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Skillstooluniverse-microbiome-research

tooluniverse-microbiome-research

Writing & research

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Updated 10-16 01:16

About this skill

Microbiome Research with ToolUniverse

Comprehensive microbiome analysis using MGnify (EBI metagenomics), GTDB (genome taxonomy), ENA (sequencing data), OLS (ontology lookup for ENVO biomes), and EuropePMC (literature).

Core Tools

Tool Purpose Auth
MGnify_search_studies Find metagenomics studies by biome/keyword None
MGnify_get_study_detail Study metadata, abstract, sample counts None
MGnify_list_analyses List taxonomic/functional analysis outputs for a study None
MGnify_get_taxonomy Taxonomic composition from an analysis None
MGnify_get_go_terms GO functional annotations from an analysis None
MGnify_get_interpro InterPro protein domain annotations None
MGnify_list_biomes Browse MGnify biome hierarchy None
MGnify_search_genomes Search metagenome-assembled genomes (MAGs) None
MGnify_get_genome Genome quality metrics (completeness, contamination) None
GTDB_search_genomes Search bacterial/archaeal genomes by taxonomy None
GTDB_get_species Species cluster details from GTDB None
GTDB_get_taxon_info Taxonomic rank info in GTDB hierarchy None
GTDB_search_taxon Search taxa by partial name across all ranks None
ENAPortal_search_studies Find sequencing studies in ENA. Query format: description="keyword" None
ENAPortal_search_samples Find samples with environmental metadata None
ols_search_terms Search ENVO ontology for biome/environment terms None
EuropePMC_search_articles Find microbiome publications None
PubMed_search_articles Literature search (different coverage than EuropePMC) None
BacDive_search_by_taxon List BacDive strain IDs for a genus (+ optional species) None
BacDive_get_strain Curated strain phenotype: morphology, Gram stain, culture temp/media, oxygen tolerance, isolation source None
MediaDive_search_media Find a cultivation medium by name substring None
MediaDive_get_medium Full recipe (ingredients + amounts + prep steps) for a medium None
MediaDive_search_ingredients / MediaDive_get_ingredient Look up a medium ingredient's chemical identifiers (CAS/ChEBI/PubChem) None
GMrepo_search_species Gut-microbiome sample counts and phenotype breadth for a species (96,000+ curated samples) None
GMrepo_get_phenotypes List/filter the 350+ health conditions GMrepo has gut-microbiome data for None

For drug-microbiome studies, also use:

  • PubChem_get_CID_by_compound_name / PubChem_get_compound_properties_by_CID — drug identity
  • CTD_get_chemical_gene_interactions — drug-gene interactions (e.g., metformin affects 1,175+ genes)
  • kegg_search_pathway / kegg_get_pathway_info — microbial metabolic pathways (butanoate, propanoate)
  • ReactomeAnalysis_pathway_enrichment — host pathway enrichment for drug-affected genes
  • drugbank_vocab_search — drug mechanism and targets

MGnify tip: Use concise single-keyword searches (e.g., "metformin") — multi-word queries may timeout. The MGnify API can be slow for broad searches.

Quick Start

from tooluniverse import ToolUniverse

tu = ToolUniverse()
tu.load_tools()

# 1. Search for gut microbiome studies
studies = tu.run_one_function({
    'name': 'MGnify_search_studies',
    'arguments': {'search': 'gut microbiome', 'size': 5}
})

# 2. Get study details
detail = tu.run_one_function({
    'name': 'MGnify_get_study_detail',
    'arguments': {'study_accession': 'MGYS00006860'}
})

# 3. List analyses for a study
analyses = tu.run_one_function({
    'name': 'MGnify_list_analyses',
    'arguments': {'study_accession': 'MGYS00006860', 'size': 5}
})

# 4. Get taxonomic profile from an analysis
taxonomy = tu.run_one_function({
    'name': 'MGnify_get_taxonomy',
    'arguments': {'analysis_id': 'MGYA00793746'}
})

# 5. Get functional annotations
go_terms = tu.run_one_function({
    'name': 'MGnify_get_go_terms',
    'arguments': {'analysis_id': 'MGYA00793746'}
})

Common Workflows

Workflow 1: Study Discovery by Environment

Find studies for a specific biome using MGnify's biome hierarchy:

# Browse biome hierarchy
biomes = tu.run_one_function({
    'name': 'MGnify_list_biomes',
    'arguments': {'lineage': 'root:Host-associated:Human', 'depth': 3}
})

# Search studies in a specific biome
studies = tu.run_one_function({
    'name': 'MGnify_search_studies',
    'arguments': {'biome': 'root:Host-associated:Human:Digestive system', 'size': 10}
})

# Look up ENVO ontology terms for environment metadata
envo = tu.run_one_function({
    'name': 'ols_search_terms',
    'arguments': {'query': 'human gut', 'ontology': 'envo', 'rows': 5}
})

Workflow 2: Taxonomic Profiling

Get the microbial composition of a metagenomics sample:

# Get analyses for a study
analyses = tu.run_one_function({
    'name': 'MGnify_list_analyses',
    'arguments': {'study_accession': 'MGYS00006860', 'size': 3}
})

# Get taxonomy for a specific analysis
taxonomy = tu.run_one_function({
    'name': 'MGnify_get_taxonomy',
    'arguments': {'analysis_id': 'MGYA00793746'}
})
# Returns organisms with lineage, abundance counts, and taxonomy rank

Workflow 3: Genome Quality Assessment

Evaluate metagenome-assembled genomes (MAGs):

# Search for genomes from a specific taxon
genomes = tu.run_one_function({
    'name': 'MGnify_search_genomes',
    'arguments': {'taxonomy': 'Faecalibacterium prausnitzii', 'page_size': 5}
})

# Get quality metrics for a genome
genome = tu.run_one_function({
    'name': 'MGnify_get_genome',
    'arguments': {'genome_id': 'MGYG000000001'}
})
# Returns completeness, contamination, N50, genome length, taxonomy

# Cross-reference with GTDB taxonomy
gtdb = tu.run_one_function({
    'name': 'GTDB_search_genomes',
    'arguments': {'operation': 'search_genomes', 'query': 'Faecalibacterium', 'items_per_page': 5}
})

Workflow 4: Functional Annotation

Discover functional potential of a metagenome:

# GO terms from an analysis
go_terms = tu.run_one_function({
    'name': 'MGnify_get_go_terms',
    'arguments': {'analysis_id': 'MGYA00793746'}
})

# InterPro domains
interpro = tu.run_one_function({
    'name': 'MGnify_get_interpro',
    'arguments': {'analysis_id': 'MGYA00793746'}
})

Workflow 5: Literature Integration

Combine metagenomics data with published research:

# Find relevant publications
papers = tu.run_one_function({
    'name': 'EuropePMC_search_articles',
    'arguments': {'query': 'gut microbiome AND Faecalibacterium AND (IBD OR "Crohn")', 'limit': 10}
})

# Find sequencing data in ENA
ena_studies = tu.run_one_function({
    'name': 'ENAPortal_search_studies',
    'arguments': {'query': 'description="gut microbiome 16S"', 'limit': 5}
})

Workflow 6: Strain Phenotype, Culturing Requirements, and Disease-Association Prevalence

Answer "what is this organism actually like and how prevalent is it in condition X" — a question MGnify/GTDB (composition and taxonomy only) can't answer:

# 1. Find BacDive strain IDs for a taxon (genus required, species optional)
strains = tu.run_one_function({
    'name': 'BacDive_search_by_taxon',
    'arguments': {'genus': 'Faecalibacterium', 'species': 'prausnitzii', 'limit': 3}
})
# -> [{'bacdive_id': 159475}, {'bacdive_id': 159476}, {'bacdive_id': 159477}]

# 2. Get the curated phenotype for one strain
strain = tu.run_one_function({
    'name': 'BacDive_get_strain',
    'arguments': {'bacdive_id': 159475}
})
# -> anaerobe, mesophilic (37C), isolated from human feces, grows on
#    "YCFA-MEDIUM (MODIFIED) (DSMZ Medium 1611)" and chopped-meat medium

# 3. Cross-reference the named medium in MediaDive for the actual recipe
medium = tu.run_one_function({
    'name': 'MediaDive_search_media',
    'arguments': {'query': 'YCFA'}
})
# -> medium_id 1611 matches the BacDive culture_media entry exactly
recipe = tu.run_one_function({
    'name': 'MediaDive_get_medium',
    'arguments': {'medium_id': 1611}
})
# -> full solution-by-solution ingredient list with amounts/units and prep steps

# 4. Check GMrepo for how prevalent/associated the species is in human gut studies
prevalence = tu.run_one_function({
    'name': 'GMrepo_search_species',
    'arguments': {'query': 'Faecalibacterium prausnitzii'}
})
# -> present in 21,286 of ~96,000 samples (22.0%), spanning 88 phenotypes

conditions = tu.run_one_function({
    'name': 'GMrepo_get_phenotypes',
    'arguments': {'query': 'Crohn'}
})
# -> Crohn Disease (MeSH D003424): 5,636 samples across 1,440 species, 602 genera

Reading BacDive's culture_media field: it names the medium (e.g. "YCFA-MEDIUM (MODIFIED) (DSMZ Medium 1611)") but gives no recipe — always follow up in MediaDive by searching the medium name to find its medium_id, then MediaDive_get_medium for the actual formulation. oxygen_tolerance can legitimately be an empty array (not curated for that strain) — don't infer aerobe/anaerobe status from an empty list.

GMrepo scope note: presented_samples/all_samples are curated sample COUNTS from public studies, not a claim about true population prevalence — a species absent from GMrepo's phenotype list for a condition may simply not have been studied there yet, not proven absent from that condition's gut microbiome.

MGnify Biome Hierarchy

Key biome lineages (use MGnify_list_biomes to discover others):

  • Human gut: root:Host-associated:Human:Digestive system
  • Human oral/skin: root:Host-associated:Human:Oral / root:Host-associated:Human:Skin
  • Soil: root:Environmental:Terrestrial:Soil
  • Ocean/Freshwater: root:Environmental:Aquatic:Marine / root:Environmental:Aquatic:Freshwater
  • Wastewater: root:Engineered:Wastewater

Key Identifiers

MGnify: studies=MGYS*, analyses=MGYA*, genomes=MGYG*. ENA studies=PRJEB*. GTDB genomes=GCA_*. ENVO terms=ENVO:* (e.g. ENVO:00002041). BacDive strain IDs and MediaDive medium/ingredient IDs are plain integers (occasionally suffixed, e.g. "1a") with no fixed prefix — always resolve via search first. GMrepo phenotypes use MeSH IDs (e.g. D003424 for Crohn Disease).

Reasoning Framework

Starting Point: Define the Question First

Microbiome analysis starts with: what is the question? LOOK UP DON'T GUESS — always check the study type and sequencing method before interpreting results.

Decision tree for data type:

  • Community composition (who is there?) → 16S/ITS amplicon → alpha/beta diversity, differential abundance
  • Functional potential (what can they do?) → Shotgun metagenomics → MGnify GO terms, InterPro, KEGG pathways
  • Active function (what are they doing now?) → Metatranscriptomics → specialized pipelines (not MGnify/GTDB alone)

Before calling any tool, determine which data type the user has via MGnify_get_study_detail — the pipeline type (amplicon vs shotgun) determines which analyses are valid. Do not apply 16S diversity metrics to metagenomic data or vice versa.

Dysbiosis Assessment Strategy

Dysbiosis (microbial imbalance) is context-dependent — there is no universal "healthy" microbiome. LOOK UP DON'T GUESS — compare to study-matched controls, not general population references.

  1. Check alpha diversity: Reduced Shannon index relative to controls suggests dysbiosis. Use MGnify_get_taxonomy to get community profiles, then assess richness and evenness.
  2. Identify keystone taxa shifts: Loss of known beneficial taxa (e.g., Faecalibacterium, Roseburia in gut) or bloom of pathobionts (e.g., Enterobacteriaceae). LOOK UP taxa roles with GTDB_get_species and literature via EuropePMC_search_articles.
  3. Functional consequences: Does taxonomic shift correlate with loss/gain of metabolic pathways? Check MGnify_get_go_terms and MGnify_get_interpro for the affected samples.
  4. Confounders: Antibiotics, diet, age, and geography all affect microbiome composition. A dysbiosis claim requires controlling for these factors or acknowledging them as limitations.

Taxonomic vs Functional Analysis: When to Use Each

  • Taxonomic analysis alone is sufficient when the question is "which organisms are present?" or "does community composition differ between groups?" Use MGnify_get_taxonomy + GTDB_search_genomes.
  • Functional analysis is needed when the question is "what metabolic capabilities differ?" or "why does a taxonomic shift matter?" Use MGnify_get_go_terms + MGnify_get_interpro + kegg_search_pathway.
  • Both together when linking organisms to functions (e.g., "which taxa drive butyrate production in healthy vs IBD gut?"). Cross-reference taxonomic profiles with functional annotations from the same MGnify analysis.

Evidence Grading

Tier Description Example
T1 Replicated finding across multiple cohorts with consistent effect Reduced Faecalibacterium in IBD (>10 independent studies)
T2 Single well-powered study (n > 100) with appropriate controls Metformin-associated Akkermansia enrichment in a controlled trial
T3 Pilot study or observational association, small sample size Taxonomic shift in n=15 case-control, no validation cohort
T4 Computational prediction or single-sample observation Novel MAG with predicted function, no culture confirmation

Interpretation Guidance

Alpha diversity (within-sample): Shannon index measures richness and evenness. Higher Shannon (>3.0 for gut) suggests a stable community. Reduced alpha diversity is associated with dysbiosis (IBD, antibiotics). Always compare to study-matched controls — diversity varies by body site, sequencing depth, and geography.

Beta diversity (between-sample): Bray-Curtis (abundance-based) or UniFrac (phylogenetic). PERMANOVA p < 0.05 with R-squared > 0.05 indicates condition-driven clustering. Low R-squared (<0.02) even with significant p suggests the effect is small relative to inter-individual variation. Choose weighted UniFrac when abundant taxa matter most; unweighted when rare taxa are important.

Taxonomic composition: Relative abundance at phylum level (Firmicutes/Bacteroidetes ratio) is a coarse indicator; genus- or species-level resolution is preferred. A taxon present at >1% relative abundance in multiple samples is reliably detected. Taxa at <0.1% may be noise or sequencing artifacts. GTDB taxonomy may reclassify NCBI names (e.g., Firmicutes split into multiple phyla).

Functional profiling: GO terms and InterPro domains from MGnify reflect the metabolic potential (not necessarily activity) of the community. Enrichment of specific pathways (e.g., butyrate production, LPS biosynthesis) should be interpreted alongside taxonomic data to identify which organisms contribute the functions.

Synthesis Questions

A complete microbiome report should answer:

  1. How does alpha diversity compare between conditions, and is the difference significant?
  2. Does beta diversity analysis show condition-driven clustering (PERMANOVA)?
  3. Which taxa are differentially abundant, and are they known commensals or pathobionts?
  4. What functional pathways are enriched, and which taxa likely drive them?
  5. How do findings compare to published studies for the same biome/condition (literature context)?

Tips

  • MGnify study accessions start with MGYS, analyses with MGYA, genomes with MGYG
  • Use MGnify_list_biomes first to find the correct biome lineage string
  • MGnify_get_taxonomy returns phylum-level to species-level composition
  • GTDB provides standardized bacterial/archaeal taxonomy (differs from NCBI in some lineages)
  • For 16S amplicon studies, taxonomy is the primary output; for shotgun metagenomics, both taxonomy and functional annotations are available
  • The size parameter in MGnify tools controls results per page (max 100)