@nahisaho/satori 0.12.0 → 0.13.0

package/src/.github/skills/scientific-pharmacology-targets/SKILL.md

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+---
+name: scientific-pharmacology-targets
+description: |
+  薬理学的ターゲットプロファイリングスキル。BindingDB 結合親和性、
+  GPCRdb GPCR 構造-活性、GtoPdb 薬理学、BRENDA 酵素動態、
+  Pharos 未解明ターゲット(TDL)の統合解析パイプライン。
+---
+
+# Scientific Pharmacology Targets
+
+複数の薬理学データベース (BindingDB, GPCRdb, GtoPdb, BRENDA, Pharos) を
+統合した包括的ターゲットプロファイリングパイプラインを提供する。
+
+## When to Use
+
+- 特定タンパク質の既知リガンド・結合親和性を調べるとき
+- GPCR のリガンド・変異・構造情報を取得するとき
+- 薬物-ターゲット相互作用のデータベース横断検索を行うとき
+- 酵素阻害剤データ (BRENDA) を調べるとき
+- 未解明ターゲット (Tdark/Tbio) のドラッガビリティを評価するとき
+
+---
+
+## Quick Start
+
+## 1. BindingDB 結合親和性データ取得
+
+```python
+import requests
+import pandas as pd
+
+
+def get_bindingdb_ligands(uniprot_id, cutoff=None):
+    """
+    BindingDB から UniProt ID ベースのリガンド結合データを取得。
+
+    Parameters:
+        uniprot_id: str — UniProt accession (e.g., "P00533")
+        cutoff: float | None — affinity cutoff nM
+
+    ToolUniverse:
+        BindingDB_get_ligands_by_uniprot(uniprot_id=uniprot_id)
+        BindingDB_get_targets_by_compound(smiles=smiles)
+    """
+    url = "https://bindingdb.org/axis2/services/BDBService"
+    params = {
+        "uniprot": uniprot_id,
+        "response": "json",
+    }
+    if cutoff:
+        params["cutoff"] = cutoff
+
+    resp = requests.get(f"{url}/getLigandsByUniprot", params=params)
+    resp.raise_for_status()
+    data = resp.json()
+
+    ligands = data.get("getLigandsByUniprotResponse", {}).get("affinities", [])
+    results = []
+    for lig in ligands:
+        results.append({
+            "monomer_id": lig.get("monomerid", ""),
+            "smiles": lig.get("smiles", ""),
+            "affinity_type": lig.get("affinity_type", ""),
+            "affinity_value_nm": lig.get("affinity", ""),
+            "source": lig.get("source", ""),
+        })
+
+    df = pd.DataFrame(results)
+    print(f"BindingDB '{uniprot_id}': {len(df)} ligands")
+    return df
+```
+
+## 2. GPCRdb GPCR プロファイリング
+
+```python
+def get_gpcrdb_profile(protein_entry):
+    """
+    GPCRdb から GPCR のリガンド・変異・構造情報を取得。
+
+    Parameters:
+        protein_entry: str — GPCRdb entry name (e.g., "adrb2_human")
+
+    ToolUniverse:
+        GPCRdb_get_protein(entry_name=protein_entry)
+        GPCRdb_get_ligands(entry_name=protein_entry)
+        GPCRdb_get_mutations(entry_name=protein_entry)
+        GPCRdb_get_structures(entry_name=protein_entry)
+        GPCRdb_list_proteins()
+    """
+    base = "https://gpcrdb.org/services"
+
+    # Protein info
+    resp_p = requests.get(f"{base}/protein/{protein_entry}/")
+    resp_p.raise_for_status()
+    protein = resp_p.json()
+
+    # Ligands
+    resp_l = requests.get(f"{base}/ligands/{protein_entry}/")
+    ligands = resp_l.json() if resp_l.status_code == 200 else []
+
+    # Mutations
+    resp_m = requests.get(f"{base}/mutants/{protein_entry}/")
+    mutations = resp_m.json() if resp_m.status_code == 200 else []
+
+    # Structures
+    resp_s = requests.get(f"{base}/structure/protein/{protein_entry}/")
+    structures = resp_s.json() if resp_s.status_code == 200 else []
+
+    profile = {
+        "entry_name": protein.get("entry_name", ""),
+        "name": protein.get("name", ""),
+        "family": protein.get("family", ""),
+        "species": protein.get("species", ""),
+        "num_ligands": len(ligands),
+        "num_mutations": len(mutations),
+        "num_structures": len(structures),
+    }
+
+    print(f"GPCRdb '{protein_entry}': "
+          f"{profile['num_ligands']} ligands, "
+          f"{profile['num_mutations']} mutations, "
+          f"{profile['num_structures']} structures")
+    return profile, ligands, mutations, structures
+```
+
+## 3. GtoPdb 薬理学データ
+
+```python
+def get_gtopdb_target_pharmacology(target_id):
+    """
+    Guide to PHARMACOLOGY (GtoPdb) から
+    ターゲットの薬理学的相互作用データを取得。
+
+    ToolUniverse:
+        GtoPdb_get_target(target_id=target_id)
+        GtoPdb_get_target_interactions(target_id=target_id)
+        GtoPdb_get_ligand(ligand_id=ligand_id)
+        GtoPdb_search_interactions(query=query)
+    """
+    base = "https://www.guidetopharmacology.org/services"
+
+    # Target info
+    resp_t = requests.get(f"{base}/targets/{target_id}")
+    resp_t.raise_for_status()
+    target = resp_t.json()
+
+    # Interactions
+    resp_i = requests.get(f"{base}/targets/{target_id}/interactions")
+    interactions = resp_i.json() if resp_i.status_code == 200 else []
+
+    results = []
+    for ix in interactions:
+        results.append({
+            "ligand_id": ix.get("ligandId", ""),
+            "ligand_name": ix.get("ligandName", ""),
+            "type": ix.get("type", ""),
+            "action": ix.get("action", ""),
+            "affinity_type": ix.get("affinityType", ""),
+            "affinity_median": ix.get("affinityMedian", ""),
+            "approved": ix.get("approvedDrug", False),
+        })
+
+    df = pd.DataFrame(results)
+    print(f"GtoPdb target {target_id} ({target.get('name', '')}): "
+          f"{len(df)} interactions")
+    return target, df
+```
+
+## 4. Pharos/TCRD 未解明ターゲット検索
+
+```python
+def search_pharos_targets(query, tdl=None):
+    """
+    Pharos / TCRD からターゲット情報を取得。
+    Target Development Level (TDL) でフィルタ可能。
+
+    Parameters:
+        query: str — gene symbol or target name
+        tdl: str | None — "Tclin", "Tchem", "Tbio", "Tdark"
+
+    ToolUniverse:
+        Pharos_search_targets(q=query)
+        Pharos_get_target(q=query)
+        Pharos_get_tdl_summary()
+        Pharos_get_disease_targets(disease_name=disease_name)
+    """
+    url = "https://pharos-api.ncats.io/graphql"
+    gql = """
+    query TargetSearch($term: String!, $top: Int) {
+        targets(filter: { term: $term }, top: $top) {
+            targets {
+                name
+                sym
+                uniprot { accession }
+                tdl
+                fam
+                novelty
+                jensenScore
+                diseaseCount
+                ligandCount
+            }
+            count
+        }
+    }
+    """
+    variables = {"term": query, "top": 20}
+    resp = requests.post(url, json={"query": gql, "variables": variables})
+    resp.raise_for_status()
+    data = resp.json()["data"]["targets"]
+
+    results = []
+    for t in data["targets"]:
+        results.append({
+            "symbol": t.get("sym", ""),
+            "name": t.get("name", ""),
+            "uniprot": t.get("uniprot", {}).get("accession", ""),
+            "tdl": t.get("tdl", ""),
+            "family": t.get("fam", ""),
+            "novelty": t.get("novelty", 0),
+            "disease_count": t.get("diseaseCount", 0),
+            "ligand_count": t.get("ligandCount", 0),
+        })
+
+    df = pd.DataFrame(results)
+    if tdl:
+        df = df[df["tdl"] == tdl]
+
+    print(f"Pharos '{query}': {len(df)} targets"
+          f"{f' (TDL={tdl})' if tdl else ''}")
+    return df
+```
+
+## 5. 統合ターゲットプロファイリング
+
+```python
+def integrated_target_profile(uniprot_id, gene_symbol):
+    """
+    複数データベースを統合したターゲットプロファイル。
+
+    ToolUniverse (横断):
+        BindingDB_get_ligands_by_uniprot(uniprot_id)
+        Pharos_get_target(q=gene_symbol)
+        GtoPdb_get_targets() → GtoPdb_get_target_interactions()
+    """
+    profile = {
+        "uniprot_id": uniprot_id,
+        "gene_symbol": gene_symbol,
+    }
+
+    # BindingDB ligands
+    try:
+        bdb_df = get_bindingdb_ligands(uniprot_id)
+        profile["bindingdb_ligand_count"] = len(bdb_df)
+    except Exception:
+        profile["bindingdb_ligand_count"] = 0
+
+    # Pharos TDL
+    try:
+        pharos_df = search_pharos_targets(gene_symbol)
+        if not pharos_df.empty:
+            row = pharos_df.iloc[0]
+            profile["tdl"] = row.get("tdl", "")
+            profile["novelty"] = row.get("novelty", 0)
+    except Exception:
+        profile["tdl"] = "Unknown"
+
+    print(f"Integrated profile {gene_symbol}: TDL={profile.get('tdl', '?')}, "
+          f"BindingDB={profile['bindingdb_ligand_count']} ligands")
+    return profile
+```
+
+## References
+
+### Output Files
+
+| ファイル | 形式 |
+|---|---|
+| `results/bindingdb_ligands.csv` | CSV |
+| `results/gpcrdb_profile.json` | JSON |
+| `results/gtopdb_interactions.csv` | CSV |
+| `results/pharos_targets.csv` | CSV |
+| `results/integrated_target_profile.json` | JSON |
+
+### 利用可能ツール
+
+| カテゴリ | 主要ツール | 用途 |
+|---|---|---|
+| BindingDB | `BindingDB_get_ligands_by_uniprot` | UniProt→リガンド |
+| BindingDB | `BindingDB_get_ligands_by_uniprots` | バッチ |
+| BindingDB | `BindingDB_get_ligands_by_pdb` | PDB→リガンド |
+| BindingDB | `BindingDB_get_targets_by_compound` | 化合物→ターゲット |
+| GPCRdb | `GPCRdb_get_protein` | GPCR 詳細 |
+| GPCRdb | `GPCRdb_get_ligands` | GPCR リガンド |
+| GPCRdb | `GPCRdb_get_mutations` | GPCR 変異 |
+| GPCRdb | `GPCRdb_get_structures` | GPCR 構造 |
+| GPCRdb | `GPCRdb_list_proteins` | GPCR 一覧 |
+| GtoPdb | `GtoPdb_get_target` | ターゲット情報 |
+| GtoPdb | `GtoPdb_get_target_interactions` | 相互作用 |
+| GtoPdb | `GtoPdb_get_ligand` | リガンド情報 |
+| GtoPdb | `GtoPdb_get_targets` | ターゲット一覧 |
+| GtoPdb | `GtoPdb_list_ligands` | リガンド一覧 |
+| GtoPdb | `GtoPdb_get_disease` | 疾患関連 |
+| GtoPdb | `GtoPdb_list_diseases` | 疾患一覧 |
+| GtoPdb | `GtoPdb_search_interactions` | 相互作用検索 |
+| BRENDA | `BRENDA_get_inhibitors` | 酵素阻害剤 |
+| Pharos | `Pharos_search_targets` | ターゲット検索 |
+| Pharos | `Pharos_get_target` | ターゲット詳細 |
+| Pharos | `Pharos_get_tdl_summary` | TDL サマリー |
+| Pharos | `Pharos_get_disease_targets` | 疾患→ターゲット |
+
+### 参照スキル
+
+| スキル | 関連 |
+|---|---|
+| `scientific-drug-target-interaction` | DTI 予測 |
+| `scientific-compound-similarity` | 化合物類似性 |
+| `scientific-compound-screening` | 化合物スクリーニング |
+| `scientific-molecular-docking` | 分子ドッキング |
+| `scientific-protein-interaction-network` | PPI ネットワーク |
+
+### 依存パッケージ
+
+`requests`, `pandas`

package/src/.github/skills/scientific-rare-disease-genetics/SKILL.md

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+---
+name: scientific-rare-disease-genetics
+description: |
+  希少疾患遺伝学スキル。OMIM 遺伝子-疾患マッピング、Orphanet 希少疾患
+  分類・遺伝子照会、DisGeNET 疾患-遺伝子関連スコア、IMPC マウス表現型
+  参照、遺伝子-表現型統合解析パイプライン。
+---
+
+# Scientific Rare Disease Genetics
+
+OMIM / Orphanet / DisGeNET / IMPC を統合した
+希少疾患遺伝学パイプラインを提供する。
+
+## When to Use
+
+- 希少疾患の原因遺伝子を同定するとき
+- OMIM で遺伝子-疾患の Mendelian 関連を調べるとき
+- Orphanet で希少疾患分類や有病率を検索するとき
+- DisGeNET で疾患-遺伝子関連スコア (GDA) を取得するとき
+- IMPC マウスノックアウト表現型と比較するとき
+
+---
+
+## Quick Start
+
+## 1. OMIM 遺伝子-疾患マッピング
+
+```python
+import requests
+import pandas as pd
+
+OMIM_API = "https://api.omim.org/api"
+
+
+def search_omim(query, api_key, include="geneMap"):
+    """
+    OMIM データベース検索。
+
+    Parameters:
+        query: str — 検索語 (遺伝子名、疾患名)
+        api_key: str — OMIM API キー
+        include: str — "geneMap", "clinicalSynopsis", "all"
+
+    ToolUniverse:
+        OMIM_search(query=query)
+        OMIM_get_entry(mim_number=mim_number)
+        OMIM_get_gene_map(gene_symbol=gene_symbol)
+        OMIM_get_clinical_synopsis(mim_number=mim_number)
+    """
+    params = {
+        "search": query,
+        "include": include,
+        "format": "json",
+        "apiKey": api_key,
+    }
+    resp = requests.get(f"{OMIM_API}/entry/search", params=params)
+    resp.raise_for_status()
+    data = resp.json()
+
+    entries = data.get("omim", {}).get("searchResponse", {}).get("entryList", [])
+    results = []
+    for entry in entries:
+        e = entry.get("entry", {})
+        gene_map = e.get("geneMap", {})
+        results.append({
+            "mim_number": e.get("mimNumber"),
+            "title": e.get("titles", {}).get("preferredTitle", ""),
+            "gene_symbols": gene_map.get("geneSymbols", ""),
+            "chromosome": gene_map.get("computedCytoLocation", ""),
+            "phenotypes": [
+                p.get("phenotype", "")
+                for p in gene_map.get("phenotypeMapList", [])
+            ],
+            "inheritance": [
+                p.get("phenotypeMappingKey", "")
+                for p in gene_map.get("phenotypeMapList", [])
+            ],
+        })
+
+    df = pd.DataFrame(results)
+    print(f"OMIM search '{query}': {len(df)} entries")
+    return df
+```
+
+## 2. Orphanet 希少疾患分類
+
+```python
+ORPHANET_API = "https://api.orphadata.com"
+
+
+def search_orphanet_diseases(query):
+    """
+    Orphanet 希少疾患検索。
+
+    ToolUniverse:
+        Orphanet_search_diseases(query=query)
+        Orphanet_search_by_name(name=query)
+        Orphanet_get_disease(orpha_code=code)
+        Orphanet_get_genes(orpha_code=code)
+        Orphanet_get_classification(orpha_code=code)
+    """
+    resp = requests.get(
+        f"{ORPHANET_API}/rd-cross-referencing",
+        params={"query": query}
+    )
+    resp.raise_for_status()
+    data = resp.json()
+
+    results = []
+    for item in data if isinstance(data, list) else [data]:
+        results.append({
+            "orpha_code": item.get("ORPHAcode", ""),
+            "name": item.get("Preferred term", ""),
+            "prevalence_class": item.get("Prevalence", {}).get("PrevalenceClass", ""),
+            "inheritance": item.get("TypeOfInheritance", []),
+            "age_of_onset": item.get("AgeOfOnset", []),
+            "genes": item.get("DisorderGeneAssociationList", []),
+        })
+
+    df = pd.DataFrame(results)
+    print(f"Orphanet search '{query}': {len(df)} diseases")
+    return df
+```
+
+## 3. DisGeNET 疾患-遺伝子関連スコア
+
+```python
+DISGENET_API = "https://www.disgenet.org/api"
+
+
+def get_disease_gene_associations(disease_id, api_key):
+    """
+    DisGeNET GDA スコアによる疾患-遺伝子関連取得。
+
+    Parameters:
+        disease_id: str — UMLS CUI (e.g., "C0023264") or disease name
+        api_key: str — DisGeNET API key
+
+    ToolUniverse:
+        DisGeNET_search_disease(query=disease_id)
+        DisGeNET_get_disease_genes(disease_id=disease_id)
+        DisGeNET_search_gene(query=gene)
+        DisGeNET_get_gene_diseases(gene_symbol=gene)
+        DisGeNET_get_variant_diseases(variant_id=variant)
+    """
+    headers = {"Authorization": f"Bearer {api_key}"}
+    resp = requests.get(
+        f"{DISGENET_API}/gda/disease/{disease_id}",
+        headers=headers
+    )
+    resp.raise_for_status()
+    data = resp.json()
+
+    results = []
+    for gda in data:
+        results.append({
+            "gene_symbol": gda.get("gene_symbol", ""),
+            "gene_id": gda.get("geneid", ""),
+            "gda_score": gda.get("score", 0),
+            "ei": gda.get("ei", 0),  # Evidence Index
+            "el": gda.get("el", ""),  # Evidence Level
+            "n_pmids": gda.get("pmid_count", 0),
+            "source": gda.get("source", ""),
+        })
+
+    df = pd.DataFrame(results)
+    if not df.empty:
+        df = df.sort_values("gda_score", ascending=False)
+
+    print(f"DisGeNET '{disease_id}': {len(df)} gene associations, "
+          f"top GDA score={df['gda_score'].max():.3f}" if len(df) > 0 else "")
+    return df
+```
+
+## 4. IMPC マウス表現型参照
+
+```python
+IMPC_API = "https://www.ebi.ac.uk/mi/impc/solr"
+
+
+def get_impc_mouse_phenotypes(gene_symbol):
+    """
+    IMPC マウスノックアウト表現型データ取得。
+
+    ToolUniverse:
+        IMPC_search_genes(query=gene_symbol)
+        IMPC_get_gene_summary(gene_symbol=gene_symbol)
+        IMPC_get_phenotypes_by_gene(gene_symbol=gene_symbol)
+        IMPC_get_gene_phenotype_hits(gene_symbol=gene_symbol)
+    """
+    params = {
+        "q": f"marker_symbol:{gene_symbol}",
+        "rows": 100,
+        "wt": "json",
+    }
+    resp = requests.get(f"{IMPC_API}/genotype-phenotype/select", params=params)
+    resp.raise_for_status()
+    data = resp.json()
+
+    results = []
+    for doc in data.get("response", {}).get("docs", []):
+        results.append({
+            "gene_symbol": doc.get("marker_symbol", ""),
+            "mp_term_id": doc.get("mp_term_id", ""),
+            "mp_term_name": doc.get("mp_term_name", ""),
+            "top_level_mp": doc.get("top_level_mp_term_name", []),
+            "p_value": doc.get("p_value", None),
+            "effect_size": doc.get("effect_size", None),
+            "zygosity": doc.get("zygosity", ""),
+            "procedure_name": doc.get("procedure_name", ""),
+        })
+
+    df = pd.DataFrame(results)
+    if not df.empty and "p_value" in df.columns:
+        df = df.sort_values("p_value")
+
+    print(f"IMPC '{gene_symbol}': {len(df)} phenotype associations")
+    return df
+```
+
+## 5. 遺伝子-表現型統合解析
+
+```python
+def rare_disease_gene_analysis(gene_symbol, omim_api_key=None,
+                                 disgenet_api_key=None):
+    """
+    全 DB 統合の希少疾患遺伝子プロファイリング。
+    """
+    profile = {"gene": gene_symbol, "sources": {}}
+
+    # 1. OMIM
+    if omim_api_key:
+        try:
+            omim_df = search_omim(gene_symbol, omim_api_key)
+            profile["sources"]["omim"] = {
+                "entries": len(omim_df),
+                "phenotypes": omim_df["phenotypes"].explode().dropna().unique().tolist()
+                    if not omim_df.empty else [],
+            }
+        except Exception as e:
+            profile["sources"]["omim"] = {"error": str(e)}
+
+    # 2. Orphanet
+    try:
+        orpha_df = search_orphanet_diseases(gene_symbol)
+        profile["sources"]["orphanet"] = {
+            "diseases": len(orpha_df),
+            "names": orpha_df["name"].tolist() if not orpha_df.empty else [],
+        }
+    except Exception as e:
+        profile["sources"]["orphanet"] = {"error": str(e)}
+
+    # 3. DisGeNET
+    if disgenet_api_key:
+        try:
+            dgn_df = get_disease_gene_associations(gene_symbol, disgenet_api_key)
+            profile["sources"]["disgenet"] = {
+                "associations": len(dgn_df),
+                "max_gda_score": float(dgn_df["gda_score"].max())
+                    if not dgn_df.empty else 0,
+            }
+        except Exception as e:
+            profile["sources"]["disgenet"] = {"error": str(e)}
+
+    # 4. IMPC
+    try:
+        impc_df = get_impc_mouse_phenotypes(gene_symbol)
+        profile["sources"]["impc"] = {
+            "phenotypes": len(impc_df),
+            "top_phenotypes": impc_df["mp_term_name"].head(5).tolist()
+                if not impc_df.empty else [],
+        }
+    except Exception as e:
+        profile["sources"]["impc"] = {"error": str(e)}
+
+    n_sources = sum(1 for v in profile["sources"].values() if "error" not in v)
+    print(f"Rare disease profile '{gene_symbol}': {n_sources}/4 sources OK")
+    return profile
+```
+
+## References
+
+### Output Files
+
+| ファイル | 形式 |
+|---|---|
+| `results/omim_search.csv` | CSV |
+| `results/orphanet_diseases.csv` | CSV |
+| `results/disgenet_gda.csv` | CSV |
+| `results/impc_phenotypes.csv` | CSV |
+| `results/rare_disease_profile.json` | JSON |
+
+### 利用可能ツール
+
+| カテゴリ | 主要ツール | 用途 |
+|---|---|---|
+| OMIM | `OMIM_search` | 遺伝子/疾患検索 |
+| OMIM | `OMIM_get_entry` | MIM エントリ取得 |
+| OMIM | `OMIM_get_gene_map` | 遺伝子マップ |
+| OMIM | `OMIM_get_clinical_synopsis` | 臨床概要 |
+| Orphanet | `Orphanet_search_diseases` | 希少疾患検索 |
+| Orphanet | `Orphanet_get_disease` | 疾患詳細 |
+| Orphanet | `Orphanet_get_genes` | 関連遺伝子 |
+| Orphanet | `Orphanet_get_classification` | 分類情報 |
+| Orphanet | `Orphanet_search_by_name` | 名前検索 |
+| DisGeNET | `DisGeNET_search_disease` | 疾患検索 |
+| DisGeNET | `DisGeNET_get_disease_genes` | 疾患遺伝子 |
+| DisGeNET | `DisGeNET_get_gene_diseases` | 遺伝子疾患 |
+| DisGeNET | `DisGeNET_get_variant_diseases` | バリアント疾患 |
+| IMPC | `IMPC_search_genes` | 遺伝子検索 |
+| IMPC | `IMPC_get_gene_summary` | 遺伝子サマリー |
+| IMPC | `IMPC_get_phenotypes_by_gene` | 表現型取得 |
+| IMPC | `IMPC_get_gene_phenotype_hits` | ヒット数 |
+
+### 参照スキル
+
+| スキル | 関連 |
+|---|---|
+| `scientific-disease-research` | GWAS/Orphanet 疾患研究 |
+| `scientific-variant-interpretation` | ACMG バリアント解釈 |
+| `scientific-variant-effect-prediction` | 病原性予測 |
+| `scientific-population-genetics` | 集団遺伝学 |
+| `scientific-human-protein-atlas` | タンパク質発現 |
+
+### 依存パッケージ
+
+`requests`, `pandas`