification in Untargeted Metabolomics:**
+1. Obtain experimental MS or NMR spectra from samples
+2. Use HMDB spectral search tools to match against reference spectra
+3. Verify candidates by checking molecular weight, retention time, and MS-MS fragmentation
+4. Review biological plausibility (expected in specimen type, known pathways)
+
+**Biomarker Discovery:**
+1. Search HMDB for metabolites associated with disease of interest
+2. Review concentration ranges in normal vs. disease states
+3. Identify metabolites with strong differential abundance
+4. Examine pathway context and biological mechanisms
+5. Cross-reference with literature via PubMed links
+
+**Pathway Analysis:**
+1. Identify metabolites of interest from experimental data
+2. Look up HMDB entries for each metabolite
+3. Extract pathway associations and enzymatic reactions
+4. Use linked SMPDB (Small Molecule Pathway Database) for pathway diagrams
+5. Identify pathway enrichment for biological interpretation
+
+**Database Integration:**
+1. Download HMDB data in XML or CSV format
+2. Parse and extract relevant fields for local database
+3. Link with external IDs (KEGG, PubChem, ChEBI) for cross-database queries
+4. Build local tools or pipelines incorporating HMDB reference data
+
+## Related HMDB Resources
+
+The HMDB ecosystem includes related databases:
+
+- **DrugBank**: ~2,832 drug compounds with pharmaceutical information
+- **T3DB (Toxin and Toxin Target Database)**: ~3,670 toxic compounds
+- **SMPDB (Small Molecule Pathway Database)**: Pathway diagrams and maps
+- **FooDB**: ~70,000 food component compounds
+
+These databases share similar structure and identifiers, enabling integrated queries across human metabolome, drug, toxin, and food databases.
+
+## Best Practices
+
+**Data Quality:**
+- Verify metabolite identifications with multiple evidence types (spectra, structure, properties)
+- Check experimental vs. predicted data quality indicators
+- Review citations and evidence for biomarker associations
+
+**Version Tracking:**
+- Note HMDB version used in research (current: v5.0)
+- Databases are updated periodically with new entries and corrections
+- Re-query for updates when publishing to ensure current information
+
+**Citation:**
+- Always cite HMDB in publications using the database
+- Reference specific HMDB IDs when discussing metabolites
+- Acknowledge data sources for downloaded datasets
+
+**Performance:**
+- For large-scale analysis, download complete datasets rather than repeated web queries
+- Use appropriate file formats (XML for comprehensive data, CSV for tabular analysis)
+- Consider local caching of frequently accessed metabolite information
+
+## Reference Documentation
+
+See `references/hmdb_data_fields.md` for detailed information about available data fields and their meanings.

package/data/skills/hrd-analysis-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: 'hrd-analysis-agent'
+description: 'AI-powered homologous recombination deficiency (HRD) analysis for PARP inhibitor response prediction using genomic scarring signatures and BRCA pathway assessment.'
+measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes.
+allowed-tools:
+  - read_file
+  - run_shell_command
+---
+
+
+# HRD Analysis Agent
+
+The **HRD Analysis Agent** provides comprehensive analysis of homologous recombination deficiency for predicting response to PARP inhibitors and platinum chemotherapy. It integrates genomic scarring signatures (LOH, TAI, LST), BRCA1/2 status, and HRD gene pathway analysis.
+
+## When to Use This Skill
+
+* When determining HRD status for PARP inhibitor eligibility.
+* To calculate genomic instability scores (GIS) from tumor sequencing.
+* For analyzing BRCA1/2 and HRD gene mutations.
+* When predicting response to PARP inhibitors or platinum chemotherapy.
+* To identify "BRCAness" phenotype in BRCA wild-type tumors.
+
+## Core Capabilities
+
+1. **Genomic Scar Scoring**: Calculate LOH, TAI, and LST scores from copy number data.
+
+2. **BRCA Pathway Analysis**: Assess mutations in BRCA1, BRCA2, and 13 other HRD genes.
+
+3. **HRD Classification**: Determine HRD-positive vs. HRD-negative status.
+
+4. **PARP Inhibitor Prediction**: Predict response to olaparib, niraparib, rucaparib, talazoparib.
+
+5. **Platinum Sensitivity**: Predict platinum chemotherapy sensitivity.
+
+6. **Reversion Detection**: Identify BRCA reversion mutations restoring HR function.
+
+## HRD Scoring Components
+
+| Score | Definition | Biological Basis |
+|-------|------------|------------------|
+| LOH | Loss of heterozygosity regions >15 Mb | Genomic scarring |
+| TAI | Telomeric allelic imbalance | End-to-end fusions |
+| LST | Large-scale state transitions | Break-induced repair |
+| GIS | Combined LOH + TAI + LST | Overall HRD score |
+
+**HRD-Positive Threshold**: GIS ≥ 42 (Myriad myChoice) or equivalent
+
+## HRD Gene Panel
+
+| Gene | Function | HRD Contribution |
+|------|----------|------------------|
+| BRCA1 | HR core component | Major |
+| BRCA2 | RAD51 loading | Major |
+| PALB2 | BRCA2 partner | Moderate-Major |
+| RAD51C/D | HR mediators | Moderate |
+| ATM | DNA damage sensing | Moderate |
+| CHEK2 | Cell cycle checkpoint | Moderate |
+| BARD1 | BRCA1 partner | Moderate |
+| BRIP1 | Fanconi pathway | Moderate |
+| CDK12 | Transcription | Variable |
+| RAD51B | HR mediator | Low-Moderate |
+
+## Workflow
+
+1. **Input**: Copy number segments, somatic mutations, germline variants.
+
+2. **Scar Calculation**: Compute LOH, TAI, LST from segmented CNV data.
+
+3. **Gene Analysis**: Assess pathogenic variants in HRD genes.
+
+4. **Score Integration**: Calculate composite GIS score.
+
+5. **Classification**: Determine HRD status.
+
+6. **Reversion Check**: Screen for reversion mutations.
+
+7. **Output**: HRD score, classification, gene mutations, treatment recommendations.
+
+## Example Usage
+
+**User**: "Analyze HRD status for this ovarian cancer patient to guide PARP inhibitor selection."
+
+**Agent Action**:
+```bash
+python3 Skills/Oncology/HRD_Analysis_Agent/hrd_analyzer.py \
+    --cnv_segments tumor_segments.tsv \
+    --mutations somatic_variants.maf \
+    --germline germline_variants.vcf \
+    --tumor_type ovarian \
+    --purity 0.65 \
+    --ploidy 2.1 \
+    --output hrd_report.json
+```
+
+## Commercial HRD Tests
+
+| Test | Components | Threshold | FDA Status |
+|------|------------|-----------|------------|
+| myChoice CDx | GIS + BRCA | ≥42 or BRCA+ | FDA approved |
+| FoundationOne | LOH | ≥16% | FDA approved |
+| SOPHiA DDM HRD | GIS + BRCA | ≥42 or BRCA+ | CE-IVD |
+
+## Clinical Indications
+
+**FDA-Approved PARP Inhibitor Indications**:
+- **Ovarian**: HRD+ or BRCA+ (maintenance, later-line)
+- **Breast**: gBRCA+ (HER2-, metastatic)
+- **Pancreatic**: gBRCA+ (maintenance)
+- **Prostate**: HRR gene mutated (mCRPC)
+
+## Response Prediction
+
+| Status | PARP Response | Platinum Response |
+|--------|---------------|-------------------|
+| BRCA mutated | Very high | High |
+| HRD+ / BRCA WT | High | Moderate-High |
+| HRD- / BRCA WT | Limited | Standard |
+| Reversion+ | Poor | Poor |
+
+## AI/ML Components
+
+**GIS Calculation**:
+- ASCAT/FACETS for allele-specific CNV
+- HRDetect algorithm integration
+- ML refinement of thresholds
+
+**Reversion Detection**:
+- Frameshift restoration analysis
+- Splice site reversion
+- Secondary deletion removing stop
+
+**Response Prediction**:
+- Multi-feature model (GIS + genes + expression)
+- HRDetect signature scoring
+- Clinical outcome integration
+
+## Resistance Mechanisms
+
+| Mechanism | Detection | Implication |
+|-----------|-----------|-------------|
+| BRCA reversion | Sequencing | Acquired resistance |
+| 53BP1 loss | Expression/mutation | Rescued HR |
+| ABCB1 upregulation | Expression | Drug efflux |
+| PARP1 loss | Expression | Target loss |
+
+## Prerequisites
+
+* Python 3.10+
+* ASCAT/FACETS for CNV
+* HRDetect implementation
+* Germline/somatic variant callers
+
+## Related Skills
+
+* Variant_Interpretation - For BRCA classification
+* Liquid_Biopsy_Analytics_Agent - For ctDNA HRD monitoring
+* Pan_Cancer_MultiOmics_Agent - For multi-omic context
+
+## Special Considerations
+
+1. **Tumor Purity**: Low purity affects scar detection
+2. **Prior Therapy**: Platinum may select resistant clones
+3. **Germline Testing**: Important for family counseling
+4. **Reversion Monitoring**: Serial testing recommended
+
+## Author
+
+AI Group - Biomedical AI Platform
+
+
+<!-- AUTHOR_SIGNATURE: 9a7f3c2e-MD-BABU-MIA-2026-MSSM-SECURE -->

package/data/skills/hrv-alexithymia-expert/SKILL.md

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+---
+name: hrv-alexithymia-expert
+description: Heart rate variability biometrics and emotional awareness training. Expert in HRV analysis, interoception training, biofeedback, and emotional intelligence. Activate on 'HRV', 'heart rate variability',
+  'alexithymia', 'biofeedback', 'vagal tone', 'interoception', 'RMSSD', 'autonomic nervous system'. NOT for general fitness tracking without HRV focus, simple heart rate monitoring, or diagnosing medical
+  conditions (only licensed professionals diagnose).
+allowed-tools: Read,Write,Edit,Bash,mcp__firecrawl__firecrawl_search,WebFetch
+metadata:
+  category: Lifestyle & Personal
+  pairs-with:
+  - skill: jungian-psychologist
+    reason: Psychological context for HRV patterns
+  - skill: wisdom-accountability-coach
+    reason: Track emotional growth over time
+  tags:
+  - hrv
+  - biofeedback
+  - interoception
+  - emotional-awareness
+  - vagal
+---
+
+# HRV & Alexithymia Expert
+
+You are an expert in Heart Rate Variability (HRV) biometrics and Alexithymia (emotional awareness difficulties), specializing in the intersection of physiological signals and emotional intelligence.
+
+## Python Dependencies
+
+```bash
+pip install heartpy neurokit2 scipy numpy pandas matplotlib
+```
+
+## When to Use This Skill
+
+**Use for:**
+- HRV metric calculation and interpretation (SDNN, RMSSD, LF/HF)
+- Emotional awareness training with biofeedback
+- Interoception development exercises
+- Stress measurement and recovery tracking
+- Alexithymia assessment and intervention planning
+- Connecting body signals to emotional states
+
+**NOT for:**
+- General fitness tracking without HRV focus
+- Simple heart rate or pulse monitoring
+- Medical diagnosis (only licensed professionals diagnose)
+- Cardiac arrhythmia detection (requires medical devices)
+- Mental health crisis intervention (refer to professionals)
+
+## Core Competencies
+
+### Heart Rate Variability (HRV) Expertise
+- **HRV Metrics**: SDNN, RMSSD, pNN50, LF/HF ratio, and their meanings
+- **ANS Assessment**: Sympathetic vs. parasympathetic balance
+- **Stress Measurement**: Objective stress and recovery metrics
+- **Data Collection**: Wearables, chest straps, finger sensors, apps
+- **Interpretation**: Context-aware analysis of HRV patterns
+
+> For HRV metric calculations and code implementations, see `/references/hrv-metrics.md`
+
+### Alexithymia Understanding
+- **Definition**: Difficulty identifying and describing emotions
+- **Assessment**: TAS-20 (Toronto Alexithymia Scale) and other measures
+- **Subtypes**: Cognitive vs. affective alexithymia
+- **Neurobiological Basis**: Interoception, insular cortex function
+- **Co-occurring Conditions**: Autism, PTSD, anxiety, depression
+
+> For assessment details and vocabulary building, see `/references/alexithymia-assessment.md`
+
+### Integration: Body-Emotion Connection
+- **Interoception Training**: Learning to sense internal body signals
+- **Emotion Differentiation**: Using physical cues to identify emotions
+- **Biofeedback**: HRV training to improve emotional regulation
+- **Vagal Tone**: Strengthening parasympathetic response
+
+> For training protocols and exercises, see `/references/training-protocols.md`
+
+## HRV Interpretation Framework
+
+**High HRV** (RMSSD > 50ms, SDNN > 100ms):
+- ✅ Good stress resilience
+- ✅ Strong parasympathetic tone
+- ✅ Good recovery capacity
+- ✅ Cardiovascular health
+
+**Low HRV** (RMSSD < 20ms, SDNN < 50ms):
+- ⚠️ Chronic stress or overtraining
+- ⚠️ Poor recovery
+- ⚠️ Sympathetic dominance
+- ⚠️ Potential burnout
+
+**Context Matters:**
+- Time of day (lower in morning, higher at night)
+- Sleep quality (poor sleep = lower HRV)
+- Exercise (acute decrease, chronic increase)
+- Stress, hydration, alcohol, caffeine all affect HRV
+
+## Alexithymia Components
+
+**Three Core Components:**
+1. **Difficulty Identifying Feelings** (DIF) - Can't tell if anxious vs. angry vs. sad
+2. **Difficulty Describing Feelings** (DDF) - Limited emotional vocabulary
+3. **Externally-Oriented Thinking** (EOT) - Focus on external over internal
+
+**TAS-20 Scoring:**
+- Score < 51: Non-alexithymia
+- Score 52-60: Possible alexithymia
+- Score > 61: Alexithymia
+
+## Tools & Resources
+
+### HRV Measurement Devices
+**Consumer Grade**: Oura Ring, Apple Watch, WHOOP, Garmin, Polar H10
+**Clinical/Research**: Firstbeat Bodyguard, HeartMath Inner Balance, emWave Pro, Kubios HRV
+
+### HRV Apps
+Elite HRV, HRV4Training, Welltory, HeartMath
+
+## Anti-Patterns
+
+### Treating HRV as Absolute
+**What it looks like:** "Your RMSSD is 25, that's bad."
+**Why it's wrong:** HRV is individual. What matters is YOUR baseline and trends.
+**Instead:** Establish personal baseline over 2+ weeks, track relative changes.
+
+### Ignoring Context
+**What it looks like:** Interpreting morning HRV without considering last night's sleep, alcohol, or stress.
+**Why it's wrong:** HRV is affected by many factors; isolated readings are meaningless.
+**Instead:** Log context (sleep, stress, exercise, substances) alongside HRV.
+
+### Pathologizing Alexithymia
+**What it looks like:** Treating emotional unawareness as a defect to be "fixed."
+**Why it's wrong:** Alexithymia exists on a spectrum and has adaptive functions.
+**Instead:** Focus on expanding awareness gently, not "curing" a condition.
+
+### Replacing Professional Help
+**What it looks like:** Using HRV biofeedback as treatment for clinical conditions.
+**Why it's wrong:** HRV training is a tool, not therapy. Serious conditions need professionals.
+**Instead:** Use as complementary practice alongside professional treatment.
+
+## Key Principles
+
+1. **The Body Knows First**: HRV changes before conscious awareness
+2. **Measurement Enables Awareness**: Can't improve what you can't measure
+3. **Start With Physiology**: Easier to sense body than emotions
+4. **Build Bridges**: Connect HRV → Body sensations → Emotion labels
+5. **Practice = Progress**: Interoception is a trainable skill
+6. **Compassion Required**: Alexithymia isn't a choice or weakness
+
+---
+
+**Remember**: Emotional awareness isn't about having perfect words for feelings. It's about connecting with your internal experience, and HRV gives you a scientific window into that inner world. Start with the body, the emotions will follow.