diff --git a/src/indra_cogex/client/__init__.py b/src/indra_cogex/client/__init__.py
new file mode 100644
index 000000000..bd65c7e6d
--- /dev/null
+++ b/src/indra_cogex/client/__init__.py
@@ -0,0 +1,5 @@
+"""INDRA CoGEx Client."""
+
+from .neo4j_client import *
+from .queries import *
+from .subnetwork import *
diff --git a/src/indra_cogex/client/enrichment/discrete_weighted.py b/src/indra_cogex/client/enrichment/discrete_weighted.py
new file mode 100644
index 000000000..4bd736107
--- /dev/null
+++ b/src/indra_cogex/client/enrichment/discrete_weighted.py
@@ -0,0 +1,223 @@
+# -*- coding: utf-8 -*-
+
+"""Weighted ORA."""
+
+import pickle
+from typing import Iterable, Mapping, Optional, Set, Tuple
+
+import numpy as np
+import pandas as pd
+import pystow
+from scipy.stats import fisher_exact
+from statsmodels.stats.multitest import multipletests
+from tqdm.auto import tqdm
+
+from .utils import get_wikipathways
+from ..neo4j_client import Neo4jClient, autoclient
+
+__all__ = [
+    "get_weighted_contingency",
+    "get_lookup",
+    "get_gene_universe",
+    # Pathway database functions
+    "wikipathways_weighted_downstream_ora",
+    "wikipathways_weighted_upstream_ora",
+]
+
+LOOKUP_CACHE_PATH = pystow.join("indra", name="weighted_ora_belief_cache.tsv")
+LOOKUP_DICT_PATH = pystow.join("indra", name="weighted_ora_belief_cache.pkl")
+
+ALL_BELIEFS_CYPHER = """\
+MATCH (h:BioEntity)-[r:indra_rel]->(t:BioEntity)
+WHERE
+    h.id STARTS WITH "hgnc"                  // Collecting human genes only
+    AND t.id STARTS WITH "hgnc"
+    AND r.stmt_type <> "Complex"             // Ignore complexes since they are non-directional
+RETURN DISTINCT
+    h.id, t.id, r.stmt_hash, r.belief
+"""
+
+ALL_GENES_CYPHER = """\
+MATCH (n:BioEntity)
+WHERE n.id STARTS WITH 'hgnc'
+RETURN n.id
+"""
+
+
+@autoclient(cache=True, maxsize=1)
+def get_lookup(
+    *, client: Neo4jClient, force: bool = False
+) -> Mapping[Tuple[str, str], float]:
+    """Get the source/target to belief lookup table."""
+    if LOOKUP_DICT_PATH.is_file() and not force:
+        return pickle.loads(LOOKUP_DICT_PATH.read_bytes())
+    if LOOKUP_CACHE_PATH.is_file() and not force:
+        df = pd.read_csv(LOOKUP_CACHE_PATH, sep="\t")
+    else:
+        res = client.query_tx(all_beliefs)
+        df = pd.DataFrame(res, columns=["source", "target", "stmt_hash", "belief"])
+        df.to_csv(LOOKUP_CACHE_PATH, sep="\t", index=False)
+    rv = df.groupby(["source", "target"])["belief"].max().to_dict()
+    LOOKUP_DICT_PATH.write_bytes(pickle.dumps(rv))
+    return rv
+
+
+@autoclient(cache=True, maxsize=1)
+def get_gene_universe(*, client: Neo4jClient) -> Set[str]:
+    return {row[0] for row in client.query_tx(ALL_GENES_CYPHER)}
+
+
+def get_weighted_contingency(
+    query_gene_set: Set[str],
+    pathway_gene_set: Set[str],
+    universe: Set[str],  # all gene CURIEs
+    lookup: Mapping[Tuple[str, str], float],
+    query_is_source: bool = True,
+) -> np.ndarray:
+    a_11, a_12, a_21, a_22 = 0.0, 0.0, 0.0, 0.0
+
+    for gene in universe:
+        # TODO could also use mean or median
+        query_v = np.max(
+            [
+                lookup.get(
+                    (query_gene, gene) if query_is_source else (gene, query_gene), 0.0
+                )
+                for query_gene in query_gene_set
+            ]
+        )
+        m_query_v = 1.0 - query_v
+
+        if gene in pathway_gene_set:
+            pathway_v = 1.0
+            m_pathway_v = 0.0
+        else:
+            pathway_v = 0.0
+            m_pathway_v = 1.0
+
+        a_11 += query_v * pathway_v
+        a_12 += query_v * m_pathway_v
+        a_21 += m_query_v * pathway_v
+        a_22 += m_query_v * m_pathway_v
+
+    return np.array([[a_11, a_12], [a_21, a_22]])
+
+
+def _do_weighted_ora(
+    *,
+    curie_to_hgnc_ids: Mapping[Tuple[str, str], Set[str]],
+    gene_ids: Iterable[str],
+    universe: Set[str],
+    lookup: Mapping[Tuple[str, str], float],
+    method: Optional[str] = "fdr_bh",
+    alpha: Optional[float] = None,
+    keep_insignificant: bool = True,
+    query_is_source: bool = True,
+    use_tqdm: bool = True,
+) -> pd.DataFrame:
+    if alpha is None:
+        alpha = 0.05
+    query_gene_set = set(gene_ids)
+    rows = []
+
+    _tqdm_kwargs = dict(desc="Weighted ORA", unit="pathway", unit_scale=True)
+    it = tqdm(curie_to_hgnc_ids.items(), disable=not use_tqdm, **_tqdm_kwargs)
+    for (curie, name), pathway_hgnc_ids in it:
+        table = get_weighted_contingency(
+            query_gene_set=query_gene_set,
+            pathway_gene_set=pathway_hgnc_ids,
+            universe=universe,
+            query_is_source=query_is_source,
+            lookup=lookup,
+        )
+        _, pvalue = fisher_exact(table, alternative="greater")
+        rows.append((curie, name, pvalue))
+    df = pd.DataFrame(rows, columns=["curie", "name", "p"]).sort_values(
+        "p", ascending=True
+    )
+    df["mlp"] = -np.log10(df["p"])
+    if method:
+        correction_results = multipletests(
+            df["p"],
+            method=method,
+            is_sorted=True,
+            alpha=alpha,
+        )
+        df["q"] = correction_results[1]
+        df["mlq"] = -np.log10(df["q"])
+        df = df.sort_values("q", ascending=True)
+    if not keep_insignificant:
+        df = df[df["q"] < alpha]
+    return df
+
+
+def _ora(func, query_is_source, client: Neo4jClient, **kwargs):
+    universe = get_gene_universe(client=client)
+    lookup = get_lookup(client=client)
+    return _do_weighted_ora(
+        curie_to_hgnc_ids=func(client=client),
+        query_is_source=query_is_source,
+        universe=universe,
+        lookup=lookup,
+        **kwargs,
+    )
+
+
+@autoclient()
+def wikipathways_weighted_upstream_ora(
+    gene_ids: Iterable[str], *, client: Neo4jClient, **kwargs
+) -> pd.DataFrame:
+    """Calculate weighted over-representation on all WikiPathway pathways.
+
+    Parameters
+    ----------
+    gene_ids :
+        List of gene identifiers
+    client :
+        Neo4jClient
+    **kwargs :
+        Additional keyword arguments to pass to _do_ora
+
+    Returns
+    -------
+    :
+        DataFrame with columns:
+        curie, name, p, q, mlp, mlq
+    """
+    return _ora(
+        func=get_wikipathways,
+        client=client,
+        query_is_source=True,
+        gene_ids=gene_ids,
+        **kwargs,
+    )
+
+
+@autoclient()
+def wikipathways_weighted_downstream_ora(
+    gene_ids: Iterable[str], *, client: Neo4jClient, **kwargs
+) -> pd.DataFrame:
+    """Calculate weighted over-representation on all WikiPathway pathways.
+
+    Parameters
+    ----------
+    gene_ids :
+        List of gene identifiers
+    client :
+        Neo4jClient
+    **kwargs :
+        Additional keyword arguments to pass to _do_ora
+
+    Returns
+    -------
+    :
+        DataFrame with columns:
+        curie, name, p, q, mlp, mlq
+    """
+    return _ora(
+        func=get_wikipathways,
+        client=client,
+        query_is_source=False,
+        gene_ids=gene_ids,
+        **kwargs,
+    )