@bgicli/bgicli 2.1.1 → 2.2.0

package/data/skills/cobrapy/SKILL.md

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+---
+name: cobrapy
+description: "Constraint-based metabolic modeling (COBRA). FBA, FVA, gene knockouts, flux sampling, SBML models, for systems biology and metabolic engineering analysis."
+---
+
+# COBRApy - Constraint-Based Reconstruction and Analysis
+
+## Overview
+
+COBRApy is a Python library for constraint-based reconstruction and analysis (COBRA) of metabolic models, essential for systems biology research. Work with genome-scale metabolic models, perform computational simulations of cellular metabolism, conduct metabolic engineering analyses, and predict phenotypic behaviors.
+
+## Core Capabilities
+
+COBRApy provides comprehensive tools organized into several key areas:
+
+### 1. Model Management
+
+Load existing models from repositories or files:
+```python
+from cobra.io import load_model
+
+# Load bundled test models
+model = load_model("textbook")  # E. coli core model
+model = load_model("ecoli")     # Full E. coli model
+model = load_model("salmonella")
+
+# Load from files
+from cobra.io import read_sbml_model, load_json_model, load_yaml_model
+model = read_sbml_model("path/to/model.xml")
+model = load_json_model("path/to/model.json")
+model = load_yaml_model("path/to/model.yml")
+```
+
+Save models in various formats:
+```python
+from cobra.io import write_sbml_model, save_json_model, save_yaml_model
+write_sbml_model(model, "output.xml")  # Preferred format
+save_json_model(model, "output.json")  # For Escher compatibility
+save_yaml_model(model, "output.yml")   # Human-readable
+```
+
+### 2. Model Structure and Components
+
+Access and inspect model components:
+```python
+# Access components
+model.reactions      # DictList of all reactions
+model.metabolites    # DictList of all metabolites
+model.genes          # DictList of all genes
+
+# Get specific items by ID or index
+reaction = model.reactions.get_by_id("PFK")
+metabolite = model.metabolites[0]
+
+# Inspect properties
+print(reaction.reaction)        # Stoichiometric equation
+print(reaction.bounds)          # Flux constraints
+print(reaction.gene_reaction_rule)  # GPR logic
+print(metabolite.formula)       # Chemical formula
+print(metabolite.compartment)   # Cellular location
+```
+
+### 3. Flux Balance Analysis (FBA)
+
+Perform standard FBA simulation:
+```python
+# Basic optimization
+solution = model.optimize()
+print(f"Objective value: {solution.objective_value}")
+print(f"Status: {solution.status}")
+
+# Access fluxes
+print(solution.fluxes["PFK"])
+print(solution.fluxes.head())
+
+# Fast optimization (objective value only)
+objective_value = model.slim_optimize()
+
+# Change objective
+model.objective = "ATPM"
+solution = model.optimize()
+```
+
+Parsimonious FBA (minimize total flux):
+```python
+from cobra.flux_analysis import pfba
+solution = pfba(model)
+```
+
+Geometric FBA (find central solution):
+```python
+from cobra.flux_analysis import geometric_fba
+solution = geometric_fba(model)
+```
+
+### 4. Flux Variability Analysis (FVA)
+
+Determine flux ranges for all reactions:
+```python
+from cobra.flux_analysis import flux_variability_analysis
+
+# Standard FVA
+fva_result = flux_variability_analysis(model)
+
+# FVA at 90% optimality
+fva_result = flux_variability_analysis(model, fraction_of_optimum=0.9)
+
+# Loopless FVA (eliminates thermodynamically infeasible loops)
+fva_result = flux_variability_analysis(model, loopless=True)
+
+# FVA for specific reactions
+fva_result = flux_variability_analysis(
+    model,
+    reaction_list=["PFK", "FBA", "PGI"]
+)
+```
+
+### 5. Gene and Reaction Deletion Studies
+
+Perform knockout analyses:
+```python
+from cobra.flux_analysis import (
+    single_gene_deletion,
+    single_reaction_deletion,
+    double_gene_deletion,
+    double_reaction_deletion
+)
+
+# Single deletions
+gene_results = single_gene_deletion(model)
+reaction_results = single_reaction_deletion(model)
+
+# Double deletions (uses multiprocessing)
+double_gene_results = double_gene_deletion(
+    model,
+    processes=4  # Number of CPU cores
+)
+
+# Manual knockout using context manager
+with model:
+    model.genes.get_by_id("b0008").knock_out()
+    solution = model.optimize()
+    print(f"Growth after knockout: {solution.objective_value}")
+# Model automatically reverts after context exit
+```
+
+### 6. Growth Media and Minimal Media
+
+Manage growth medium:
+```python
+# View current medium
+print(model.medium)
+
+# Modify medium (must reassign entire dict)
+medium = model.medium
+medium["EX_glc__D_e"] = 10.0  # Set glucose uptake
+medium["EX_o2_e"] = 0.0       # Anaerobic conditions
+model.medium = medium
+
+# Calculate minimal media
+from cobra.medium import minimal_medium
+
+# Minimize total import flux
+min_medium = minimal_medium(model, minimize_components=False)
+
+# Minimize number of components (uses MILP, slower)
+min_medium = minimal_medium(
+    model,
+    minimize_components=True,
+    open_exchanges=True
+)
+```
+
+### 7. Flux Sampling
+
+Sample the feasible flux space:
+```python
+from cobra.sampling import sample
+
+# Sample using OptGP (default, supports parallel processing)
+samples = sample(model, n=1000, method="optgp", processes=4)
+
+# Sample using ACHR
+samples = sample(model, n=1000, method="achr")
+
+# Validate samples
+from cobra.sampling import OptGPSampler
+sampler = OptGPSampler(model, processes=4)
+sampler.sample(1000)
+validation = sampler.validate(sampler.samples)
+print(validation.value_counts())  # Should be all 'v' for valid
+```
+
+### 8. Production Envelopes
+
+Calculate phenotype phase planes:
+```python
+from cobra.flux_analysis import production_envelope
+
+# Standard production envelope
+envelope = production_envelope(
+    model,
+    reactions=["EX_glc__D_e", "EX_o2_e"],
+    objective="EX_ac_e"  # Acetate production
+)
+
+# With carbon yield
+envelope = production_envelope(
+    model,
+    reactions=["EX_glc__D_e", "EX_o2_e"],
+    carbon_sources="EX_glc__D_e"
+)
+
+# Visualize (use matplotlib or pandas plotting)
+import matplotlib.pyplot as plt
+envelope.plot(x="EX_glc__D_e", y="EX_o2_e", kind="scatter")
+plt.show()
+```
+
+### 9. Gapfilling
+
+Add reactions to make models feasible:
+```python
+from cobra.flux_analysis import gapfill
+
+# Prepare universal model with candidate reactions
+universal = load_model("universal")
+
+# Perform gapfilling
+with model:
+    # Remove reactions to create gaps for demonstration
+    model.remove_reactions([model.reactions.PGI])
+
+    # Find reactions needed
+    solution = gapfill(model, universal)
+    print(f"Reactions to add: {solution}")
+```
+
+### 10. Model Building
+
+Build models from scratch:
+```python
+from cobra import Model, Reaction, Metabolite
+
+# Create model
+model = Model("my_model")
+
+# Create metabolites
+atp_c = Metabolite("atp_c", formula="C10H12N5O13P3",
+                   name="ATP", compartment="c")
+adp_c = Metabolite("adp_c", formula="C10H12N5O10P2",
+                   name="ADP", compartment="c")
+pi_c = Metabolite("pi_c", formula="HO4P",
+                  name="Phosphate", compartment="c")
+
+# Create reaction
+reaction = Reaction("ATPASE")
+reaction.name = "ATP hydrolysis"
+reaction.subsystem = "Energy"
+reaction.lower_bound = 0.0
+reaction.upper_bound = 1000.0
+
+# Add metabolites with stoichiometry
+reaction.add_metabolites({
+    atp_c: -1.0,
+    adp_c: 1.0,
+    pi_c: 1.0
+})
+
+# Add gene-reaction rule
+reaction.gene_reaction_rule = "(gene1 and gene2) or gene3"
+
+# Add to model
+model.add_reactions([reaction])
+
+# Add boundary reactions
+model.add_boundary(atp_c, type="exchange")
+model.add_boundary(adp_c, type="demand")
+
+# Set objective
+model.objective = "ATPASE"
+```
+
+## Common Workflows
+
+### Workflow 1: Load Model and Predict Growth
+
+```python
+from cobra.io import load_model
+
+# Load model
+model = load_model("ecoli")
+
+# Run FBA
+solution = model.optimize()
+print(f"Growth rate: {solution.objective_value:.3f} /h")
+
+# Show active pathways
+print(solution.fluxes[solution.fluxes.abs() > 1e-6])
+```
+
+### Workflow 2: Gene Knockout Screen
+
+```python
+from cobra.io import load_model
+from cobra.flux_analysis import single_gene_deletion
+
+# Load model
+model = load_model("ecoli")
+
+# Perform single gene deletions
+results = single_gene_deletion(model)
+
+# Find essential genes (growth < threshold)
+essential_genes = results[results["growth"] < 0.01]
+print(f"Found {len(essential_genes)} essential genes")
+
+# Find genes with minimal impact
+neutral_genes = results[results["growth"] > 0.9 * solution.objective_value]
+```
+
+### Workflow 3: Media Optimization
+
+```python
+from cobra.io import load_model
+from cobra.medium import minimal_medium
+
+# Load model
+model = load_model("ecoli")
+
+# Calculate minimal medium for 50% of max growth
+target_growth = model.slim_optimize() * 0.5
+min_medium = minimal_medium(
+    model,
+    target_growth,
+    minimize_components=True
+)
+
+print(f"Minimal medium components: {len(min_medium)}")
+print(min_medium)
+```
+
+### Workflow 4: Flux Uncertainty Analysis
+
+```python
+from cobra.io import load_model
+from cobra.flux_analysis import flux_variability_analysis
+from cobra.sampling import sample
+
+# Load model
+model = load_model("ecoli")
+
+# First check flux ranges at optimality
+fva = flux_variability_analysis(model, fraction_of_optimum=1.0)
+
+# For reactions with large ranges, sample to understand distribution
+samples = sample(model, n=1000)
+
+# Analyze specific reaction
+reaction_id = "PFK"
+import matplotlib.pyplot as plt
+samples[reaction_id].hist(bins=50)
+plt.xlabel(f"Flux through {reaction_id}")
+plt.ylabel("Frequency")
+plt.show()
+```
+
+### Workflow 5: Context Manager for Temporary Changes
+
+Use context managers to make temporary modifications:
+```python
+# Model remains unchanged outside context
+with model:
+    # Temporarily change objective
+    model.objective = "ATPM"
+
+    # Temporarily modify bounds
+    model.reactions.EX_glc__D_e.lower_bound = -5.0
+
+    # Temporarily knock out genes
+    model.genes.b0008.knock_out()
+
+    # Optimize with changes
+    solution = model.optimize()
+    print(f"Modified growth: {solution.objective_value}")
+
+# All changes automatically reverted
+solution = model.optimize()
+print(f"Original growth: {solution.objective_value}")
+```
+
+## Key Concepts
+
+### DictList Objects
+Models use `DictList` objects for reactions, metabolites, and genes - behaving like both lists and dictionaries:
+```python
+# Access by index
+first_reaction = model.reactions[0]
+
+# Access by ID
+pfk = model.reactions.get_by_id("PFK")
+
+# Query methods
+atp_reactions = model.reactions.query("atp")
+```
+
+### Flux Constraints
+Reaction bounds define feasible flux ranges:
+- **Irreversible**: `lower_bound = 0, upper_bound > 0`
+- **Reversible**: `lower_bound < 0, upper_bound > 0`
+- Set both bounds simultaneously with `.bounds` to avoid inconsistencies
+
+### Gene-Reaction Rules (GPR)
+Boolean logic linking genes to reactions:
+```python
+# AND logic (both required)
+reaction.gene_reaction_rule = "gene1 and gene2"
+
+# OR logic (either sufficient)
+reaction.gene_reaction_rule = "gene1 or gene2"
+
+# Complex logic
+reaction.gene_reaction_rule = "(gene1 and gene2) or (gene3 and gene4)"
+```
+
+### Exchange Reactions
+Special reactions representing metabolite import/export:
+- Named with prefix `EX_` by convention
+- Positive flux = secretion, negative flux = uptake
+- Managed through `model.medium` dictionary
+
+## Best Practices
+
+1. **Use context managers** for temporary modifications to avoid state management issues
+2. **Validate models** before analysis using `model.slim_optimize()` to ensure feasibility
+3. **Check solution status** after optimization - `optimal` indicates successful solve
+4. **Use loopless FVA** when thermodynamic feasibility matters
+5. **Set fraction_of_optimum** appropriately in FVA to explore suboptimal space
+6. **Parallelize** computationally expensive operations (sampling, double deletions)
+7. **Prefer SBML format** for model exchange and long-term storage
+8. **Use slim_optimize()** when only objective value needed for performance
+9. **Validate flux samples** to ensure numerical stability
+
+## Troubleshooting
+
+**Infeasible solutions**: Check medium constraints, reaction bounds, and model consistency
+**Slow optimization**: Try different solvers (GLPK, CPLEX, Gurobi) via `model.solver`
+**Unbounded solutions**: Verify exchange reactions have appropriate upper bounds
+**Import errors**: Ensure correct file format and valid SBML identifiers
+
+## References
+
+For detailed workflows and API patterns, refer to:
+- `references/workflows.md` - Comprehensive step-by-step workflow examples
+- `references/api_quick_reference.md` - Common function signatures and patterns
+
+Official documentation: https://cobrapy.readthedocs.io/en/latest/

package/data/skills/compbioagent-explorer/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: compbioagent-explorer
+description: scRNA-seq Explorer
+keywords:
+  - single-cell
+  - visualization
+  - web-app
+  - cellxgene
+  - exploration
+measurable_outcome: Launch a local web instance for interactive scRNA-seq exploration and generate 3+ custom visualizations per session.
+license: MIT
+metadata:
+  author: CompBioAgent Team
+  version: "1.0.0"
+compatibility:
+  - system: Python 3.9+
+allowed-tools:
+  - run_shell_command
+  - web_fetch
+---
+
+# CompBioAgent (Single-Cell Explorer)
+
+An LLM-powered web application for single-cell RNA-seq data exploration, integrating with CellDepot and Cellxgene VIP.
+
+## When to Use
+
+*   **Interactive Exploration**: When you need to visually explore a dataset without writing code.
+*   **Hypothesis Generation**: Quickly checking expression of specific markers across clusters.
+*   **Sharing**: Presenting data to non-computational collaborators.
+
+## Core Capabilities
+
+1.  **Natural Language Querying**: "Show me the expression of TP53 in the B-cell cluster."
+2.  **Cellxgene Integration**: Leverages robust visualization tools.
+3.  **Data Integration**: Connects with CellDepot for dataset retrieval.
+
+## Workflow
+
+1.  **Setup**: `pip install compbioagent`.
+2.  **Launch**: `compbioagent start --data ./data.h5ad`.
+3.  **Interact**: Open the local URL (e.g., http://localhost:8050) and chat with the agent to generate plots.
+
+## Example Usage
+
+**User**: "Launch the explorer for my kidney dataset."
+
+**Agent Action**:
+```bash
+compbioagent launch --port 8080 --data ./kidney_atlas.h5ad
+```
+
+
+<!-- AUTHOR_SIGNATURE: 9a7f3c2e-MD-BABU-MIA-2026-MSSM-SECURE -->

package/data/skills/computational-pathology-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: computational-pathology-agent
+description: Analyze Whole Slide Images (WSI) for digital pathology, including tissue segmentation and feature extraction.
+keywords:
+  - wsi
+  - digital-pathology
+  - deep-learning
+  - resnet
+  - openslide
+measurable_outcome: Preprocess and extract tissue patches from a 1GB+ .svs slide within 15 minutes for downstream ML tasks.
+license: MIT
+metadata:
+  author: MD BABU MIA, PhD
+  version: "1.0.0"
+compatibility:
+  - system: python 3.9+
+allowed-tools:
+  - run_shell_command
+  - read_file
+  - write_file
+---
+
+# Computational Pathology Agent
+
+**Version:** 1.0.0
+**Author:** MD BABU MIA, PhD
+**Date:** February 2026
+
+## Overview
+This agent specializes in the analysis of Whole Slide Images (WSIs) for digital pathology. It leverages Deep Learning models (ResNet, ViT, HoverNet) to perform segmentation, classification, and feature extraction from gigapixel histology images.
+
+## Capabilities
+1.  **WSI Handling:** Efficient reading/tiling of .svs, .ndpi, .tiff files (using OpenSlide/TiffSlide).
+2.  **Tissue Segmentation:** Separation of tissue from background.
+3.  **Patch Extraction:** Automated generation of patches for ML training/inference.
+4.  **Nuclei Segmentation:** Integration with StarDist/HoverNet for cellular analysis.
+5.  **Feature Extraction:** Generating feature vectors for slide-level clustering.
+
+## Usage
+```python
+from Skills.Pathology_AI.Computational_Pathology_Agent.wsi_analyzer import WSIAnalyzer
+
+# Initialize
+path_agent = WSIAnalyzer(slide_path="./data/biopsy_001.svs")
+
+# Extract tissue patches
+path_agent.extract_patches(patch_size=256, level=1)
+
+# Analyze Nuclei (requires model weights)
+# path_agent.segment_nuclei()
+```
+
+## Requirements
+*   openslide-python
+*   opencv-python
+*   pytorch
+*   scikit-image
+
+<!-- AUTHOR_SIGNATURE: 9a7f3c2e-MD-BABU-MIA-2026-MSSM-SECURE -->

package/data/skills/convergence-study/SKILL.md

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+---
+name: convergence-study
+description: Spatial and temporal convergence analysis with Richardson extrapolation and Grid Convergence Index (GCI) for solution verification
+allowed-tools:
+  - Bash
+  - Read
+---
+
+# Convergence Study
+
+## Goal
+
+Provide script-driven convergence analysis for verifying that numerical solutions converge at the expected rate as the mesh or timestep is refined.
+
+## Requirements
+
+- Python 3.8+
+- NumPy (not required; scripts use only math stdlib)
+
+## Inputs to Gather
+
+| Input | Description | Example |
+|-------|-------------|---------|
+| Grid spacings | Sequence of mesh sizes (coarse to fine) | `0.4,0.2,0.1,0.05` |
+| Timestep sizes | Sequence of dt values | `0.04,0.02,0.01` |
+| Solution values | QoI at each refinement level | `1.16,1.04,1.01,1.0025` |
+| Expected order | Formal order of the numerical scheme | `2.0` |
+| Safety factor | GCI safety factor (1.25 default) | `1.25` |
+
+## Script Outputs (JSON Fields)
+
+| Script | Key Outputs |
+|--------|-------------|
+| `scripts/h_refinement.py` | `results.observed_orders`, `results.mean_order`, `results.richardson_extrapolated_value`, `results.convergence_assessment` |
+| `scripts/dt_refinement.py` | Same as h_refinement but for temporal convergence |
+| `scripts/richardson_extrapolation.py` | `results.extrapolated_value`, `results.error_estimate`, `results.observed_order` |
+| `scripts/gci_calculator.py` | `results.observed_order`, `results.gci_fine`, `results.gci_coarse`, `results.asymptotic_ratio`, `results.in_asymptotic_range` |
+
+## Workflow
+
+1. **Run grid/timestep refinement study** with at least 3 levels
+2. **Compute observed convergence order** with `h_refinement.py` or `dt_refinement.py`
+3. **Compare** observed order to expected order of the scheme
+4. **Estimate discretization error** via Richardson extrapolation
+5. **Report GCI** for formal solution verification using `gci_calculator.py`
+6. **Document** convergence results and any anomalies
+
+## Decision Guidance
+
+```
+Do you have 3+ refinement levels?
++-- YES --> Run h_refinement.py or dt_refinement.py
+|           +-- Observed order matches expected? --> Solution verified
+|           +-- Order too low? --> Check: pre-asymptotic, coding error, insufficient resolution
+|           +-- Order too high? --> Check: superconvergence or cancellation effects
++-- NO (only 2 levels) --> Use richardson_extrapolation.py with assumed order
+                           (less reliable without order verification)
+```
+
+## CLI Examples
+
+```bash
+# Spatial convergence with 4 grid levels
+python3 scripts/h_refinement.py --spacings 0.4,0.2,0.1,0.05 --values 1.16,1.04,1.01,1.0025 --expected-order 2.0 --json
+
+# Temporal convergence with 3 timestep levels
+python3 scripts/dt_refinement.py --timesteps 0.04,0.02,0.01 --values 2.12,2.03,2.0075 --expected-order 2.0 --json
+
+# Richardson extrapolation with assumed 2nd-order
+python3 scripts/richardson_extrapolation.py --spacings 0.02,0.01 --values 1.0032,1.0008 --order 2.0 --json
+
+# GCI for 3-mesh verification
+python3 scripts/gci_calculator.py --spacings 0.04,0.02,0.01 --values 1.0128,1.0032,1.0008 --json
+```
+
+## Error Handling
+
+| Error | Cause | Resolution |
+|-------|-------|------------|
+| `spacings and values must have the same length` | Mismatched input arrays | Provide equal-length lists |
+| `At least 2 refinement levels required` | Too few data points | Add more refinement levels |
+| `Exactly 3 refinement levels required` | GCI needs 3 levels | Provide fine/medium/coarse |
+| `Oscillatory convergence detected` | Non-monotone convergence | Check mesh quality or scheme |
+
+## Interpretation Guidance
+
+| Scenario | Meaning | Action |
+|----------|---------|--------|
+| Observed order matches expected | Solution in asymptotic range | Report GCI, extrapolate |
+| Observed order < expected | Pre-asymptotic or coding bug | Refine further or debug |
+| Negative observed order | Solution diverging | Check implementation |
+| GCI asymptotic ratio near 1.0 | Grids in asymptotic range | Results are reliable |
+| GCI asymptotic ratio far from 1.0 | Not in asymptotic range | Refine further |
+
+## References
+
+- `references/convergence_theory.md` - Formal convergence order, log-log analysis, asymptotic range
+- `references/gci_guidelines.md` - Roache's GCI method, ASME V&V 20, safety factors