--- a/COBRAxy/docs/tools/marea.md	Mon Oct 27 12:33:08 2025 +0000
+++ b/COBRAxy/docs/tools/marea.md	Tue Oct 28 10:44:07 2025 +0000
@@ -1,279 +1,151 @@
 # MAREA
 
-Metabolic Reaction Enrichment Analysis for statistical comparison and map visualization.
+Metabolic Enrichment Analysis and Visualization.
 
 ## Overview
 
-MAREA performs statistical enrichment analysis on RAS/RPS data to identify significantly different metabolic reactions between sample groups. It generates enriched pathway maps with color-coded reactions showing statistical significance and fold changes.
+MAREA performs statistical comparison of metabolic scores (RAS/RPS) and visualizes results on pathway maps.
+
+## Galaxy Interface
+
+In Galaxy: **COBRAxy → Metabolic Reaction Enrichment Analysis**
 
-## Usage
+1. Upload RAS/RPS scores and sample class file
+2. Select map and configure statistical parameters
+3. Click **Run tool**
 
-### Command Line
+## Command-line console
 
 ```bash
-marea -td /path/to/COBRAxy \
-      -using_RAS true \
-      -input_data ras_data.tsv \
-      -input_class class_labels.tsv \
+marea -input_data scores.tsv \
+      -input_class classes.csv \
+      -choice_map ENGRO2 \
       -comparison manyvsmany \
-      -test ks \
-      -pv 0.05 \
-      -fc 1.5 \
-      -choice_map ENGRO2 \
-      -generate_svg true \
-      -idop results/
+      -pvalue 0.05 \
+      -idop output/
 ```
 
-### Galaxy Interface
-
-Select "MAREA" from the COBRAxy tool suite and configure analysis parameters through the web interface.
-
 ## Parameters
 
-### Required Parameters
-
-| Parameter | Flag | Description |
-|-----------|------|-------------|
-| Tool Directory | `-td, --tool_dir` | Path to COBRAxy installation directory |
-
-### Data Input Parameters
-
-| Parameter | Flag | Description | Default |
-|-----------|------|-------------|---------|
-| Use RAS | `-using_RAS, --using_RAS` | Include RAS analysis | true |
-| RAS Data | `-input_data, --input_data` | RAS scores TSV file | - |
-| RAS Classes | `-input_class, --input_class` | Sample group labels | - |
-| Multiple RAS | `-input_datas, --input_datas` | Multiple RAS files (space-separated) | - |
-| RAS Names | `-names, --names` | Names for multiple datasets | - |
-| Use RPS | `-using_RPS, --using_RPS` | Include RPS analysis | false |
-| RPS Data | `-input_data_rps, --input_data_rps` | RPS scores TSV file | - |
-| RPS Classes | `-input_class_rps, --input_class_rps` | RPS sample groups | - |
-
-### Statistical Parameters
-
 | Parameter | Flag | Description | Default |
 |-----------|------|-------------|---------|
-| Comparison Type | `-co, --comparison` | Statistical comparison mode | manyvsmany |
-| Statistical Test | `-te, --test` | Statistical test method | ks |
-| P-Value Threshold | `-pv, --pValue` | Significance threshold | 0.1 |
-| Adjusted P-values | `-adj, --adjusted` | Apply FDR correction | false |
-| Fold Change | `-fc, --fChange` | Minimum fold change | 1.5 |
-| Net Enrichment | `-ne, --net` | Use net enrichment for RPS | false |
-| Analysis Option | `-op, --option` | Analysis mode | datasets |
-
-### Visualization Parameters
-
-| Parameter | Flag | Description | Default |
-|-----------|------|-------------|---------|
-| Map Choice | `-choice_map, --choice_map` | Built-in metabolic map | - |
-| Custom Map | `-custom_map, --custom_map` | Path to custom SVG map | - |
-| Generate SVG | `-gs, --generate_svg` | Create SVG output | true |
-| Generate PDF | `-gp, --generate_pdf` | Create PDF output | false |
-| Generate PNG | `-gpng, --generate_png` | Create PNG output | false |
-| Color Map | `-colorm, --color_map` | Color scheme (jet/viridis) | jet |
-| Output Directory | `-idop, --output_path` | Results directory | result/ |
-
-### Advanced Parameters
-
-| Parameter | Flag | Description | Default |
-|-----------|------|-------------|---------|
-| Output Log | `-ol, --out_log` | Log file path | - |
-| Control Sample | `-on, --control` | Control group identifier | - |
+| Input Data | `-input_data` | RAS/RPS scores file | - |
+| Input Class | `-input_class` | Sample class definitions | - |
+| Map Choice | `-choice_map` | ENGRO2, Recon, or Custom | ENGRO2 |
+| Custom Map | `-custom_map` | Path to custom SVG map | - |
+| Comparison | `-comparison` | manyvsmany, onevsrest, onevsmany | manyvsmany |
+| P-value | `-pvalue` | Significance threshold | 0.05 |
+| FDR Correction | `-fdr` | Apply FDR correction | true |
+| Test Type | `-test_type` | t, wilcoxon, ks, DESeq | t |
+| Net RPS | `--net` | Use net contribution for reversible reactions (RPS only) | false |
+| Output Path | `-idop` | Output directory | marea/ |
 
 ## Input Formats
 
-### RAS/RPS Data File
-
-Tab-separated format with reactions as rows and samples as columns:
+### Metabolic Scores
 
 ```
-Reaction	Sample1	Sample2	Sample3	Sample4
-R00001	1.25	0.85	1.42	0.78
-R00002	0.65	1.35	0.72	1.28
-R00003	2.15	2.05	0.45	0.52
+Reaction	Sample1	Sample2	Sample3
+R00001	1.25	0.85	1.42
+R00002	0.65	1.35	0.72
 ```
 
-### Class Labels File
-
-Sample grouping information:
+### Sample Classes
 
 ```
-Sample	Class
+SampleID	Class
 Sample1	Control
 Sample2	Treatment
-Sample3	Control
-Sample4	Treatment
+Sample3	Treatment
 ```
 
-## Comparison Types
-
-### manyvsmany
-Compare all possible pairs of groups:
-- Group A vs Group B
-- Group A vs Group C  
-- Group B vs Group C
-
-### onevsrest
-Compare each group against all others combined:
-- Group A vs (Group B + Group C)
-- Group B vs (Group A + Group C)
-
-### onevsmany
-Compare one specific group against each other group separately:
-- Control vs Treatment1
-- Control vs Treatment2
+**File Format Notes:**
+- Use **tab-separated** values (TSV) or **comma-separated** (CSV)
+- First row must contain column headers
+- Sample names must match between scores and class file
+- Class names should not contain spaces
 
 ## Statistical Tests
 
-| Test | Description | Use Case |
-|------|-------------|----------|
-| `ks` | Kolmogorov-Smirnov | Non-parametric, distribution-free |
-| `ttest_p` | Paired t-test | Related samples |
-| `ttest_ind` | Independent t-test | Unrelated samples |
-| `wilcoxon` | Wilcoxon signed-rank | Non-parametric paired |
-| `mw` | Mann-Whitney U | Non-parametric independent |
-| `DESeq` | DESeq2-style analysis | Count-like data with dispersion |
+- **t**: Student's t-test (parametric, assumes normality)
+- **wilcoxon**: Wilcoxon/Mann-Whitney (non-parametric)
+- **ks**: Kolmogorov-Smirnov (distribution-free)
+- **DESeq**: DESeq2-like test (**RAS only**, requires ≥2 replicates per sample)
+
+## Comparison Types
 
-## Output Files
+- **manyvsmany**: All pairwise comparisons
+- **onevsrest**: Each class vs all others
+- **onevsmany**: One reference vs multiple classes
+
+## Advanced Options
+
+### Net RPS Values
 
-### Statistical Results
-- `comparison_stats.tsv`: P-values, fold changes, and test statistics
-- `enriched_reactions.tsv`: Significantly enriched reactions only
-- `comparison_summary.txt`: Analysis summary and parameters
+When analyzing RPS data with reversible reactions, the `--net` parameter controls arrow coloring:
+
+**When `--net false` (default):**
+- Each direction of a reversible reaction colored independently
+- Forward and backward contributions shown separately
 
-### Visualization
-- `pathway_map.svg`: Color-coded metabolic map
-- `pathway_map.pdf`: PDF version (if requested)
-- `pathway_map.png`: PNG version (if requested)
-- `legend.svg`: Color scale and significance indicators
+**When `--net true` (RPS only):**
+- Arrow tips colored with net contribution of both directions
+- Useful for visualizing overall metabolite flow direction
+
+**Note**: This option only applies to RPS analysis and affects visualization of reversible reactions on metabolic maps.
+
+## Output
+
+- `*_map.svg`: Annotated pathway maps
+- `comparison_results.tsv`: Statistical results
+- `*.log`: Processing log
 
 ## Examples
 
-### Basic RAS Analysis
+### Basic Analysis
 
 ```bash
-# Simple two-group comparison
-marea -td /opt/COBRAxy \
-      -using_RAS true \
-      -input_data ras_scores.tsv \
-      -input_class sample_groups.tsv \
+marea -input_data ras_scores.tsv \
+      -input_class classes.csv \
+      -choice_map ENGRO2 \
       -comparison manyvsmany \
-      -test ks \
-      -pv 0.05 \
-      -choice_map ENGRO2 \
+      -pvalue 0.05 \
       -idop results/
 ```
 
-### Combined RAS + RPS Analysis
+### Custom Map
 
 ```bash
-# Multi-modal analysis
-marea -td /opt/COBRAxy \
-      -using_RAS true \
-      -input_data ras_scores.tsv \
-      -input_class ras_groups.tsv \
-      -using_RPS true \
-      -input_data_rps rps_scores.tsv \
-      -input_class_rps rps_groups.tsv \
+marea -input_data rps_scores.tsv \
+      -input_class classes.csv \
+      -choice_map Custom \
+      -custom_map pathway.svg \
       -comparison onevsrest \
-      -test DESeq \
-      -adj true \
-      -fc 2.0 \
-      -choice_map HMRcore \
-      -generate_pdf true \
-      -idop multimodal_results/
-```
-
-### Multiple Dataset Analysis
-
-```bash
-# Compare multiple experiments
-marea -td /opt/COBRAxy \
-      -using_RAS true \
-      -input_datas exp1_ras.tsv exp2_ras.tsv exp3_ras.tsv \
-      -names "Experiment1" "Experiment2" "Experiment3" \
-      -comparison onevsmany \
-      -test wilcoxon \
-      -pv 0.01 \
-      -custom_map custom_pathway.svg \
-      -idop multi_experiment/
+      -idop results/
 ```
 
-## Map Visualization
-
-### Built-in Maps
-- **ENGRO2**: Human genome-scale reconstruction
-- **HMRcore**: Core human metabolic network  
-- **Recon**: Recon3D human model
-
-### Color Coding
-- **Red**: Significantly upregulated (high activity)
-- **Blue**: Significantly downregulated (low activity)
-- **Gray**: Not significant
-- **Line Width**: Proportional to fold change magnitude
-
-### Custom Maps
-SVG files with reaction elements having IDs matching your data:
-```xml
-<rect id="R00001" class="reaction" .../>
-<path id="R00002" class="reaction" .../>
-```
-
-## Quality Control
+### Non-parametric Test
 
-### Pre-analysis Checks
-- Verify sample names match between data and class files
-- Check for missing values and outliers
-- Ensure adequate sample sizes per group (n ≥ 3 recommended)
-
-### Post-analysis Validation
-- Review statistical distribution assumptions
-- Check multiple testing correction effects
-- Validate biological relevance of enriched pathways
-
-## Tips and Best Practices
-
-### Statistical Considerations
-- Use FDR correction (`-adj true`) for multiple comparisons
-- Choose appropriate tests based on data distribution
-- Consider effect size alongside significance
-
-### Visualization Optimization
-- Use high fold change thresholds (>2.0) for cleaner maps
-- Export both SVG (editable) and PDF (publication-ready) formats
-- Adjust color schemes for colorblind accessibility
+```bash
+marea -input_data scores.tsv \
+      -input_class classes.csv \
+      -choice_map ENGRO2 \
+      -test_type wilcoxon \
+      -pvalue 0.01 \
+      -fdr true \
+      -idop results/
+```
 
 ## Troubleshooting
 
-### Common Issues
-
-**No significant reactions found**
-- Lower p-value threshold (`-pv 0.1`)
-- Reduce fold change requirement (`-fc 1.2`)
-- Check sample group definitions
-
-**Map rendering errors**
-- Verify SVG map file integrity
-- Check reaction ID matching between data and map
-- Ensure sufficient system memory for large maps
-
-**Statistical test failures**
-- Verify data normality for parametric tests
-- Check for sufficient sample sizes
-- Consider alternative test methods
-
-## Integration
-
-### Upstream Tools
-- [RAS Generator](ras-generator.md) - Generate RAS scores
-- [RPS Generator](rps-generator.md) - Generate RPS scores
-
-### Downstream Analysis
-- [Flux to Map](flux-to-map.md) - Additional visualization options
-- [MAREA Cluster](marea-cluster.md) - Sample clustering analysis
+| Error | Solution |
+|-------|----------|
+| "No matching reactions" | Verify reaction IDs |
+| "Insufficient samples" | Increase sample sizes per group |
 
 ## See Also
 
-- [Statistical Tests Documentation](/tutorials/statistical-tests.md)
-- [Map Customization Guide](/tutorials/custom-maps.md)
-- [Multi-modal Analysis Tutorial](/tutorials/multimodal-analysis.md)
\ No newline at end of file
+- [RAS Generator](tools/ras-generator)
+- [RPS Generator](tools/rps-generator)
+- [Flux to Map](tools/flux-to-map)
+- [Built-in Models](reference/built-in-models)