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export const GTEX_ORGAN_PROFILES: Record<OrganType, OrganProfile> = {
liver: {
id: 'liver',
name: 'Human Liver (Hepatic)',
description: 'GTEx V8 Hepatic Transcriptomics profile dominated by phase I/II xenobiotic metabolism enzymes.',
markerGenes: ['CYP3A4', 'CYP2D6', 'CYP2C9', 'ALB', 'APOB', 'GSTA1', 'SLCO1B1'],
geneExpressionValues: Array.from({ length: 128 }, (_, i) => Math.sin(i * 0.15) * 2.5 + (i % 5 === 0 ? 4.2 : 0.8))
},
heart: {
id: 'heart',
name: 'Human Heart (Left Ventricle)',
description: 'GTEx V8 Cardiac Ventricular profile enriched in hERG channels, ion channels, and contractile sarcomeres.',
markerGenes: ['MYH6', 'TNNT2', 'MYL2', 'KCNH2', 'SCN5A', 'ACTC1', 'PLN'],
geneExpressionValues: Array.from({ length: 128 }, (_, i) => Math.cos(i * 0.12) * 2.8 + (i % 4 === 0 ? 3.9 : 0.5))
},
kidney: {
id: 'kidney',
name: 'Human Kidney (Renal Cortex)',
description: 'GTEx V8 Renal Cortex profile enriched in organic anion/cation transporters (OAT/OCT) and filtration barrier markers.',
markerGenes: ['SLC22A2', 'UMOD', 'CUBN', 'LRP2', 'SLC22A6', 'NPHS1', 'REN'],
geneExpressionValues: Array.from({ length: 128 }, (_, i) => Math.sin(i * 0.18 + 1.0) * 2.2 + (i % 3 === 0 ? 3.6 : 0.9))
},
brain: {
id: 'brain',
name: 'Human Brain (Cortex & Hippocampus)',
description: 'GTEx V8 CNS Cortex profile enriched in neurotransmitter receptors, ionotropic channels, and glial markers.',
markerGenes: ['GFAP', 'SYP', 'MBP', 'GRIN1', 'GABRA1', 'DRD2', 'HTR2A'],
geneExpressionValues: Array.from({ length: 128 }, (_, i) => Math.cos(i * 0.14 + 0.5) * 2.4 + (i % 6 === 0 ? 4.5 : 0.6))
},
lung: {
id: 'lung',
name: 'Human Lung (Alveolar Tissue)',
description: 'GTEx V8 Pulmonary Alveolar profile rich in surfactant proteins and capillary endothelial receptors.',
markerGenes: ['SFTPB', 'CLDN18', 'SFTPA1', 'AGER', 'LAMP3', 'ACE2', 'CAV1'],
geneExpressionValues: Array.from({ length: 128 }, (_, i) => Math.sin(i * 0.2 + 2.0) * 2.1 + (i % 7 === 0 ? 3.8 : 0.7))
}
};
export const SIDER_BENCHMARK_DRUGS: DrugRecord[] = [
{
id: 'acetaminophen',
name: 'Acetaminophen (Paracetamol)',
smiles: 'CC(=O)NC1=CC=C(O)C=C1',
cid: 1983,
fdaApproved: true,
indication: 'Analgesic & Antipyretic',
adrLabels: {
hepatotoxicity: 1,
cardiotoxicity: 0,
nephrotoxicity: 1,
neurotoxicity: 0,
pulmotoxicity: 0,
gastrointestinal: 0,
dermatological: 1,
hematological: 0,
metabolic: 0,
systemic_fatigue: 0
},
organScores: {
liver: 0.92, // High NAPQI metabolite hepatotoxicity
heart: 0.12,
kidney: 0.54,
brain: 0.15,
lung: 0.10
},
tanimotoBaseline: 0.88
},
{
id: 'doxorubicin',
name: 'Doxorubicin',
smiles: 'CC1C(C(CC(O1)OC2CC(CC3=C(C4=C(C(=C23)O)C(=O)C5=C(C4=O)C=CC=C5OC)O)(C(=O)CO)O)N)O',
cid: 31703,
fdaApproved: true,
indication: 'Chemotherapeutic Anthracycline',
adrLabels: {
hepatotoxicity: 1,
cardiotoxicity: 1,
nephrotoxicity: 1,
neurotoxicity: 0,
pulmotoxicity: 0,
gastrointestinal: 1,
dermatological: 1,
hematological: 1,
metabolic: 1,
systemic_fatigue: 1
},
organScores: {
liver: 0.65,
heart: 0.96, // Severe irreversible dilated cardiomyopathy
kidney: 0.58,
brain: 0.22,
lung: 0.35
},
tanimotoBaseline: 0.82
},
{
id: 'amiodarone',
name: 'Amiodarone',
smiles: 'CCCCCC1=C(C2=CC=CC=C2O1)C(=O)C3=CC(=C(C(=C3)I)OCCN(CC)CC)I',
cid: 2157,
fdaApproved: true,
indication: 'Class III Antiarrhythmic',
adrLabels: {
hepatotoxicity: 1,
cardiotoxicity: 1,
nephrotoxicity: 0,
neurotoxicity: 1,
pulmotoxicity: 1,
gastrointestinal: 0,
dermatological: 1,
hematological: 0,
metabolic: 1,
systemic_fatigue: 1
},
organScores: {
liver: 0.78,
heart: 0.62,
kidney: 0.25,
brain: 0.52,
lung: 0.94 // Pulmonary fibrosis & interstitial pneumonitis
},
tanimotoBaseline: 0.79
},
{
id: 'cisplatin',
name: 'Cisplatin',
smiles: 'N.N.Cl[Pt]Cl',
cid: 84691,
fdaApproved: true,
indication: 'Platinum Antineoplastic',
adrLabels: {
hepatotoxicity: 0,
cardiotoxicity: 0,
nephrotoxicity: 1,
neurotoxicity: 1,
pulmotoxicity: 0,
gastrointestinal: 1,
dermatological: 0,
hematological: 1,
metabolic: 1,
systemic_fatigue: 1
},
organScores: {
liver: 0.38,
heart: 0.28,
kidney: 0.95, // Severe acute kidney injury (AKI)
brain: 0.72, // Ototoxicity & peripheral neuropathy
lung: 0.18
},
tanimotoBaseline: 0.85
},
{
id: 'haloperidol',
name: 'Haloperidol',
smiles: 'O=C(CCCN1CCC(O)(c2ccc(Cl)cc2)CC1)c3ccc(F)cc3',
cid: 3559,
fdaApproved: true,
indication: 'First-Generation Antipsychotic',
adrLabels: {
hepatotoxicity: 0,
cardiotoxicity: 1,
nephrotoxicity: 0,
neurotoxicity: 1,
pulmotoxicity: 0,
gastrointestinal: 0,
dermatological: 0,
hematological: 0,
metabolic: 1,
systemic_fatigue: 1
},
organScores: {
liver: 0.22,
heart: 0.81, // hERG channel blockade & QT prolongation
kidney: 0.18,
brain: 0.91, // Extrapyramidal symptoms & tardive dyskinesia
lung: 0.12
},
tanimotoBaseline: 0.76
},
{
id: 'aspirin',
name: 'Aspirin (Acetylsalicylic Acid)',
smiles: 'CC(=O)OC1=CC=CC=C1C(=O)O',
cid: 2244,
fdaApproved: true,
indication: 'NSAID & Antiplatelet',
adrLabels: {
hepatotoxicity: 0,
cardiotoxicity: 0,
nephrotoxicity: 1,
neurotoxicity: 0,
pulmotoxicity: 0,
gastrointestinal: 1,
dermatological: 1,
hematological: 1,
metabolic: 0,
systemic_fatigue: 0
},
organScores: {
liver: 0.28,
heart: 0.15,
kidney: 0.45,
brain: 0.18,
lung: 0.22
},
tanimotoBaseline: 0.91
},
{
id: 'metformin',
name: 'Metformin',
smiles: 'CN(C)C(=N)NC(=N)N',
cid: 4091,
fdaApproved: true,
indication: 'Antidiabetic Biguanide',
adrLabels: {
hepatotoxicity: 0,
cardiotoxicity: 0,
nephrotoxicity: 0,
neurotoxicity: 0,
pulmotoxicity: 0,
gastrointestinal: 1,
dermatological: 0,
hematological: 0,
metabolic: 1,
systemic_fatigue: 0
},
organScores: {
liver: 0.15,
heart: 0.10,
kidney: 0.38,
brain: 0.08,
lung: 0.05
},
tanimotoBaseline: 0.89
},
{
id: 'sorafenib',
name: 'Sorafenib',
smiles: 'CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F',
cid: 216239,
fdaApproved: true,
indication: 'Multi-Kinase Inhibitor',
adrLabels: {
hepatotoxicity: 1,
cardiotoxicity: 1,
nephrotoxicity: 0,
neurotoxicity: 0,
pulmotoxicity: 0,
gastrointestinal: 1,
dermatological: 1,
hematological: 1,
metabolic: 1,
systemic_fatigue: 1
},
organScores: {
liver: 0.72,
heart: 0.68,
kidney: 0.32,
brain: 0.20,
lung: 0.28
},
tanimotoBaseline: 0.74
}
];
/**
* Generate a 128-dim Morgan-like binary/count fingerprint from SMILES string
*/
export function generateMorganFingerprint(smiles: string, numBits: number = 128): number[] {
const fp = new Array(numBits).fill(0);
if (!smiles) return fp;
let seed = 0;
for (let i = 0; i < smiles.length; i++) {
const charCode = smiles.charCodeAt(i);
seed = (seed << 5) - seed + charCode;
seed |= 0;
}
for (let i = 0; i < smiles.length; i++) {
const charCode = smiles.charCodeAt(i);
const bitIndex1 = Math.abs((seed + charCode * 31 + i * 17) % numBits);
const bitIndex2 = Math.abs((seed ^ (charCode * 13) + i * 7) % numBits);
fp[bitIndex1] = 1;
fp[bitIndex2] = 1;
}
// Add functional group flags based on substring patterns
if (smiles.includes('C1=CC=CC=C1') || smiles.includes('c1ccccc1')) {
// Aromatic Benzene
fp[12] = 1; fp[28] = 1; fp[45] = 1;
}
if (smiles.includes('(=O)') || smiles.includes('=O')) {
// Carbonyl
fp[5] = 1; fp[33] = 1;
}
if (smiles.includes('O')) {
// Hydroxyl / Ether
fp[9] = 1; fp[62] = 1;
}
if (smiles.includes('N')) {
// Amine / Amide
fp[14] = 1; fp[81] = 1;
}
if (smiles.includes('Cl') || smiles.includes('F') || smiles.includes('I') || smiles.includes('Br')) {
// Halogen
fp[21] = 1; fp[99] = 1;
}
if (smiles.includes('S') || smiles.includes('P') || smiles.includes('Pt')) {
// Reactive Heteroatom
fp[42] = 1; fp[110] = 1;
}
return fp;
}
/**
* Calculate Tanimoto Similarity between two binary fingerprints (0.0 - 1.0)
*/
export function calculateTanimotoSimilarity(fpA: number[], fpB: number[]): number {
if (fpA.length !== fpB.length) return 0.5;
let intersection = 0;
let union = 0;
for (let i = 0; i < fpA.length; i++) {
const a = fpA[i] > 0 ? 1 : 0;
const b = fpB[i] > 0 ? 1 : 0;
if (a === 1 && b === 1) intersection++;
if (a === 1 || b === 1) union++;
}
return union === 0 ? 0 : intersection / union;
}
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