BigQuery গ্রাফের সাহায্যে ওষুধের পারস্পরিক ক্রিয়া বিশ্লেষণ করুন

(Compound)-[BINDS_TO {affinity_nm, ic50_nm, interaction_type}]->(Target)
(Target)-[PARTICIPATES_IN {role, importance_score}]->(Pathway)

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gcloud config get project

export PROJECT_ID=<YOUR_PROJECT_ID>
gcloud config set project $PROJECT_ID

gcloud services enable bigquery.googleapis.com

CREATE SCHEMA IF NOT EXISTS drug_target_graph
OPTIONS (location = 'US');

CREATE OR REPLACE TABLE drug_target_graph.compounds AS
SELECT 'CPD001' AS compound_id, 'Imatinib'    AS compound_name, 'Kinase Inhibitor'       AS mechanism_of_action, 'Approved'    AS dev_stage, 'Oncology'           AS therapeutic_area, 479.6 AS molecular_weight UNION ALL
SELECT 'CPD002', 'Gefitinib',   'Kinase Inhibitor',        'Approved',    'Oncology',           446.9 UNION ALL
SELECT 'CPD003', 'Erlotinib',   'Kinase Inhibitor',        'Approved',    'Oncology',           393.4 UNION ALL
SELECT 'CPD004', 'Sorafenib',   'Multi-Kinase Inhibitor',  'Approved',    'Oncology',           464.8 UNION ALL
SELECT 'CPD005', 'Vemurafenib', 'BRAF Inhibitor',          'Approved',    'Oncology',           489.9 UNION ALL
SELECT 'CPD006', 'Crizotinib',  'ALK Inhibitor',           'Approved',    'Oncology',           450.3 UNION ALL
SELECT 'CPD007', 'Idelalisib',  'PI3K Inhibitor',          'Approved',    'Oncology',           415.4 UNION ALL
SELECT 'CPD008', 'Trametinib',  'MEK Inhibitor',           'Approved',    'Oncology',           615.4 UNION ALL
SELECT 'CPD009', 'Palbociclib', 'CDK Inhibitor',           'Approved',    'Oncology',           447.5 UNION ALL
SELECT 'CPD010', 'Compound-X1', 'Kinase Inhibitor',        'Phase II',    'Oncology',           412.3 UNION ALL
SELECT 'CPD011', 'Compound-X2', 'PI3K Inhibitor',          'Phase I',     'Oncology',           398.7 UNION ALL
SELECT 'CPD012', 'Saquinavir',  'Protease Inhibitor',      'Approved',    'Infectious Disease', 670.8 UNION ALL
SELECT 'CPD013', 'Metformin',   'AMPK Activator',          'Approved',    'Metabolic',          165.6 UNION ALL
SELECT 'CPD014', 'Rapamycin',   'mTOR Inhibitor',          'Approved',    'Immunology',         914.2 UNION ALL
SELECT 'CPD015', 'Compound-X3', 'Multi-Kinase Inhibitor',  'Preclinical', 'Oncology',           502.1;

CREATE OR REPLACE TABLE drug_target_graph.targets AS
SELECT 'TGT001' AS target_id, 'BCR-ABL1'    AS target_name, 'ABL1'    AS gene_name, 'P00519' AS uniprot_id, 'Kinase'       AS target_class, TRUE  AS is_oncogene UNION ALL
SELECT 'TGT002', 'EGFR',      'EGFR',    'P00533', 'Kinase',       TRUE  UNION ALL
SELECT 'TGT003', 'VEGFR2',    'KDR',     'P35968', 'Kinase',       FALSE UNION ALL
SELECT 'TGT004', 'BRAF',      'BRAF',    'P15056', 'Kinase',       TRUE  UNION ALL
SELECT 'TGT005', 'ALK',       'ALK',     'Q9UM73', 'Kinase',       TRUE  UNION ALL
SELECT 'TGT006', 'PI3K-alpha','PIK3CA',  'P42336', 'Lipid Kinase', TRUE  UNION ALL
SELECT 'TGT007', 'MEK1',      'MAP2K1',  'Q02750', 'Kinase',       FALSE UNION ALL
SELECT 'TGT008', 'CDK4',      'CDK4',    'P11802', 'Kinase',       FALSE UNION ALL
SELECT 'TGT009', 'CDK6',      'CDK6',    'P30279', 'Kinase',       FALSE UNION ALL
SELECT 'TGT010', 'mTOR',      'MTOR',    'P42345', 'Kinase',       FALSE UNION ALL
SELECT 'TGT011', 'PDGFR-beta','PDGFRB',  'P09619', 'Kinase',       FALSE UNION ALL
SELECT 'TGT012', 'c-KIT',     'KIT',     'P10721', 'Kinase',       TRUE  UNION ALL
SELECT 'TGT013', 'hERG',      'KCNH2',   'Q12809', 'Ion Channel',  FALSE UNION ALL
SELECT 'TGT014', 'AMPK',      'PRKAA1',  'Q13131', 'Kinase',       FALSE UNION ALL
SELECT 'TGT015', 'RAF1',      'RAF1',    'P04049', 'Kinase',       FALSE UNION ALL
SELECT 'TGT016', 'RET',       'RET',     'P07949', 'Kinase',       TRUE  UNION ALL
SELECT 'TGT017', 'FLT3',      'FLT3',    'P36888', 'Kinase',       TRUE  UNION ALL
SELECT 'TGT018', 'AKT1',      'AKT1',    'P31749', 'Kinase',       FALSE UNION ALL
SELECT 'TGT019', 'ERK2',      'MAPK1',   'P28482', 'Kinase',       FALSE UNION ALL
SELECT 'TGT020', 'HIV-Protease','HIV1-PR','Q72547', 'Protease',     FALSE;

CREATE OR REPLACE TABLE drug_target_graph.interactions AS
SELECT 'INT001' AS interaction_id, 'CPD001' AS compound_id, 'TGT001' AS target_id, 0.025  AS affinity_nm, 0.038  AS ic50_nm, 'primary'    AS interaction_type, 9.8  AS pchembl_value UNION ALL
SELECT 'INT002', 'CPD001', 'TGT011', 0.1,    0.15,   'primary',    8.8  UNION ALL
SELECT 'INT003', 'CPD001', 'TGT012', 0.068,  0.1,    'primary',    9.2  UNION ALL
SELECT 'INT004', 'CPD001', 'TGT016', 0.5,    0.8,    'off-target', 7.4  UNION ALL
SELECT 'INT005', 'CPD001', 'TGT013', 5.2,    8.1,    'off-target', 6.1  UNION ALL
SELECT 'INT006', 'CPD002', 'TGT002', 0.02,   0.033,  'primary',    9.7  UNION ALL
SELECT 'INT007', 'CPD002', 'TGT013', 3.1,    4.8,    'off-target', 6.5  UNION ALL
SELECT 'INT008', 'CPD003', 'TGT002', 0.058,  0.079,  'primary',    9.2  UNION ALL
SELECT 'INT009', 'CPD003', 'TGT013', 8.5,    12.0,   'off-target', 5.9  UNION ALL
SELECT 'INT010', 'CPD004', 'TGT003', 0.09,   0.12,   'primary',    9.1  UNION ALL
SELECT 'INT011', 'CPD004', 'TGT004', 0.038,  0.055,  'primary',    8.9  UNION ALL
SELECT 'INT012', 'CPD004', 'TGT015', 0.22,   0.31,   'primary',    8.5  UNION ALL
SELECT 'INT013', 'CPD004', 'TGT016', 0.58,   0.75,   'primary',    8.1  UNION ALL
SELECT 'INT014', 'CPD004', 'TGT017', 0.33,   0.48,   'primary',    8.4  UNION ALL
SELECT 'INT015', 'CPD004', 'TGT013', 2.8,    4.1,    'off-target', 6.6  UNION ALL
SELECT 'INT016', 'CPD005', 'TGT004', 0.031,  0.044,  'primary',    9.5  UNION ALL
SELECT 'INT017', 'CPD005', 'TGT015', 0.48,   0.65,   'off-target', 7.3  UNION ALL
SELECT 'INT018', 'CPD006', 'TGT005', 0.02,   0.028,  'primary',    9.8  UNION ALL
SELECT 'INT019', 'CPD006', 'TGT003', 0.41,   0.59,   'off-target', 7.4  UNION ALL
SELECT 'INT020', 'CPD007', 'TGT006', 0.019,  0.025,  'primary',    9.8  UNION ALL
SELECT 'INT021', 'CPD007', 'TGT018', 0.55,   0.78,   'off-target', 7.2  UNION ALL
SELECT 'INT022', 'CPD008', 'TGT007', 0.0092, 0.014,  'primary',    10.1 UNION ALL
SELECT 'INT023', 'CPD008', 'TGT019', 0.38,   0.51,   'off-target', 7.4  UNION ALL
SELECT 'INT024', 'CPD009', 'TGT008', 0.011,  0.017,  'primary',    9.9  UNION ALL
SELECT 'INT025', 'CPD009', 'TGT009', 0.015,  0.022,  'primary',    9.8  UNION ALL
SELECT 'INT026', 'CPD010', 'TGT002', 0.041,  0.058,  'primary',    9.4  UNION ALL
SELECT 'INT027', 'CPD010', 'TGT001', 0.38,   0.52,   'off-target', 7.3  UNION ALL
SELECT 'INT028', 'CPD010', 'TGT013', 1.2,    1.8,    'off-target', 7.1  UNION ALL
SELECT 'INT029', 'CPD011', 'TGT006', 0.029,  0.041,  'primary',    9.5  UNION ALL
SELECT 'INT030', 'CPD011', 'TGT010', 0.71,   0.95,   'off-target', 7.0  UNION ALL
SELECT 'INT031', 'CPD012', 'TGT020', 0.39,   0.55,   'primary',    7.3  UNION ALL
SELECT 'INT032', 'CPD013', 'TGT014', 12.0,   18.5,   'primary',    5.7  UNION ALL
SELECT 'INT033', 'CPD014', 'TGT010', 0.0018, 0.0025, 'primary',    11.8 UNION ALL
SELECT 'INT034', 'CPD015', 'TGT004', 0.055,  0.078,  'primary',    9.2  UNION ALL
SELECT 'INT035', 'CPD015', 'TGT003', 0.12,   0.17,   'primary',    8.9  UNION ALL
SELECT 'INT036', 'CPD015', 'TGT016', 0.29,   0.41,   'primary',    8.5  UNION ALL
SELECT 'INT037', 'CPD015', 'TGT013', 0.95,   1.35,   'off-target', 7.2;

CREATE OR REPLACE TABLE drug_target_graph.pathways AS
SELECT 'PWY001' AS pathway_id, 'MAPK Signaling'           AS pathway_name, 'hsa04010' AS kegg_id, 'Cell Proliferation'     AS biological_process, 'Oncology'           AS disease_area, 'high'   AS cancer_relevance UNION ALL
SELECT 'PWY002', 'PI3K-AKT Signaling',        'hsa04151', 'Cell Survival',         'Oncology',           'high'   UNION ALL
SELECT 'PWY003', 'VEGF Signaling',             'hsa04370', 'Angiogenesis',          'Oncology',           'high'   UNION ALL
SELECT 'PWY004', 'ErbB Signaling',             'hsa04012', 'Cell Growth',           'Oncology',           'high'   UNION ALL
SELECT 'PWY005', 'mTOR Signaling',             'hsa04150', 'Cell Growth',           'Oncology',           'medium' UNION ALL
SELECT 'PWY006', 'Cell Cycle',                 'hsa04110', 'Cell Division',         'Oncology',           'high'   UNION ALL
SELECT 'PWY007', 'Cardiac Muscle Contraction', 'hsa04260', 'Cardiac Function',      'Cardiovascular',     'low'    UNION ALL
SELECT 'PWY008', 'hERG Cardiac Channel',       'hsa04022', 'Cardiac Repolarisation','Cardiovascular',     'low'    UNION ALL
SELECT 'PWY009', 'AMPK Signaling',             'hsa04152', 'Energy Metabolism',     'Metabolic',          'low'    UNION ALL
SELECT 'PWY010', 'ALK Signaling',              'hsa04915', 'Cell Proliferation',    'Oncology',           'high'   UNION ALL
SELECT 'PWY011', 'RAS Signaling',              'hsa04014', 'Cell Proliferation',    'Oncology',           'high'   UNION ALL
SELECT 'PWY012', 'HIV Replication',            'hsa05170', 'Viral Replication',     'Infectious Disease', 'low';

CREATE OR REPLACE TABLE drug_target_graph.target_pathways AS
SELECT 'TP001' AS tp_id, 'TGT001' AS target_id, 'PWY001' AS pathway_id, 'activator' AS role, 0.95 AS importance_score UNION ALL
SELECT 'TP002', 'TGT001', 'PWY011', 'activator', 0.88 UNION ALL
SELECT 'TP003', 'TGT002', 'PWY004', 'activator', 0.98 UNION ALL
SELECT 'TP004', 'TGT002', 'PWY001', 'activator', 0.82 UNION ALL
SELECT 'TP005', 'TGT002', 'PWY002', 'activator', 0.75 UNION ALL
SELECT 'TP006', 'TGT003', 'PWY003', 'activator', 0.96 UNION ALL
SELECT 'TP007', 'TGT003', 'PWY001', 'activator', 0.71 UNION ALL
SELECT 'TP008', 'TGT004', 'PWY001', 'activator', 0.97 UNION ALL
SELECT 'TP009', 'TGT004', 'PWY011', 'activator', 0.89 UNION ALL
SELECT 'TP010', 'TGT005', 'PWY010', 'activator', 0.99 UNION ALL
SELECT 'TP011', 'TGT005', 'PWY001', 'activator', 0.78 UNION ALL
SELECT 'TP012', 'TGT006', 'PWY002', 'activator', 0.98 UNION ALL
SELECT 'TP013', 'TGT006', 'PWY005', 'activator', 0.85 UNION ALL
SELECT 'TP014', 'TGT007', 'PWY001', 'activator', 0.94 UNION ALL
SELECT 'TP015', 'TGT007', 'PWY011', 'activator', 0.88 UNION ALL
SELECT 'TP016', 'TGT008', 'PWY006', 'activator', 0.95 UNION ALL
SELECT 'TP017', 'TGT009', 'PWY006', 'activator', 0.93 UNION ALL
SELECT 'TP018', 'TGT010', 'PWY005', 'activator', 0.99 UNION ALL
SELECT 'TP019', 'TGT010', 'PWY002', 'activator', 0.91 UNION ALL
SELECT 'TP020', 'TGT011', 'PWY003', 'activator', 0.87 UNION ALL
SELECT 'TP021', 'TGT011', 'PWY001', 'activator', 0.72 UNION ALL
SELECT 'TP022', 'TGT012', 'PWY001', 'activator', 0.83 UNION ALL
SELECT 'TP023', 'TGT012', 'PWY011', 'activator', 0.79 UNION ALL
SELECT 'TP024', 'TGT013', 'PWY008', 'substrate', 0.99 UNION ALL
SELECT 'TP025', 'TGT013', 'PWY007', 'substrate', 0.95 UNION ALL
SELECT 'TP026', 'TGT014', 'PWY009', 'activator', 0.97 UNION ALL
SELECT 'TP027', 'TGT015', 'PWY001', 'activator', 0.91 UNION ALL
SELECT 'TP028', 'TGT015', 'PWY011', 'activator', 0.86 UNION ALL
SELECT 'TP029', 'TGT016', 'PWY001', 'activator', 0.84 UNION ALL
SELECT 'TP030', 'TGT016', 'PWY003', 'activator', 0.77 UNION ALL
SELECT 'TP031', 'TGT017', 'PWY001', 'activator', 0.88 UNION ALL
SELECT 'TP032', 'TGT017', 'PWY011', 'activator', 0.82 UNION ALL
SELECT 'TP033', 'TGT018', 'PWY002', 'activator', 0.96 UNION ALL
SELECT 'TP034', 'TGT018', 'PWY005', 'activator', 0.88 UNION ALL
SELECT 'TP035', 'TGT019', 'PWY001', 'activator', 0.97 UNION ALL
SELECT 'TP036', 'TGT019', 'PWY011', 'activator', 0.91 UNION ALL
SELECT 'TP037', 'TGT020', 'PWY012', 'substrate', 0.99;

CREATE OR REPLACE PROPERTY GRAPH drug_target_graph.drug_target_interaction_graph
NODE TABLES (
  drug_target_graph.compounds
    AS compound_node
    KEY (compound_id)
    LABEL Compound
    PROPERTIES (compound_id, compound_name, mechanism_of_action, dev_stage, therapeutic_area, molecular_weight),

  drug_target_graph.targets
    AS target_node
    KEY (target_id)
    LABEL Target
    PROPERTIES (target_id, target_name, gene_name, uniprot_id, target_class, is_oncogene),

  drug_target_graph.pathways
    AS pathway_node
    KEY (pathway_id)
    LABEL Pathway
    PROPERTIES (pathway_id, pathway_name, kegg_id, biological_process, disease_area, cancer_relevance)
)
EDGE TABLES (
  drug_target_graph.interactions
    AS binds_to_edge
    KEY (interaction_id)
    SOURCE KEY (compound_id) REFERENCES compound_node (compound_id)
    DESTINATION KEY (target_id) REFERENCES target_node (target_id)
    LABEL BINDS_TO
    PROPERTIES (interaction_id, affinity_nm, ic50_nm, interaction_type, pchembl_value),

  drug_target_graph.target_pathways
    AS participates_in_edge
    KEY (tp_id)
    SOURCE KEY (target_id) REFERENCES target_node (target_id)
    DESTINATION KEY (pathway_id) REFERENCES pathway_node (pathway_id)
    LABEL PARTICIPATES_IN
    PROPERTIES (tp_id, role, importance_score)
);

SELECT
  compound_name,
  dev_stage,
  target_name,
  gene_name,
  target_class,
  interaction_type,
  ROUND(affinity_nm, 3) AS affinity_nm,
  ROUND(ic50_nm, 3)     AS ic50_nm,
  pchembl_value
FROM GRAPH_TABLE(
  drug_target_graph.drug_target_interaction_graph
  MATCH (c:Compound)-[b:BINDS_TO]->(t:Target)
  COLUMNS (
    c.compound_name    AS compound_name,
    c.dev_stage        AS dev_stage,
    t.target_name      AS target_name,
    t.gene_name        AS gene_name,
    t.target_class     AS target_class,
    b.interaction_type AS interaction_type,
    b.affinity_nm      AS affinity_nm,
    b.ic50_nm          AS ic50_nm,
    b.pchembl_value    AS pchembl_value
  )
)
ORDER BY compound_name, interaction_type, affinity_nm;

SELECT
  compound_name,
  dev_stage,
  therapeutic_area,
  target_name,
  ROUND(affinity_nm, 3) AS herg_affinity_nm,
  pathway_name,
  disease_area          AS pathway_disease_area
FROM GRAPH_TABLE(
  drug_target_graph.drug_target_interaction_graph
  MATCH (c:Compound)-[b:BINDS_TO]->(t:Target)-[p:PARTICIPATES_IN]->(pw:Pathway)
  WHERE t.gene_name        = 'KCNH2'
    AND b.interaction_type = 'off-target'
    AND pw.disease_area    = 'Cardiovascular'
  COLUMNS (
    c.compound_name    AS compound_name,
    c.dev_stage        AS dev_stage,
    c.therapeutic_area AS therapeutic_area,
    t.target_name      AS target_name,
    b.affinity_nm      AS affinity_nm,
    pw.pathway_name    AS pathway_name,
    pw.disease_area    AS disease_area
  )
)
ORDER BY herg_affinity_nm;

GRAPH `drug_target_graph.drug_target_interaction_graph`
MATCH pt = (c:Compound)-[b:BINDS_TO]->(t:Target)-[p:PARTICIPATES_IN]->(pw:Pathway)
WHERE t.gene_name     = 'KCNH2'
  AND pw.disease_area = 'Cardiovascular'
RETURN
  TO_JSON(pt) AS path

SELECT
  c.compound_name,
  c.dev_stage,
  c.therapeutic_area,
  t.target_name,
  ROUND(i.affinity_nm, 3) AS herg_affinity_nm,
  pw.pathway_name,
  pw.disease_area         AS pathway_disease_area
FROM drug_target_graph.compounds c
JOIN drug_target_graph.interactions i ON c.compound_id = i.compound_id
JOIN drug_target_graph.targets t ON i.target_id = t.target_id
JOIN drug_target_graph.target_pathways tp ON t.target_id = tp.target_id
JOIN drug_target_graph.pathways pw ON tp.pathway_id = pw.pathway_id
WHERE t.gene_name = 'KCNH2'
  AND i.interaction_type = 'off-target'
  AND pw.disease_area = 'Cardiovascular'
ORDER BY herg_affinity_nm;

(Compound)-[METABOLISES_INTO]->(Metabolite)-[BINDS_TO]->
(Target)-[PARTICIPATES_IN]->(Pathway)

SELECT
  compound_a,
  compound_b,
  shared_target,
  gene_name,
  ROUND(affinity_a_nm, 3) AS affinity_a_nm,
  ROUND(affinity_b_nm, 3) AS affinity_b_nm
FROM GRAPH_TABLE(
  drug_target_graph.drug_target_interaction_graph
  MATCH (c1:Compound)-[b1:BINDS_TO]->(t:Target)<-[b2:BINDS_TO]-(c2:Compound)
  WHERE c1.compound_id < c2.compound_id
    AND c1.therapeutic_area = 'Oncology'
    AND c2.therapeutic_area = 'Oncology'
  COLUMNS (
    c1.compound_name AS compound_a,
    c2.compound_name AS compound_b,
    t.target_name    AS shared_target,
    t.gene_name      AS gene_name,
    b1.affinity_nm   AS affinity_a_nm,
    b2.affinity_nm   AS affinity_b_nm
  )
)
ORDER BY compound_a, compound_b, affinity_a_nm;

GRAPH `drug_target_graph.drug_target_interaction_graph`
MATCH p = (c1:Compound)-[b1:BINDS_TO]->(t:Target)<-[b2:BINDS_TO]-(c2:Compound)
WHERE c1.compound_id < c2.compound_id
  AND c1.therapeutic_area = 'Oncology'
RETURN
  TO_JSON(p) AS path

SELECT
  compound_name,
  dev_stage,
  disease_area,
  COUNT(DISTINCT pathway_id) AS pathways_affected,
  COUNT(DISTINCT target_id)  AS targets_involved,
  STRING_AGG(DISTINCT pathway_name ORDER BY pathway_name) AS pathway_list
FROM GRAPH_TABLE(
  drug_target_graph.drug_target_interaction_graph
  MATCH (c:Compound)-[b:BINDS_TO]->(t:Target)-[p:PARTICIPATES_IN]->(pw:Pathway)
  COLUMNS (
    c.compound_name AS compound_name,
    c.dev_stage     AS dev_stage,
    t.target_id     AS target_id,
    pw.pathway_id   AS pathway_id,
    pw.pathway_name AS pathway_name,
    pw.disease_area AS disease_area
  )
)
GROUP BY compound_name, dev_stage, disease_area
ORDER BY compound_name, pathways_affected DESC;

WITH oncology_compounds AS (
  SELECT DISTINCT compound_id, compound_name, dev_stage
  FROM GRAPH_TABLE(
    drug_target_graph.drug_target_interaction_graph
    MATCH (c:Compound)-[b:BINDS_TO]->(t:Target)-[p:PARTICIPATES_IN]->(pw:Pathway)
    WHERE pw.disease_area     = 'Oncology'
      AND pw.cancer_relevance = 'high'
    COLUMNS (
      c.compound_id   AS compound_id,
      c.compound_name AS compound_name,
      c.dev_stage     AS dev_stage
    )
  )
),
herg_risk_compounds AS (
  SELECT DISTINCT compound_id
  FROM GRAPH_TABLE(
    drug_target_graph.drug_target_interaction_graph
    MATCH (c:Compound)-[b:BINDS_TO]->(t:Target)
    WHERE t.gene_name = 'KCNH2'
    COLUMNS (c.compound_id AS compound_id)
  )
)
SELECT
  o.compound_name,
  o.dev_stage,
  'Clean cardiac profile' AS cardiac_safety
FROM oncology_compounds o
LEFT JOIN herg_risk_compounds h ON o.compound_id = h.compound_id
WHERE h.compound_id IS NULL
ORDER BY o.dev_stage, o.compound_name;

DROP SCHEMA IF EXISTS drug_target_graph CASCADE;