@synsci/cli-darwin-x64-baseline 1.1.77 → 1.1.78

package/bin/skills/geo-database/references/geo_reference.md

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+# GEO Database Reference Documentation
+
+## Complete E-utilities API Specifications
+
+### Overview
+
+The NCBI Entrez Programming Utilities (E-utilities) provide programmatic access to GEO metadata through a set of nine server-side programs. All E-utilities return results in XML format by default.
+
+### Base URL
+
+```
+https://eutils.ncbi.nlm.nih.gov/entrez/eutils/
+```
+
+### Core E-utility Programs
+
+#### eSearch - Text Query to ID List
+
+**Purpose:** Search a database and return a list of UIDs matching the query.
+
+**URL Pattern:**
+```
+https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi
+```
+
+**Parameters:**
+- `db` (required): Database to search (e.g., "gds", "geoprofiles")
+- `term` (required): Search query string
+- `retmax`: Maximum number of UIDs to return (default: 20, max: 10000)
+- `retstart`: Starting position in result set (for pagination)
+- `usehistory`: Set to "y" to store results on history server
+- `sort`: Sort order (e.g., "relevance", "pub_date")
+- `field`: Limit search to specific field
+- `datetype`: Type of date to limit by
+- `reldate`: Limit to items within N days of today
+- `mindate`, `maxdate`: Date range limits (YYYY/MM/DD)
+
+**Example:**
+```python
+from Bio import Entrez
+Entrez.email = "your@email.com"
+
+# Basic search
+handle = Entrez.esearch(
+    db="gds",
+    term="breast cancer AND Homo sapiens",
+    retmax=100,
+    usehistory="y"
+)
+results = Entrez.read(handle)
+handle.close()
+
+# Results contain:
+# - Count: Total number of matches
+# - RetMax: Number of UIDs returned
+# - RetStart: Starting position
+# - IdList: List of UIDs
+# - QueryKey: Key for history server (if usehistory="y")
+# - WebEnv: Web environment string (if usehistory="y")
+```
+
+#### eSummary - Document Summaries
+
+**Purpose:** Retrieve document summaries for a list of UIDs.
+
+**URL Pattern:**
+```
+https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi
+```
+
+**Parameters:**
+- `db` (required): Database
+- `id` (required): Comma-separated list of UIDs or query_key+WebEnv
+- `retmode`: Return format ("xml" or "json")
+- `version`: Summary version ("2.0" recommended)
+
+**Example:**
+```python
+from Bio import Entrez
+Entrez.email = "your@email.com"
+
+# Get summaries for multiple IDs
+handle = Entrez.esummary(
+    db="gds",
+    id="200000001,200000002",
+    retmode="xml",
+    version="2.0"
+)
+summaries = Entrez.read(handle)
+handle.close()
+
+# Summary fields for GEO DataSets:
+# - Accession: GDS accession
+# - title: Dataset title
+# - summary: Dataset description
+# - PDAT: Publication date
+# - n_samples: Number of samples
+# - Organism: Source organism
+# - PubMedIds: Associated PubMed IDs
+```
+
+#### eFetch - Full Records
+
+**Purpose:** Retrieve full records for a list of UIDs.
+
+**URL Pattern:**
+```
+https://eutils.ncbi.nlm.nih.gov/entrez/eutils/efetch.fcgi
+```
+
+**Parameters:**
+- `db` (required): Database
+- `id` (required): Comma-separated list of UIDs
+- `retmode`: Return format ("xml", "text")
+- `rettype`: Record type (database-specific)
+
+**Example:**
+```python
+from Bio import Entrez
+Entrez.email = "your@email.com"
+
+# Fetch full records
+handle = Entrez.efetch(
+    db="gds",
+    id="200000001",
+    retmode="xml"
+)
+records = Entrez.read(handle)
+handle.close()
+```
+
+#### eLink - Cross-Database Linking
+
+**Purpose:** Find related records in same or different databases.
+
+**URL Pattern:**
+```
+https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi
+```
+
+**Parameters:**
+- `dbfrom` (required): Source database
+- `db` (required): Target database
+- `id` (required): UID from source database
+- `cmd`: Link command type
+  - "neighbor": Return linked UIDs (default)
+  - "neighbor_score": Return scored links
+  - "acheck": Check for links
+  - "ncheck": Count links
+  - "llinks": Return URLs to LinkOut resources
+
+**Example:**
+```python
+from Bio import Entrez
+Entrez.email = "your@email.com"
+
+# Find PubMed articles linked to a GEO dataset
+handle = Entrez.elink(
+    dbfrom="gds",
+    db="pubmed",
+    id="200000001"
+)
+links = Entrez.read(handle)
+handle.close()
+```
+
+#### ePost - Upload UID List
+
+**Purpose:** Upload a list of UIDs to the history server for use in subsequent requests.
+
+**URL Pattern:**
+```
+https://eutils.ncbi.nlm.nih.gov/entrez/eutils/epost.fcgi
+```
+
+**Parameters:**
+- `db` (required): Database
+- `id` (required): Comma-separated list of UIDs
+
+**Example:**
+```python
+from Bio import Entrez
+Entrez.email = "your@email.com"
+
+# Post large list of IDs
+large_id_list = [str(i) for i in range(200000001, 200000101)]
+handle = Entrez.epost(db="gds", id=",".join(large_id_list))
+result = Entrez.read(handle)
+handle.close()
+
+# Use returned QueryKey and WebEnv in subsequent calls
+query_key = result["QueryKey"]
+webenv = result["WebEnv"]
+```
+
+#### eInfo - Database Information
+
+**Purpose:** Get information about available databases and their fields.
+
+**URL Pattern:**
+```
+https://eutils.ncbi.nlm.nih.gov/entrez/eutils/einfo.fcgi
+```
+
+**Parameters:**
+- `db`: Database name (omit to get list of all databases)
+- `version`: Set to "2.0" for detailed field information
+
+**Example:**
+```python
+from Bio import Entrez
+Entrez.email = "your@email.com"
+
+# Get information about gds database
+handle = Entrez.einfo(db="gds", version="2.0")
+info = Entrez.read(handle)
+handle.close()
+
+# Returns:
+# - Database description
+# - Last update date
+# - Record count
+# - Available search fields
+# - Link information
+```
+
+### Search Field Qualifiers for GEO
+
+Common search fields for building targeted queries:
+
+**General Fields:**
+- `[Accession]`: GEO accession number
+- `[Title]`: Dataset title
+- `[Author]`: Author name
+- `[Organism]`: Source organism
+- `[Entry Type]`: Type of entry (e.g., "Expression profiling by array")
+- `[Platform]`: Platform accession or name
+- `[PubMed ID]`: Associated PubMed ID
+
+**Date Fields:**
+- `[Publication Date]`: Publication date (YYYY or YYYY/MM/DD)
+- `[Submission Date]`: Submission date
+- `[Modification Date]`: Last modification date
+
+**MeSH Terms:**
+- `[MeSH Terms]`: Medical Subject Headings
+- `[MeSH Major Topic]`: Major MeSH topics
+
+**Study Type Fields:**
+- `[DataSet Type]`: Type of study (e.g., "RNA-seq", "ChIP-seq")
+- `[Sample Type]`: Sample type
+
+**Example Complex Query:**
+```python
+query = """
+    (breast cancer[MeSH] OR breast neoplasms[Title]) AND
+    Homo sapiens[Organism] AND
+    expression profiling by array[Entry Type] AND
+    2020:2024[Publication Date] AND
+    GPL570[Platform]
+"""
+```
+
+## SOFT File Format Specification
+
+### Overview
+
+SOFT (Simple Omnibus Format in Text) is GEO's primary data exchange format. Files are structured as key-value pairs with data tables.
+
+### File Types
+
+**Family SOFT Files:**
+- Filename: `GSExxxxx_family.soft.gz`
+- Contains: Complete series with all samples and platforms
+- Size: Can be very large (100s of MB compressed)
+- Use: Complete data extraction
+
+**Series Matrix Files:**
+- Filename: `GSExxxxx_series_matrix.txt.gz`
+- Contains: Expression matrix with minimal metadata
+- Size: Smaller than family files
+- Use: Quick access to expression data
+
+**Platform SOFT Files:**
+- Filename: `GPLxxxxx.soft`
+- Contains: Platform annotation and probe information
+- Use: Mapping probes to genes
+
+### SOFT File Structure
+
+```
+^DATABASE = GeoMiame
+!Database_name = Gene Expression Omnibus (GEO)
+!Database_institute = NCBI NLM NIH
+!Database_web_link = http://www.ncbi.nlm.nih.gov/geo
+!Database_email = geo@ncbi.nlm.nih.gov
+
+^SERIES = GSExxxxx
+!Series_title = Study Title Here
+!Series_summary = Study description and background...
+!Series_overall_design = Experimental design...
+!Series_type = Expression profiling by array
+!Series_pubmed_id = 12345678
+!Series_submission_date = Jan 01 2024
+!Series_last_update_date = Jan 15 2024
+!Series_contributor = John,Doe
+!Series_contributor = Jane,Smith
+!Series_sample_id = GSMxxxxxx
+!Series_sample_id = GSMxxxxxx
+
+^PLATFORM = GPLxxxxx
+!Platform_title = Platform Name
+!Platform_distribution = commercial or custom
+!Platform_organism = Homo sapiens
+!Platform_manufacturer = Affymetrix
+!Platform_technology = in situ oligonucleotide
+!Platform_data_row_count = 54675
+#ID = Probe ID
+#GB_ACC = GenBank accession
+#SPOT_ID = Spot identifier
+#Gene Symbol = Gene symbol
+#Gene Title = Gene title
+!platform_table_begin
+ID    GB_ACC    SPOT_ID    Gene Symbol    Gene Title
+1007_s_at    U48705    -    DDR1    discoidin domain receptor...
+1053_at    M87338    -    RFC2    replication factor C...
+!platform_table_end
+
+^SAMPLE = GSMxxxxxx
+!Sample_title = Sample name
+!Sample_source_name_ch1 = cell line XYZ
+!Sample_organism_ch1 = Homo sapiens
+!Sample_characteristics_ch1 = cell type: epithelial
+!Sample_characteristics_ch1 = treatment: control
+!Sample_molecule_ch1 = total RNA
+!Sample_label_ch1 = biotin
+!Sample_platform_id = GPLxxxxx
+!Sample_data_processing = normalization method
+#ID_REF = Probe identifier
+#VALUE = Expression value
+!sample_table_begin
+ID_REF    VALUE
+1007_s_at    8.456
+1053_at    7.234
+!sample_table_end
+```
+
+### Parsing SOFT Files
+
+**With GEOparse:**
+```python
+import GEOparse
+
+# Parse series
+gse = GEOparse.get_GEO(filepath="GSE123456_family.soft.gz")
+
+# Access metadata
+metadata = gse.metadata
+phenotype_data = gse.phenotype_data
+
+# Access samples
+for gsm_name, gsm in gse.gsms.items():
+    sample_data = gsm.table
+    sample_metadata = gsm.metadata
+
+# Access platforms
+for gpl_name, gpl in gse.gpls.items():
+    platform_table = gpl.table
+    platform_metadata = gpl.metadata
+```
+
+**Manual Parsing:**
+```python
+import gzip
+
+def parse_soft_file(filename):
+    """Basic SOFT file parser"""
+    sections = {}
+    current_section = None
+    current_metadata = {}
+    current_table = []
+    in_table = False
+
+    with gzip.open(filename, 'rt') as f:
+        for line in f:
+            line = line.strip()
+
+            # New section
+            if line.startswith('^'):
+                if current_section:
+                    sections[current_section] = {
+                        'metadata': current_metadata,
+                        'table': current_table
+                    }
+                parts = line[1:].split(' = ')
+                current_section = parts[1] if len(parts) > 1 else parts[0]
+                current_metadata = {}
+                current_table = []
+                in_table = False
+
+            # Metadata
+            elif line.startswith('!'):
+                if in_table:
+                    in_table = False
+                key_value = line[1:].split(' = ', 1)
+                if len(key_value) == 2:
+                    key, value = key_value
+                    if key in current_metadata:
+                        if isinstance(current_metadata[key], list):
+                            current_metadata[key].append(value)
+                        else:
+                            current_metadata[key] = [current_metadata[key], value]
+                    else:
+                        current_metadata[key] = value
+
+            # Table data
+            elif line.startswith('#') or in_table:
+                in_table = True
+                current_table.append(line)
+
+    return sections
+```
+
+## MINiML File Format
+
+### Overview
+
+MINiML (MIAME Notation in Markup Language) is GEO's XML-based format for data exchange.
+
+### File Structure
+
+```xml
+<?xml version="1.0" encoding="UTF-8"?>
+<MINiML xmlns="http://www.ncbi.nlm.nih.gov/geo/info/MINiML"
+        xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
+  <Series iid="GDS123">
+    <Status>
+      <Submission-Date>2024-01-01</Submission-Date>
+      <Release-Date>2024-01-15</Release-Date>
+      <Last-Update-Date>2024-01-15</Last-Update-Date>
+    </Status>
+    <Title>Study Title</Title>
+    <Summary>Study description...</Summary>
+    <Overall-Design>Experimental design...</Overall-Design>
+    <Type>Expression profiling by array</Type>
+    <Contributor>
+      <Person>
+        <First>John</First>
+        <Last>Doe</Last>
+      </Person>
+    </Contributor>
+  </Series>
+
+  <Platform iid="GPL123">
+    <Title>Platform Name</Title>
+    <Distribution>commercial</Distribution>
+    <Technology>in situ oligonucleotide</Technology>
+    <Organism taxid="9606">Homo sapiens</Organism>
+    <Data-Table>
+      <Column position="1">
+        <Name>ID</Name>
+        <Description>Probe identifier</Description>
+      </Column>
+      <Data>
+        <Row>
+          <Cell column="1">1007_s_at</Cell>
+          <Cell column="2">U48705</Cell>
+        </Row>
+      </Data>
+    </Data-Table>
+  </Platform>
+
+  <Sample iid="GSM123">
+    <Title>Sample name</Title>
+    <Source>cell line XYZ</Source>
+    <Organism taxid="9606">Homo sapiens</Organism>
+    <Characteristics tag="cell type">epithelial</Characteristics>
+    <Characteristics tag="treatment">control</Characteristics>
+    <Platform-Ref ref="GPL123"/>
+    <Data-Table>
+      <Column position="1">
+        <Name>ID_REF</Name>
+      </Column>
+      <Column position="2">
+        <Name>VALUE</Name>
+      </Column>
+      <Data>
+        <Row>
+          <Cell column="1">1007_s_at</Cell>
+          <Cell column="2">8.456</Cell>
+        </Row>
+      </Data>
+    </Data-Table>
+  </Sample>
+</MINiML>
+```
+
+## FTP Directory Structure
+
+### Series Files
+
+**Pattern:**
+```
+ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE{nnn}nnn/GSE{xxxxx}/
+```
+
+Where `{nnn}` represents replacing last 3 digits with "nnn" and `{xxxxx}` is the full accession.
+
+**Example:**
+- GSE123456 → `/geo/series/GSE123nnn/GSE123456/`
+- GSE1234 → `/geo/series/GSE1nnn/GSE1234/`
+- GSE100001 → `/geo/series/GSE100nnn/GSE100001/`
+
+**Subdirectories:**
+- `/matrix/` - Series matrix files
+- `/soft/` - Family SOFT files
+- `/miniml/` - MINiML XML files
+- `/suppl/` - Supplementary files
+
+**File Types:**
+```
+matrix/
+  └── GSE123456_series_matrix.txt.gz
+
+soft/
+  └── GSE123456_family.soft.gz
+
+miniml/
+  └── GSE123456_family.xml.tgz
+
+suppl/
+  ├── GSE123456_RAW.tar
+  ├── filelist.txt
+  └── [various supplementary files]
+```
+
+### Sample Files
+
+**Pattern:**
+```
+ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM{nnn}nnn/GSM{xxxxx}/
+```
+
+**Subdirectories:**
+- `/suppl/` - Sample-specific supplementary files
+
+### Platform Files
+
+**Pattern:**
+```
+ftp://ftp.ncbi.nlm.nih.gov/geo/platforms/GPL{nnn}nnn/GPL{xxxxx}/
+```
+
+**File Types:**
+```
+soft/
+  └── GPL570.soft.gz
+
+miniml/
+  └── GPL570.xml
+
+annot/
+  └── GPL570.annot.gz  # Enhanced annotation (if available)
+```
+
+## Advanced GEOparse Usage
+
+### Custom Parsing Options
+
+```python
+import GEOparse
+
+# Parse with custom options
+gse = GEOparse.get_GEO(
+    geo="GSE123456",
+    destdir="./data",
+    silent=False,  # Show progress
+    how="full",  # Parse mode: "full", "quick", "brief"
+    annotate_gpl=True,  # Include platform annotation
+    geotype="GSE"  # Explicit type
+)
+
+# Access specific sample
+gsm = gse.gsms['GSM1234567']
+
+# Get expression values for specific probe
+probe_id = "1007_s_at"
+if hasattr(gsm, 'table'):
+    probe_data = gsm.table[gsm.table['ID_REF'] == probe_id]
+
+# Get all characteristics
+characteristics = {}
+for key, values in gsm.metadata.items():
+    if key.startswith('characteristics'):
+        for value in (values if isinstance(values, list) else [values]):
+            if ':' in value:
+                char_key, char_value = value.split(':', 1)
+                characteristics[char_key.strip()] = char_value.strip()
+```
+
+### Working with Platform Annotations
+
+```python
+import GEOparse
+import pandas as pd
+
+gse = GEOparse.get_GEO(geo="GSE123456", destdir="./data")
+
+# Get platform
+gpl = list(gse.gpls.values())[0]
+
+# Extract annotation table
+if hasattr(gpl, 'table'):
+    annotation = gpl.table
+
+    # Common annotation columns:
+    # - ID: Probe identifier
+    # - Gene Symbol: Gene symbol
+    # - Gene Title: Gene description
+    # - GB_ACC: GenBank accession
+    # - Gene ID: Entrez Gene ID
+    # - RefSeq: RefSeq accession
+    # - UniGene: UniGene cluster
+
+    # Map probes to genes
+    probe_to_gene = dict(zip(
+        annotation['ID'],
+        annotation['Gene Symbol']
+    ))
+
+    # Handle multiple probes per gene
+    gene_to_probes = {}
+    for probe, gene in probe_to_gene.items():
+        if gene and gene != '---':
+            if gene not in gene_to_probes:
+                gene_to_probes[gene] = []
+            gene_to_probes[gene].append(probe)
+```
+
+### Handling Large Datasets
+
+```python
+import GEOparse
+import pandas as pd
+import numpy as np
+
+def process_large_gse(gse_id, chunk_size=1000):
+    """Process large GEO series in chunks"""
+    gse = GEOparse.get_GEO(geo=gse_id, destdir="./data")
+
+    # Get sample list
+    sample_list = list(gse.gsms.keys())
+
+    # Process in chunks
+    for i in range(0, len(sample_list), chunk_size):
+        chunk_samples = sample_list[i:i+chunk_size]
+
+        # Extract data for chunk
+        chunk_data = {}
+        for gsm_id in chunk_samples:
+            gsm = gse.gsms[gsm_id]
+            if hasattr(gsm, 'table'):
+                chunk_data[gsm_id] = gsm.table['VALUE']
+
+        # Process chunk
+        chunk_df = pd.DataFrame(chunk_data)
+
+        # Save chunk results
+        chunk_df.to_csv(f"chunk_{i//chunk_size}.csv")
+
+        print(f"Processed {i+len(chunk_samples)}/{len(sample_list)} samples")
+```
+
+## Troubleshooting Common Issues
+
+### Issue: GEOparse Fails to Download
+
+**Symptoms:** Timeout errors, connection failures
+
+**Solutions:**
+1. Check internet connection
+2. Try downloading directly via FTP first
+3. Parse local files:
+```python
+gse = GEOparse.get_GEO(filepath="./local/GSE123456_family.soft.gz")
+```
+4. Increase timeout (modify GEOparse source if needed)
+
+### Issue: Missing Expression Data
+
+**Symptoms:** `pivot_samples()` fails or returns empty
+
+**Cause:** Not all series have series matrix files (older submissions)
+
+**Solution:** Parse individual sample tables:
+```python
+expression_data = {}
+for gsm_name, gsm in gse.gsms.items():
+    if hasattr(gsm, 'table') and 'VALUE' in gsm.table.columns:
+        expression_data[gsm_name] = gsm.table.set_index('ID_REF')['VALUE']
+
+expression_df = pd.DataFrame(expression_data)
+```
+
+### Issue: Inconsistent Probe IDs
+
+**Symptoms:** Probe IDs don't match between samples
+
+**Cause:** Different platform versions or sample processing
+
+**Solution:** Standardize using platform annotation:
+```python
+# Get common probe set
+all_probes = set()
+for gsm in gse.gsms.values():
+    if hasattr(gsm, 'table'):
+        all_probes.update(gsm.table['ID_REF'].values)
+
+# Create standardized matrix
+standardized_data = {}
+for gsm_name, gsm in gse.gsms.items():
+    if hasattr(gsm, 'table'):
+        sample_data = gsm.table.set_index('ID_REF')['VALUE']
+        standardized_data[gsm_name] = sample_data.reindex(all_probes)
+
+expression_df = pd.DataFrame(standardized_data)
+```
+
+### Issue: E-utilities Rate Limiting
+
+**Symptoms:** HTTP 429 errors, slow responses
+
+**Solution:**
+1. Get an API key from NCBI
+2. Implement rate limiting:
+```python
+import time
+from functools import wraps
+
+def rate_limit(calls_per_second=3):
+    min_interval = 1.0 / calls_per_second
+
+    def decorator(func):
+        last_called = [0.0]
+
+        @wraps(func)
+        def wrapper(*args, **kwargs):
+            elapsed = time.time() - last_called[0]
+            wait_time = min_interval - elapsed
+            if wait_time > 0:
+                time.sleep(wait_time)
+            result = func(*args, **kwargs)
+            last_called[0] = time.time()
+            return result
+        return wrapper
+    return decorator
+
+@rate_limit(calls_per_second=3)
+def safe_esearch(query):
+    handle = Entrez.esearch(db="gds", term=query)
+    results = Entrez.read(handle)
+    handle.close()
+    return results
+```
+
+### Issue: Memory Errors with Large Datasets
+
+**Symptoms:** MemoryError, system slowdown
+
+**Solution:**
+1. Process data in chunks
+2. Use sparse matrices for expression data
+3. Load only necessary columns
+4. Use memory-efficient data types:
+```python
+import pandas as pd
+
+# Read with specific dtypes
+expression_df = pd.read_csv(
+    "expression_matrix.csv",
+    dtype={'ID': str, 'GSM1': np.float32}  # Use float32 instead of float64
+)
+
+# Or use sparse format for mostly-zero data
+import scipy.sparse as sp
+sparse_matrix = sp.csr_matrix(expression_df.values)
+```
+
+## Platform-Specific Considerations
+
+### Affymetrix Arrays
+
+- Probe IDs format: `1007_s_at`, `1053_at`
+- Multiple probe sets per gene common
+- Check for `_at`, `_s_at`, `_x_at` suffixes
+- May need RMA or MAS5 normalization
+
+### Illumina Arrays
+
+- Probe IDs format: `ILMN_1234567`
+- Watch for duplicate probes
+- BeadChip-specific processing may be needed
+
+### RNA-seq
+
+- May not have traditional "probes"
+- Check for gene IDs (Ensembl, Entrez)
+- Counts vs. FPKM/TPM values
+- May need separate count files
+
+### Two-Channel Arrays
+
+- Look for `_ch1` and `_ch2` suffixes in metadata
+- VALUE_ch1, VALUE_ch2 columns
+- May need ratio or intensity values
+- Check dye-swap experiments
+
+## Best Practices Summary
+
+1. **Always set Entrez.email** before using E-utilities
+2. **Use API key** for better rate limits
+3. **Cache downloaded files** locally
+4. **Check data quality** before analysis
+5. **Verify platform annotations** are current
+6. **Document data processing** steps
+7. **Cite original studies** when using data
+8. **Check for batch effects** in meta-analyses
+9. **Validate results** with independent datasets
+10. **Follow NCBI usage guidelines**