napistu 0.1.0__py3-none-any.whl → 0.2.4.dev2__py3-none-any.whl

napistu/mechanism_matching.py

@@ -1,28 +1,117 @@
 from __future__ import annotations
 
 import logging
+from typing import Optional, Union, Set, Dict, List
 
 import igraph as ig
+import numpy as np
 import pandas as pd
+
+from napistu import identifiers
 from napistu import sbml_dfs_core
 from napistu import utils
 from napistu.constants import SBML_DFS
 from napistu.constants import CPR_EDGELIST
 from napistu.constants import CPR_EDGELIST_REQ_VARS
+from napistu.constants import FEATURE_ID_VAR_DEFAULT
+from napistu.constants import RESOLVE_MATCHES_AGGREGATORS
+from napistu.constants import RESOLVE_MATCHES_TMP_WEIGHT_COL
 from napistu.constants import IDENTIFIERS
 from napistu.constants import IDENTIFIER_EDGELIST_REQ_VARS
-from napistu.constants import SPECIES_IDENTIFIERS_REQUIRED_VARS
+from napistu.constants import ONTOLOGIES_LIST
 from napistu.network.constants import CPR_GRAPH_EDGES
 from napistu.network import paths
 
 logger = logging.getLogger(__name__)
 
 
+def bind_wide_results(
+    sbml_dfs: sbml_dfs_core.SBML_dfs,
+    results_df: pd.DataFrame,
+    results_name: str,
+    ontologies: Optional[Union[Set[str], Dict[str, str]]] = None,
+    dogmatic: bool = False,
+    species_identifiers: Optional[pd.DataFrame] = None,
+    feature_id_var: str = FEATURE_ID_VAR_DEFAULT,
+    numeric_agg: str = RESOLVE_MATCHES_AGGREGATORS.WEIGHTED_MEAN,
+    keep_id_col: bool = True,
+    verbose: bool = False,
+) -> sbml_dfs_core.SBML_dfs:
+    """
+    Binds wide results to a sbml_dfs object.
+
+    Take a table with molecular species-level attributes tied to systematic identifiers and match them to an sbml_dfs_model transferring these attributes to species_data
+
+    Parameters
+    ----------
+    sbml_dfs : sbml_dfs_core.SBML_dfs
+        The sbml_dfs object to bind the results to.
+    results_df : pd.DataFrame
+        The table containing the results to bind.
+    results_name : str
+        The name of the results to bind.
+    ontologies : Optional[Union[Set[str], Dict[str, str]]], default=None
+        Either:
+        - Set of columns to treat as ontologies (these should be entries in ONTOLOGIES_LIST )
+        - Dict mapping wide column names to ontology names in the ONTOLOGIES_LIST controlled vocabulary
+        - None to automatically detect valid ontology columns based on ONTOLOGIES_LIST
+    dogmatic : bool
+        Whether to respect differences between genes, transcripts, and proteins (True) or ignore them (False).
+    species_identifiers : Optional[pd.DataFrame]
+        Systematic identifiers for the molecular species "sbml_dfs". If None this will be generate on-the-fly.
+    feature_id_var : str
+        The name of the column in the results_df that contains the feature identifiers. If this does not exist it will be created.
+    numeric_agg : str
+        The aggregation method to use for resolving degeneracy.
+    keep_id_col : bool
+        Whether to keep the identifier column in the results_df.
+    verbose : bool
+        Whether to log cases of 1-to-many and many-to-one mapping and to indicate the behavior for resolving degeneracy
+
+    Returns
+    -------
+    sbml_dfs : sbml_dfs_core.SBML_dfs
+        The sbml_dfs object with the results bound.
+    """
+
+    species_identifiers = identifiers._prepare_species_identifiers(
+        sbml_dfs, dogmatic=dogmatic, species_identifiers=species_identifiers
+    )
+
+    # match
+    matched_s_ids_from_wide = match_features_to_wide_pathway_species(
+        results_df,
+        species_identifiers,
+        ontologies=ontologies,
+        feature_id_var=feature_id_var,
+        verbose=verbose,
+    )
+
+    disambiguated_matches = resolve_matches(
+        matched_data=matched_s_ids_from_wide,
+        feature_id_var=feature_id_var,
+        numeric_agg=numeric_agg,
+        keep_id_col=keep_id_col,
+    )
+
+    clean_species_data = utils.drop_extra_cols(
+        results_df, disambiguated_matches, always_include=[feature_id_var]
+    )
+
+    sbml_dfs.add_species_data(results_name, clean_species_data)
+
+    return sbml_dfs
+
+
 def features_to_pathway_species(
     feature_identifiers: pd.DataFrame,
     species_identifiers: pd.DataFrame,
     ontologies: set,
-    feature_id_var: str,
+    feature_identifiers_var: str = IDENTIFIERS.IDENTIFIER,
+    feature_id_var: str = FEATURE_ID_VAR_DEFAULT,
+    expand_identifiers: bool = False,
+    identifier_delimiter: str = "/",
+    verbose: bool = False,
 ) -> pd.DataFrame:
     """
     Features to Pathway Species
@@ -31,29 +120,64 @@ def features_to_pathway_species(
 
     Parameters:
     feature_identifiers: pd.DataFrame
-        pd.Dataframe containing a "feature_id_var" variable used to match entries
+        pd.Dataframe containing a "feature_identifiers_var" variable used to match entries
     species_identifiers: pd.DataFrame
         A table of molecular species identifiers produced from sbml_dfs.get_identifiers("species")
         generally using sbml_dfs_core.export_sbml_dfs()
     ontologies: set
         A set of ontologies used to match features to pathway species
-    feature_id_var: str
+    feature_identifiers_var: str
         Variable in "feature_identifiers" containing identifiers
+    expand_identifiers: bool, default=False
+        If True, split identifiers in feature_identifiers_var by identifier_delimiter and explode into multiple rows
+    identifier_delimiter: str, default="/"
+        Delimiter to use for splitting identifiers if expand_identifiers is True
+    verbose: bool, default=False
+        If True, log mapping statistics at the end of the function
 
     Returns:
     pathway_species: pd.DataFrame
         species_identifiers joined to feature_identifiers based on shared identifiers
     """
 
-    # map features to molecular features in the pathway
-    if feature_id_var not in feature_identifiers.columns.to_list():
+    # Check for identifier column
+    if feature_identifiers_var not in feature_identifiers.columns.to_list():
         raise ValueError(
-            f"{feature_id_var} must be a variable in 'feature_identifiers', "
+            f"{feature_identifiers_var} must be a variable in 'feature_identifiers', "
             f"possible variables are {', '.join(feature_identifiers.columns.tolist())}"
         )
 
+    # Respect or create feature_id column
+    feature_identifiers = _ensure_feature_id_var(feature_identifiers, feature_id_var)
+
+    # Optionally expand identifiers into multiple rows
+    if expand_identifiers:
+        # Count the number of expansions by counting delimiters
+        n_expansions = (
+            feature_identifiers[feature_identifiers_var]
+            .astype(str)
+            .str.count(identifier_delimiter)
+            .sum()
+        )
+        if n_expansions > 0:
+            logger.info(
+                f"Expanding identifiers: {n_expansions} delimiters found in '{feature_identifiers_var}', will expand to more rows."
+            )
+
+        # Split, strip whitespace, and explode
+        feature_identifiers = feature_identifiers.copy()
+        feature_identifiers[feature_identifiers_var] = (
+            feature_identifiers[feature_identifiers_var]
+            .astype(str)
+            .str.split(identifier_delimiter)
+            .apply(lambda lst: [x.strip() for x in lst])
+        )
+        feature_identifiers = feature_identifiers.explode(
+            feature_identifiers_var, ignore_index=True
+        )
+
     # check identifiers table
-    _check_species_identifiers_table(species_identifiers)
+    identifiers._check_species_identifiers_table(species_identifiers)
 
     available_ontologies = set(species_identifiers[IDENTIFIERS.ONTOLOGY].tolist())
     unavailable_ontologies = ontologies.difference(available_ontologies)
@@ -80,7 +204,9 @@ def features_to_pathway_species(
 
     # map features to pathway species
     pathway_species = feature_identifiers.merge(
-        relevant_identifiers, left_on=feature_id_var, right_on=IDENTIFIERS.IDENTIFIER
+        relevant_identifiers,
+        left_on=feature_identifiers_var,
+        right_on=IDENTIFIERS.IDENTIFIER,
     )
 
     if pathway_species.shape[0] == 0:
@@ -90,12 +216,18 @@ def features_to_pathway_species(
         None
 
     # report the fraction of unmapped species
+    if verbose:
+        _log_feature_species_mapping_stats(pathway_species, feature_id_var)
 
     return pathway_species
 
 
 def edgelist_to_pathway_species(
-    formatted_edgelist: pd.DataFrame, species_identifiers: pd.DataFrame, ontologies: set
+    formatted_edgelist: pd.DataFrame,
+    species_identifiers: pd.DataFrame,
+    ontologies: set,
+    feature_id_var: str = FEATURE_ID_VAR_DEFAULT,
+    verbose: bool = False,
 ) -> pd.DataFrame:
     """
     Edgelist to Pathway Species
@@ -110,6 +242,10 @@ def edgelist_to_pathway_species(
         sbml_dfs_core.export_sbml_dfs()
     ontologies: set
         A set of ontologies used to match features to pathway species
+    feature_id_var: str, default=FEATURE_ID_VAR_DEFAULT
+        Variable in "formatted_edgelist" containing feature ids
+    verbose: bool, default=False
+        Whether to print verbose output
 
     Returns:
     edges_on_pathway: pd.DataFrame
@@ -146,7 +282,7 @@ def edgelist_to_pathway_species(
         .drop_duplicates()
         .reset_index(drop=True)
         .to_frame()
-        .rename({0: "feature_id"}, axis=1)
+        .rename({0: feature_id_var}, axis=1)
     )
 
     # merge edgelist identifiers with pathway identifiers to map s_ids to identifiers
@@ -154,7 +290,8 @@ def edgelist_to_pathway_species(
         feature_identifiers=distinct_identifiers,
         species_identifiers=species_identifiers,
         ontologies=ontologies,
-        feature_id_var="feature_id",
+        feature_identifiers_var=feature_id_var,
+        verbose=verbose,
     )
 
     # add s_ids of both upstream and downstream edges to pathway
@@ -179,6 +316,348 @@ def edgelist_to_pathway_species(
     return edges_on_pathway
 
 
+def match_features_to_wide_pathway_species(
+    wide_df: pd.DataFrame,
+    species_identifiers: pd.DataFrame,
+    ontologies: Optional[Union[Set[str], Dict[str, str]]] = None,
+    feature_identifiers_var: str = IDENTIFIERS.IDENTIFIER,
+    feature_id_var: str = FEATURE_ID_VAR_DEFAULT,
+    verbose: bool = False,
+) -> pd.DataFrame:
+    """
+    Convert a wide-format DataFrame with multiple ontology columns to long format,
+    and match features to pathway species by ontology and identifier.
+
+    Parameters
+    ----------
+    wide_df : pd.DataFrame
+        DataFrame with ontology identifier columns and any number of results columns.
+        All non-ontology columns are treated as results.
+    species_identifiers : pd.DataFrame
+        DataFrame as required by features_to_pathway_species
+    ontologies : Optional[Union[Set[str], Dict[str, str]]], default=None
+        Either:
+        - Set of columns to treat as ontologies (these should be entries in ONTOLOGIES_LIST )
+        - Dict mapping wide column names to ontology names in the ONTOLOGIES_LIST controlled vocabulary
+        - None to automatically detect valid ontology columns based on ONTOLOGIES_LIST
+    feature_identifiers_var : str, default="identifier"
+        Name for the identifier column in the long format
+    feature_id_var: str, default=FEATURE_ID_VAR_DEFAULT
+        Name for the feature id column in the long format
+    verbose : bool, default=False
+        Whether to print verbose output
+
+    Returns
+    -------
+    pd.DataFrame
+        Output of match_by_ontology_and_identifier
+
+    Examples
+    --------
+    >>> # Example with auto-detected ontology columns and multiple results
+    >>> wide_df = pd.DataFrame({
+    ...     'uniprot': ['P12345', 'Q67890'],
+    ...     'chebi': ['15377', '16810'],
+    ...     'log2fc': [1.0, 2.0],
+    ...     'pvalue': [0.01, 0.05]
+    ... })
+    >>> result = match_features_to_wide_pathway_species(
+    ...     wide_df=wide_df,
+    ...     species_identifiers=species_identifiers
+    ... )
+
+    >>> # Example with custom ontology mapping
+    >>> wide_df = pd.DataFrame({
+    ...     'protein_id': ['P12345', 'Q67890'],
+    ...     'compound_id': ['15377', '16810'],
+    ...     'expression': [1.0, 2.0],
+    ...     'confidence': [0.8, 0.9]
+    ... })
+    >>> result = match_features_to_wide_pathway_species(
+    ...     wide_df=wide_df,
+    ...     species_identifiers=species_identifiers,
+    ...     ontologies={'protein_id': 'uniprot', 'compound_id': 'chebi'}
+    ... )
+    """
+    # Make a copy to avoid modifying the input
+    wide_df = wide_df.copy()
+
+    # Validate ontologies and get the set of ontology columns
+    ontology_cols = _validate_wide_ontologies(wide_df, ontologies)
+    melt_cols = list(ontology_cols)
+
+    # Apply renaming if a mapping is provided
+    if isinstance(ontologies, dict):
+        wide_df = wide_df.rename(columns=ontologies)
+
+    # Ensure feature_id column exists
+    wide_df = _ensure_feature_id_var(wide_df, feature_id_var)
+
+    # All non-ontology columns are treated as results
+    results_cols = list(set(wide_df.columns) - set(melt_cols))
+    if not results_cols:
+        raise ValueError("No results columns found in DataFrame")
+
+    logger.info(f"Using columns as results: {results_cols}")
+
+    # Melt ontology columns to long format, keeping all results columns
+    long_df = wide_df.melt(
+        id_vars=results_cols,
+        value_vars=melt_cols,
+        var_name=IDENTIFIERS.ONTOLOGY,
+        value_name=feature_identifiers_var,
+    ).dropna(subset=[feature_identifiers_var])
+
+    logger.debug(f"Final long format shape: {long_df.shape}")
+
+    # Call the matching function with the validated ontologies
+    out = match_by_ontology_and_identifier(
+        feature_identifiers=long_df,
+        species_identifiers=species_identifiers,
+        ontologies=ontology_cols,
+        feature_identifiers_var=feature_identifiers_var,
+    )
+
+    if verbose:
+        _log_feature_species_mapping_stats(out, feature_id_var)
+
+    return out
+
+
+def match_by_ontology_and_identifier(
+    feature_identifiers: pd.DataFrame,
+    species_identifiers: pd.DataFrame,
+    ontologies: Union[str, Set[str], List[str]],
+    feature_identifiers_var: str = IDENTIFIERS.IDENTIFIER,
+    verbose: bool = False,
+) -> pd.DataFrame:
+    """
+    Match features to pathway species based on both ontology and identifier matches.
+    Performs separate matching for each ontology and concatenates the results.
+
+    Parameters
+    ----------
+    feature_identifiers : pd.DataFrame
+        DataFrame containing feature identifiers and results.
+        Must have columns [ontology, feature_identifiers_var, results]
+    species_identifiers : pd.DataFrame
+        DataFrame containing species identifiers from pathway.
+        Must have columns [ontology, identifier]
+    ontologies : Union[str, Set[str], List[str]]
+        Ontologies to match on. Can be:
+        - A single ontology string
+        - A set of ontology strings
+        - A list of ontology strings
+    feature_identifiers_var : str, default="identifier"
+        Name of the identifier column in feature_identifiers
+    verbose : bool, default=False
+        Whether to print verbose output
+
+    Returns
+    -------
+    pd.DataFrame
+        Concatenated results of matching for each ontology.
+        Contains all columns from features_to_pathway_species()
+
+    Examples
+    --------
+    >>> # Match using a single ontology
+    >>> result = match_by_ontology_and_identifier(
+    ...     feature_identifiers=features_df,
+    ...     species_identifiers=species_df,
+    ...     ontologies="uniprot"
+    ... )
+
+    >>> # Match using multiple ontologies
+    >>> result = match_by_ontology_and_identifier(
+    ...     feature_identifiers=features_df,
+    ...     species_identifiers=species_df,
+    ...     ontologies={"uniprot", "chebi"}
+    ... )
+    """
+    # Convert string to set for consistent handling
+    if isinstance(ontologies, str):
+        ontologies = {ontologies}
+    elif isinstance(ontologies, list):
+        ontologies = set(ontologies)
+
+    # Validate ontologies
+    invalid_onts = ontologies - set(ONTOLOGIES_LIST)
+    if invalid_onts:
+        raise ValueError(
+            f"Invalid ontologies specified: {invalid_onts}. Must be one of: {ONTOLOGIES_LIST}"
+        )
+
+    # Initialize list to store results
+    matched_dfs = []
+
+    # Process each ontology separately
+    for ont in ontologies:
+        # Filter feature identifiers to current ontology and drop ontology column
+        ont_features = (
+            feature_identifiers[feature_identifiers[IDENTIFIERS.ONTOLOGY] == ont]
+            .drop(columns=[IDENTIFIERS.ONTOLOGY])
+            .copy()
+        )
+
+        if ont_features.empty:
+            logger.warning(f"No features found for ontology: {ont}")
+            continue
+
+        # Filter species identifiers to current ontology
+        ont_species = species_identifiers[
+            species_identifiers[IDENTIFIERS.ONTOLOGY] == ont
+        ].copy()
+
+        if ont_species.empty:
+            logger.warning(f"No species found for ontology: {ont}")
+            continue
+
+        logger.debug(
+            f"Matching {len(ont_features)} features to {len(ont_species)} species for ontology {ont}"
+        )
+
+        # Match features to species for this ontology
+        matched = features_to_pathway_species(
+            feature_identifiers=ont_features,
+            species_identifiers=ont_species,
+            ontologies={ont},
+            feature_identifiers_var=feature_identifiers_var,
+            verbose=verbose,
+        )
+
+        if matched.empty:
+            logger.warning(f"No matches found for ontology: {ont}")
+            continue
+
+        matched_dfs.append(matched)
+
+    if not matched_dfs:
+        logger.warning("No matches found for any ontology")
+        return pd.DataFrame()  # Return empty DataFrame with correct columns
+
+    # Combine results from all ontologies
+    result = pd.concat(matched_dfs, axis=0, ignore_index=True)
+
+    logger.info(
+        f"Found {len(result)} total matches across {len(matched_dfs)} ontologies"
+    )
+
+    return result
+
+
+def resolve_matches(
+    matched_data: pd.DataFrame,
+    feature_id_var: str = FEATURE_ID_VAR_DEFAULT,
+    index_col: str = SBML_DFS.S_ID,
+    numeric_agg: str = RESOLVE_MATCHES_AGGREGATORS.WEIGHTED_MEAN,
+    keep_id_col: bool = True,
+) -> pd.DataFrame:
+    """
+    Resolve many-to-1 and 1-to-many matches in matched data.
+
+    Parameters
+    ----------
+    matched_data : pd.DataFrame
+        DataFrame containing matched data with columns:
+        - feature_id_var: identifier column (e.g. feature_id)
+        - index_col: index column (e.g. s_id)
+        - other columns: data columns to be aggregated
+    feature_id_var : str, default="feature_id"
+        Name of the identifier column
+    index_col : str, default="s_id"
+        Name of the column to use as index
+    numeric_agg : str, default="weighted_mean"
+        Method to aggregate numeric columns:
+        - "weighted_mean": weighted by inverse of feature_id frequency (default)
+        - "mean": simple arithmetic mean
+        - "first": first value after sorting by feature_id_var (requires feature_id_var)
+        - "max": maximum value
+    keep_id_col : bool, default=True
+        Whether to keep and rollup the feature_id_var in the output.
+        If False, feature_id_var will be dropped from the output.
+
+    Returns
+    -------
+    pd.DataFrame
+        DataFrame with resolved matches:
+        - Many-to-1: numeric columns are aggregated using specified method
+        - 1-to-many: adds a count column showing number of matches
+        - Index is set to index_col and named accordingly
+
+    Raises
+    ------
+    KeyError
+        If feature_id_var is not present in the DataFrame
+    TypeError
+        If DataFrame contains unsupported data types (boolean or datetime)
+    """
+    # Make a copy to avoid modifying input
+    df = matched_data.copy()
+
+    # Check for unsupported data types
+    unsupported_dtypes = df.select_dtypes(include=["bool", "datetime64"]).columns
+    if not unsupported_dtypes.empty:
+        raise TypeError(
+            f"Unsupported data types found in columns: {list(unsupported_dtypes)}. "
+            "Boolean and datetime columns are not supported."
+        )
+
+    # Always require feature_id_var
+    if feature_id_var not in df.columns:
+        raise KeyError(feature_id_var)
+
+    # Deduplicate by feature_id within each s_id using groupby and first BEFORE any further processing
+    df = df.groupby([index_col, feature_id_var], sort=False).first().reset_index()
+
+    # Use a unique temporary column name for weights
+    if RESOLVE_MATCHES_TMP_WEIGHT_COL in df.columns:
+        raise ValueError(
+            f"Temporary weight column name '{RESOLVE_MATCHES_TMP_WEIGHT_COL}' already exists in the input data. Please rename or remove this column and try again."
+        )
+
+    # Calculate weights if needed (after deduplication!)
+    if numeric_agg == RESOLVE_MATCHES_AGGREGATORS.WEIGHTED_MEAN:
+        feature_counts = df[feature_id_var].value_counts()
+        df[RESOLVE_MATCHES_TMP_WEIGHT_COL] = (
+            1 / feature_counts[df[feature_id_var]].values
+        )
+
+    # Set index for grouping
+    df = df.set_index(index_col)
+
+    # Use utility to split columns
+    always_non_numeric = [feature_id_var] if keep_id_col else []
+    numeric_cols, non_numeric_cols = _split_numeric_non_numeric_columns(
+        df, always_non_numeric=always_non_numeric
+    )
+
+    # Get aggregator function
+    numeric_aggregator = _get_numeric_aggregator(
+        method=numeric_agg, feature_id_var=feature_id_var
+    )
+    resolved = _aggregate_grouped_columns(
+        df,
+        numeric_cols,
+        non_numeric_cols,
+        numeric_aggregator,
+        feature_id_var=feature_id_var,
+        numeric_agg=numeric_agg,
+    )
+    # Add count of matches per feature_id
+    match_counts = matched_data.groupby(index_col)[feature_id_var].nunique()
+    resolved[f"{feature_id_var}_match_count"] = match_counts
+
+    # Drop feature_id_var if not keeping it
+    if not keep_id_col and feature_id_var in resolved.columns:
+        resolved = resolved.drop(columns=[feature_id_var])
+
+    # Ensure index is named consistently
+    resolved.index.name = index_col
+
+    return resolved
+
+
 def edgelist_to_scids(
     formatted_edgelist: pd.DataFrame,
     sbml_dfs: sbml_dfs_core.SBML_dfs,
@@ -210,7 +689,7 @@ def edgelist_to_scids(
         downstream species mapped to "sc_id_downstream"
     """
 
-    _check_species_identifiers_table(species_identifiers)
+    identifiers._check_species_identifiers_table(species_identifiers)
 
     # map edges onto pathway entities based on shared identifiers
     edges_on_pathway = edgelist_to_pathway_species(
@@ -294,7 +773,7 @@ def filter_to_direct_mechanistic_interactions(
     )
 
     # reduce to distinct sc_id pairs
-    sc_id_pairs = edgelist_w_scids[CPR_EDGELIST_REQ_VARS].drop_duplicates()
+    sc_id_pairs = edgelist_w_scids[list(CPR_EDGELIST_REQ_VARS)].drop_duplicates()
 
     # define all existing direct regulatory interactions
     pathway_interactions = pd.concat(
@@ -568,7 +1047,7 @@ def _edgelist_to_scids_if_needed(
     else:
         utils.match_pd_vars(edgelist, IDENTIFIER_EDGELIST_REQ_VARS).assert_present()
 
-        _check_species_identifiers_table(species_identifiers)
+        identifiers._check_species_identifiers_table(species_identifiers)
 
         edgelist_w_scids = edgelist_to_scids(
             edgelist,
@@ -580,18 +1059,295 @@ def _edgelist_to_scids_if_needed(
         return edgelist_w_scids
 
 
-def _check_species_identifiers_table(
-    species_identifiers: pd.DataFrame,
-    required_vars: set = SPECIES_IDENTIFIERS_REQUIRED_VARS,
+def _validate_wide_ontologies(
+    wide_df: pd.DataFrame,
+    ontologies: Optional[Union[str, Set[str], Dict[str, str]]] = None,
+) -> Set[str]:
+    """
+    Validate ontology specifications against the wide DataFrame and ONTOLOGIES_LIST.
+
+    Parameters
+    ----------
+    wide_df : pd.DataFrame
+        DataFrame with one column per ontology and a results column
+    ontologies : Optional[Union[str, Set[str], Dict[str, str]]]
+        Either:
+        - String specifying a single ontology column
+        - Set of columns to treat as ontologies
+        - Dict mapping wide column names to ontology names
+        - None to automatically detect ontology columns based on ONTOLOGIES_LIST
+
+    Returns
+    -------
+    Set[str]
+        Set of validated ontology names. For dictionary mappings, returns the target ontology names.
+
+    Raises
+    ------
+    ValueError
+        If validation fails for any ontology specification or no valid ontologies are found
+    """
+    # Convert string input to set
+    if isinstance(ontologies, str):
+        ontologies = {ontologies}
+
+    # Get the set of ontology columns
+    if isinstance(ontologies, dict):
+        # Check source columns exist in DataFrame
+        missing_cols = set(ontologies.keys()) - set(wide_df.columns)
+        if missing_cols:
+            raise ValueError(f"Source columns not found in DataFrame: {missing_cols}")
+        # Validate target ontologies against ONTOLOGIES_LIST
+        invalid_onts = set(ontologies.values()) - set(ONTOLOGIES_LIST)
+        if invalid_onts:
+            raise ValueError(
+                f"Invalid ontologies in mapping: {invalid_onts}. Must be one of: {ONTOLOGIES_LIST}"
+            )
+        # Return target ontology names instead of source column names
+        ontology_cols = set(ontologies.values())
+
+    elif isinstance(ontologies, set):
+        # Check specified columns exist in DataFrame
+        missing_cols = ontologies - set(wide_df.columns)
+        if missing_cols:
+            raise ValueError(
+                f"Specified ontology columns not found in DataFrame: {missing_cols}"
+            )
+        # Validate specified ontologies against ONTOLOGIES_LIST
+        invalid_onts = ontologies - set(ONTOLOGIES_LIST)
+        if invalid_onts:
+            raise ValueError(
+                f"Invalid ontologies in set: {invalid_onts}. Must be one of: {ONTOLOGIES_LIST}"
+            )
+        ontology_cols = ontologies
+
+    else:
+        # Auto-detect ontology columns by matching against ONTOLOGIES_LIST
+        ontology_cols = set(wide_df.columns) & set(ONTOLOGIES_LIST)
+        if not ontology_cols:
+            raise ValueError(
+                f"No valid ontology columns found in DataFrame. Column names must match one of: {ONTOLOGIES_LIST}"
+            )
+        logger.info(f"Auto-detected ontology columns: {ontology_cols}")
+
+    logger.debug(f"Validated ontology columns: {ontology_cols}")
+    return ontology_cols
+
+
+def _ensure_feature_id_var(
+    df: pd.DataFrame, feature_id_var: str = FEATURE_ID_VAR_DEFAULT
+) -> pd.DataFrame:
+    """
+    Ensure the DataFrame has a feature_id column, creating one if it doesn't exist.
+
+    Parameters
+    ----------
+    df : pd.DataFrame
+        DataFrame to check/modify
+    feature_id_var : str, default=FEATURE_ID_VAR_DEFAULT
+        Name of the feature ID column
+
+    Returns
+    -------
+    pd.DataFrame
+        DataFrame with guaranteed feature_id column
+    """
+    if feature_id_var not in df.columns:
+        logger.warning(f"No {feature_id_var} column found in DataFrame, creating one")
+        df = df.copy()
+        df[feature_id_var] = np.arange(len(df))
+    return df
+
+
+def _get_numeric_aggregator(
+    method: str = RESOLVE_MATCHES_AGGREGATORS.WEIGHTED_MEAN,
+    feature_id_var: str = FEATURE_ID_VAR_DEFAULT,
+) -> callable:
+    """
+    Get aggregation function for numeric columns with various methods.
+
+    Parameters
+    ----------
+    method : str, default="weighted_mean"
+        Aggregation method to use:
+        - "weighted_mean": weighted by inverse of feature_id frequency (default)
+        - "mean": simple arithmetic mean
+        - "first": first value after sorting by feature_id_var (requires feature_id_var)
+        - "max": maximum value
+    feature_id_var : str, default="feature_id"
+        Name of the column specifying a measured feature - used for sorting and weighting
+
+    Returns
+    -------
+    callable
+        Aggregation function to use with groupby
+
+    Raises
+    ------
+    ValueError
+        If method is not recognized
+    """
+
+    def weighted_mean(df: pd.DataFrame) -> float:
+        # Get values and weights for this group
+        values = df["value"]
+        weights = df["weight"]
+        # Weights are already normalized globally, just use them directly
+        return (values * weights).sum() / weights.sum()
+
+    def first_by_id(df: pd.DataFrame) -> float:
+        # Sort by feature_id and take first value
+        return df.sort_values(feature_id_var).iloc[0]["value"]
+
+    def simple_mean(series: pd.Series) -> float:
+        return series.mean()
+
+    def simple_max(series: pd.Series) -> float:
+        return series.max()
+
+    aggregators = {
+        RESOLVE_MATCHES_AGGREGATORS.WEIGHTED_MEAN: weighted_mean,
+        RESOLVE_MATCHES_AGGREGATORS.MEAN: simple_mean,
+        RESOLVE_MATCHES_AGGREGATORS.FIRST: first_by_id,
+        RESOLVE_MATCHES_AGGREGATORS.MAX: simple_max,
+    }
+
+    if method not in aggregators:
+        raise ValueError(
+            f"Unknown aggregation method: {method}. Must be one of {list(aggregators.keys())}"
+        )
+
+    return aggregators[method]
+
+
+def _split_numeric_non_numeric_columns(df: pd.DataFrame, always_non_numeric=None):
+    """
+    Utility to split DataFrame columns into numeric and non-numeric, always treating specified columns as non-numeric.
+
+    Parameters
+    ----------
+    df : pd.DataFrame
+        The DataFrame to split.
+    always_non_numeric : list or set, optional
+        Columns to always treat as non-numeric (e.g., ['feature_id']).
+
+    Returns
+    -------
+    numeric_cols : pd.Index
+        Columns considered numeric (int64, float64, and not in always_non_numeric).
+    non_numeric_cols : pd.Index
+        Columns considered non-numeric (object, string, etc., plus always_non_numeric).
+    """
+    if always_non_numeric is None:
+        always_non_numeric = []
+    always_non_numeric = set(always_non_numeric)
+    numeric_cols = df.select_dtypes(include=["int64", "float64"]).columns.difference(
+        always_non_numeric
+    )
+    non_numeric_cols = df.columns.difference(numeric_cols)
+    return numeric_cols, non_numeric_cols
+
+
+def _aggregate_grouped_columns(
+    df: pd.DataFrame,
+    numeric_cols,
+    non_numeric_cols,
+    numeric_aggregator,
+    feature_id_var: str = FEATURE_ID_VAR_DEFAULT,
+    numeric_agg: str = RESOLVE_MATCHES_AGGREGATORS.WEIGHTED_MEAN,
+) -> pd.DataFrame:
+    """
+    Aggregate numeric and non-numeric columns for grouped DataFrame.
+    Assumes deduplication by feature_id within each s_id has already been performed.
+    Returns the combined DataFrame.
+    """
+    results = []
+
+    # Handle non-numeric columns
+    if len(non_numeric_cols) > 0:
+        non_numeric_agg = (
+            df[non_numeric_cols]
+            .groupby(level=0)
+            .agg(lambda x: ",".join(sorted(set(x.astype(str)))))
+        )
+        results.append(non_numeric_agg)
+    # Handle numeric columns
+    if len(numeric_cols) > 0:
+        numeric_results = {}
+        for col in numeric_cols:
+            if numeric_agg in [
+                RESOLVE_MATCHES_AGGREGATORS.FIRST,
+                RESOLVE_MATCHES_AGGREGATORS.WEIGHTED_MEAN,
+            ]:
+                agg_df = pd.DataFrame(
+                    {"value": df[col], feature_id_var: df[feature_id_var]}
+                )
+                if numeric_agg == RESOLVE_MATCHES_AGGREGATORS.WEIGHTED_MEAN:
+                    agg_df[RESOLVE_MATCHES_TMP_WEIGHT_COL] = df[
+                        RESOLVE_MATCHES_TMP_WEIGHT_COL
+                    ]
+                numeric_results[col] = agg_df.groupby(level=0).apply(
+                    lambda x: (
+                        numeric_aggregator(x)
+                        if numeric_agg != RESOLVE_MATCHES_AGGREGATORS.WEIGHTED_MEAN
+                        else numeric_aggregator(
+                            x.rename(columns={RESOLVE_MATCHES_TMP_WEIGHT_COL: "weight"})
+                        )
+                    )
+                )
+            else:
+                numeric_results[col] = df[col].groupby(level=0).agg(numeric_aggregator)
+        numeric_agg_df = pd.DataFrame(numeric_results)
+        results.append(numeric_agg_df)
+    # Combine results
+    if results:
+        resolved = pd.concat(results, axis=1)
+    else:
+        resolved = pd.DataFrame(index=df.index)
+    return resolved
+
+
+def _log_feature_species_mapping_stats(
+    pathway_species: pd.DataFrame, feature_id_var: str = FEATURE_ID_VAR_DEFAULT
 ):
-    missing_required_vars = required_vars.difference(
-        set(species_identifiers.columns.tolist())
+    """
+    Log statistics about the mapping between feature_id and s_id in the pathway_species DataFrame.
+    """
+
+    # Percent of feature_ids present one or more times in the output
+    n_feature_ids = pathway_species[feature_id_var].nunique()
+    n_input_feature_ids = (
+        pathway_species[feature_id_var].max() + 1
+        if feature_id_var in pathway_species.columns
+        else 0
     )
-    if len(missing_required_vars) > 0:
-        raise ValueError(
-            f"{len(missing_required_vars)} required variables "
-            "were missing from the species_identifiers table: "
-            f"{', '.join(missing_required_vars)}"
+    percent_present = (
+        100 * n_feature_ids / n_input_feature_ids if n_input_feature_ids else 0
+    )
+    logger.info(
+        f"{percent_present:.1f}% of feature_ids are present one or more times in the output ({n_feature_ids}/{n_input_feature_ids})"
+    )
+
+    # Number of times an s_id maps to 1+ feature_ids (with s_name)
+    s_id_counts = pathway_species.groupby(SBML_DFS.S_ID)[feature_id_var].nunique()
+    s_id_multi = s_id_counts[s_id_counts > 1]
+    logger.info(f"{len(s_id_multi)} s_id(s) map to more than one feature_id.")
+    if not s_id_multi.empty:
+        examples = pathway_species[
+            pathway_species[SBML_DFS.S_ID].isin(s_id_multi.index)
+        ][[SBML_DFS.S_ID, SBML_DFS.S_NAME, feature_id_var]]
+        logger.info(
+            f"Examples of s_id mapping to multiple feature_ids (showing up to 3):\n{examples.groupby([SBML_DFS.S_ID, SBML_DFS.S_NAME])[feature_id_var].apply(list).head(3)}"
         )
 
-    return None
+    # Number of times a feature_id maps to 1+ s_ids (with s_name)
+    feature_id_counts = pathway_species.groupby(feature_id_var)[SBML_DFS.S_ID].nunique()
+    feature_id_multi = feature_id_counts[feature_id_counts > 1]
+    logger.info(f"{len(feature_id_multi)} feature_id(s) map to more than one s_id.")
+    if not feature_id_multi.empty:
+        examples = pathway_species[
+            pathway_species[feature_id_var].isin(feature_id_multi.index)
+        ][[feature_id_var, SBML_DFS.S_ID, SBML_DFS.S_NAME]]
+        logger.info(
+            f"Examples of feature_id mapping to multiple s_ids (showing up to 3):\n{examples.groupby([feature_id_var])[[SBML_DFS.S_ID, SBML_DFS.S_NAME]].apply(lambda df: list(df.itertuples(index=False, name=None))).head(3)}"
+        )