@nahisaho/satori 0.11.1 → 0.13.0

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

@@ -0,0 +1,323 @@
+---
+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-protein-domain-family/SKILL.md

@@ -0,0 +1,369 @@
+---
+name: scientific-protein-domain-family
+description: |
+  タンパク質ドメイン・ファミリー解析スキル。InterPro アノテーション検索、
+  InterProScan によるシーケンスベースドメイン予測、Pfam/SMART/CDD
+  ドメイン分類、ドメインアーキテクチャ可視化、ファミリー系統樹構築。
+---
+
+# Scientific Protein Domain & Family Analysis
+
+InterPro / InterProScan を中心としたタンパク質ドメイン解析
+およびファミリー分類パイプラインを提供する。
+
+## When to Use
+
+- 未知タンパク質のドメイン構成を同定するとき
+- InterPro/Pfam アノテーションでファミリー分類するとき
+- ドメインアーキテクチャを比較・可視化するとき
+- InterProScan でバッチシーケンス解析するとき
+- 進化的なドメイン保存性を評価するとき
+
+---
+
+## Quick Start
+
+## 1. InterPro ドメイン検索
+
+```python
+import requests
+import pandas as pd
+import json
+
+
+INTERPRO_API = "https://www.ebi.ac.uk/interpro/api"
+
+
+def search_interpro_domains(query, db_filter=None):
+    """
+    InterPro REST API でドメイン検索。
+
+    Parameters:
+        query: str — ドメイン名またはキーワード (e.g., "kinase", "SH3")
+        db_filter: str — "pfam", "smart", "cdd", "prosite" など
+
+    ToolUniverse:
+        InterPro_search_domains(query=query)
+    """
+    url = f"{INTERPRO_API}/entry/interpro"
+    params = {"search": query, "page_size": 25}
+
+    if db_filter:
+        url = f"{INTERPRO_API}/entry/{db_filter}"
+
+    resp = requests.get(url, params=params)
+    resp.raise_for_status()
+    data = resp.json()
+
+    results = []
+    for entry in data.get("results", []):
+        meta = entry.get("metadata", {})
+        results.append({
+            "accession": meta.get("accession", ""),
+            "name": meta.get("name", ""),
+            "type": meta.get("type", ""),
+            "source_database": meta.get("source_database", "interpro"),
+            "description": (meta.get("description", [{}])[0].get("text", "")[:200]
+                          if meta.get("description") else ""),
+            "member_databases": meta.get("member_databases", {}),
+        })
+
+    df = pd.DataFrame(results)
+    print(f"InterPro search '{query}': {len(df)} entries found")
+    return df
+```
+
+## 2. タンパク質のドメイン組成取得
+
+```python
+def get_protein_domains(uniprot_id):
+    """
+    UniProt タンパク質のドメインアノテーションを取得。
+
+    Parameters:
+        uniprot_id: str — UniProt accession (e.g., "P04637")
+
+    ToolUniverse:
+        InterPro_get_protein_domains(uniprot_id=uniprot_id)
+    """
+    url = f"{INTERPRO_API}/protein/uniprot/{uniprot_id}"
+    params = {"page_size": 50}
+
+    resp = requests.get(url, params=params)
+    resp.raise_for_status()
+    data = resp.json()
+
+    domains = []
+    for entry in data.get("results", []):
+        meta = entry.get("metadata", {})
+        # 各ドメインの位置情報
+        for protein_info in entry.get("proteins", []):
+            for loc in protein_info.get("entry_protein_locations", []):
+                for frag in loc.get("fragments", []):
+                    domains.append({
+                        "accession": meta.get("accession", ""),
+                        "name": meta.get("name", ""),
+                        "type": meta.get("type", ""),
+                        "start": frag.get("start", 0),
+                        "end": frag.get("end", 0),
+                        "source": meta.get("source_database", "interpro"),
+                    })
+
+    df = pd.DataFrame(domains)
+    if not df.empty:
+        df = df.sort_values("start").reset_index(drop=True)
+
+    print(f"Protein {uniprot_id}: {len(df)} domain annotations")
+    return df
+```
+
+## 3. InterProScan シーケンスベース予測
+
+```python
+import time
+
+
+IPRSCAN_API = "https://www.ebi.ac.uk/Tools/services/rest/iprscan5"
+
+
+def submit_interproscan(sequence, email="user@example.com",
+                          applications=None):
+    """
+    InterProScan REST API でシーケンスベースドメイン予測。
+
+    Parameters:
+        sequence: str — アミノ酸配列 (FASTA or raw)
+        email: str — 結果通知メール
+        applications: list — ["Pfam", "SMART", "CDD", "ProSitePatterns"]
+
+    ToolUniverse:
+        InterProScan_scan_sequence(sequence=sequence)
+        InterProScan_get_job_status(job_id=job_id)
+        InterProScan_get_job_results(job_id=job_id)
+    """
+    if applications is None:
+        applications = ["Pfam", "SMART", "CDD", "ProSitePatterns",
+                         "SUPERFAMILY", "Gene3D"]
+
+    # 1. Submit job
+    payload = {
+        "email": email,
+        "sequence": sequence,
+        "appl": ",".join(applications),
+        "goterms": "true",
+        "pathways": "true",
+    }
+    resp = requests.post(f"{IPRSCAN_API}/run", data=payload)
+    resp.raise_for_status()
+    job_id = resp.text.strip()
+    print(f"InterProScan job submitted: {job_id}")
+
+    # 2. Poll for results
+    max_wait = 600  # 10 min
+    elapsed = 0
+    while elapsed < max_wait:
+        status_resp = requests.get(f"{IPRSCAN_API}/status/{job_id}")
+        status = status_resp.text.strip()
+        if status == "FINISHED":
+            break
+        elif status in ("ERROR", "FAILURE", "NOT_FOUND"):
+            raise RuntimeError(f"InterProScan job {job_id}: {status}")
+        time.sleep(30)
+        elapsed += 30
+        print(f"  Waiting... ({elapsed}s, status={status})")
+
+    # 3. Get results
+    result_resp = requests.get(f"{IPRSCAN_API}/result/{job_id}/json")
+    result_resp.raise_for_status()
+    results = result_resp.json()
+
+    # Parse matches
+    matches = []
+    for res in results.get("results", [results]):
+        for match in res.get("matches", []):
+            sig = match.get("signature", {})
+            for loc in match.get("locations", []):
+                matches.append({
+                    "accession": sig.get("accession", ""),
+                    "name": sig.get("name", ""),
+                    "description": sig.get("description", ""),
+                    "database": sig.get("signatureLibraryRelease", {}).get("library", ""),
+                    "start": loc.get("start", 0),
+                    "end": loc.get("end", 0),
+                    "score": loc.get("score", None),
+                    "evalue": loc.get("evalue", None),
+                    "interpro_accession": (
+                        sig.get("entry", {}).get("accession", "")
+                        if sig.get("entry") else ""
+                    ),
+                    "interpro_name": (
+                        sig.get("entry", {}).get("name", "")
+                        if sig.get("entry") else ""
+                    ),
+                })
+
+    df = pd.DataFrame(matches)
+    print(f"InterProScan: {len(df)} domain matches from {len(applications)} DBs")
+    return df, job_id
+```
+
+## 4. ドメインアーキテクチャ可視化
+
+```python
+import matplotlib
+matplotlib.use("Agg")
+import matplotlib.pyplot as plt
+import matplotlib.patches as mpatches
+
+
+def visualize_domain_architecture(domains_df, protein_length=None,
+                                    output="figures/domain_architecture.png"):
+    """
+    ドメインアーキテクチャ図を生成。
+
+    Parameters:
+        domains_df: DataFrame — columns: [name, start, end, source]
+        protein_length: int — 全長 (None なら max(end) 使用)
+        output: str — 出力ファイルパス
+    """
+    import os
+    os.makedirs(os.path.dirname(output), exist_ok=True)
+
+    if protein_length is None:
+        protein_length = int(domains_df["end"].max()) + 10
+
+    # 色パレット
+    colors = plt.cm.Set3.colors
+    unique_sources = domains_df["source"].unique() if "source" in domains_df.columns else [""]
+    source_color = {s: colors[i % len(colors)] for i, s in enumerate(unique_sources)}
+
+    fig, ax = plt.subplots(figsize=(14, 3))
+
+    # バックボーン
+    ax.plot([0, protein_length], [0.5, 0.5], "k-", linewidth=2)
+
+    # ドメインボックス
+    for _, row in domains_df.iterrows():
+        start = row["start"]
+        end = row["end"]
+        source = row.get("source", "")
+        color = source_color.get(source, "steelblue")
+
+        rect = mpatches.FancyBboxPatch(
+            (start, 0.2), end - start, 0.6,
+            boxstyle="round,pad=0.02",
+            facecolor=color, edgecolor="black", linewidth=1
+        )
+        ax.add_patch(rect)
+
+        # ラベル
+        mid = (start + end) / 2
+        label = row.get("name", row.get("accession", ""))
+        if len(label) > 12:
+            label = label[:10] + ".."
+        ax.text(mid, 0.5, label, ha="center", va="center",
+                fontsize=7, fontweight="bold")
+
+    ax.set_xlim(-10, protein_length + 10)
+    ax.set_ylim(-0.5, 1.5)
+    ax.set_xlabel("Residue position")
+    ax.set_title("Domain Architecture")
+    ax.set_yticks([])
+
+    plt.tight_layout()
+    plt.savefig(output, dpi=150, bbox_inches="tight")
+    plt.close()
+    print(f"Domain architecture: {output}")
+    return output
+```
+
+## 5. ドメインファミリー比較
+
+```python
+def compare_domain_architectures(protein_list):
+    """
+    複数タンパク質のドメインアーキテクチャを比較。
+
+    Parameters:
+        protein_list: list of str — UniProt accessions
+    """
+    all_domains = {}
+    for uniprot_id in protein_list:
+        try:
+            df = get_protein_domains(uniprot_id)
+            all_domains[uniprot_id] = df
+        except Exception as e:
+            print(f"  Warning: {uniprot_id} failed — {e}")
+            all_domains[uniprot_id] = pd.DataFrame()
+
+    # 共通ドメイン分析
+    domain_sets = {}
+    for prot, df in all_domains.items():
+        if not df.empty:
+            domain_sets[prot] = set(df["accession"].unique())
+        else:
+            domain_sets[prot] = set()
+
+    # 全タンパク質に共通するドメイン
+    if domain_sets:
+        common = set.intersection(*domain_sets.values()) if domain_sets else set()
+        all_unique = set.union(*domain_sets.values()) if domain_sets else set()
+    else:
+        common = set()
+        all_unique = set()
+
+    summary = {
+        "proteins_analyzed": len(protein_list),
+        "proteins_with_domains": sum(
+            1 for df in all_domains.values() if not df.empty
+        ),
+        "common_domains": sorted(common),
+        "total_unique_domains": len(all_unique),
+        "per_protein": {
+            prot: {"count": len(s), "domains": sorted(s)}
+            for prot, s in domain_sets.items()
+        },
+    }
+
+    print(f"Domain comparison: {len(protein_list)} proteins, "
+          f"{len(common)} common domains, "
+          f"{len(all_unique)} unique domains total")
+    return summary, all_domains
+```
+
+## References
+
+### Output Files
+
+| ファイル | 形式 |
+|---|---|
+| `results/interpro_search.csv` | CSV |
+| `results/protein_domains.csv` | CSV |
+| `results/interproscan_results.csv` | CSV |
+| `results/domain_comparison.json` | JSON |
+| `figures/domain_architecture.png` | PNG |
+
+### 利用可能ツール
+
+| カテゴリ | 主要ツール | 用途 |
+|---|---|---|
+| InterPro | `InterPro_search_domains` | ドメイン検索 |
+| InterPro | `InterPro_get_protein_domains` | タンパク質ドメイン取得 |
+| InterPro | `InterPro_get_domain_details` | ドメイン詳細 |
+| InterProScan | `InterProScan_scan_sequence` | 配列ベース予測 |
+| InterProScan | `InterProScan_get_job_status` | ジョブステータス |
+| InterProScan | `InterProScan_get_job_results` | 結果取得 |
+
+### 参照スキル
+
+| スキル | 関連 |
+|---|---|
+| `scientific-protein-structure-analysis` | 3D 構造解析 |
+| `scientific-protein-interaction-network` | PPI ネットワーク |
+| `scientific-sequence-alignment` | 多重配列アラインメント |
+| `scientific-phylogenetics` | 系統樹構築 |
+| `scientific-gene-expression-transcriptomics` | 発現相関 |
+
+### 依存パッケージ
+
+`requests`, `pandas`, `matplotlib`, `json` (stdlib), `time` (stdlib)