Eight-Organ Transporter
Validation Report
Transporter screening across eight organ barriers
Spirographic AI predicts drug behavior across 8 organ barrier systems (57 transporter-organ pairs), a dual cardiac safety panel.
This report documents validation accuracy for every component against curated ground truth with full confusion matrices.
Per-organ summary
| Organ | Correct/Total | Accuracy | Transporters |
|---|---|---|---|
| Placental | 298/315 | 94.6% | 7 (PGP, MRP1, MRP2, MRP5, ENT, LAT1, OATP2B1) |
| Milk | 498/529 | 94.1% | 10 (BCRP, CNT1, CNT3, ENT1, MATE1, MRP1, MRP2, OCT1, OCT2, PGP) |
| Pulmonary | 189/203 | 93.1% | 4 (BCRP, MRP1, MRP5, PGP) |
| Retinal | 241/260 | 92.7% | 5 (BCRP, MRP1, MRP4, MRP5, PGP) |
| Gut | 409/454 | 90.1% | 10 (BCRP, CNT2, MCT1, MCT4, MRP2, OATP1A2, OATP2B1, OCT1, PEPT1, PGP) |
| Renal | 211/235 | 89.8% | 7 (MATE1, MATE2K, MRP2, MRP4, OAT1, OAT3, OCT2) |
| BBB | 259/292 | 88.7% | 7 (GLUT1, LAT1, MCT1, MRP2, MRP4, OATP2B1, PGP) |
| Hepatic | 284/325 | 87.4% | 9 (BCRP, BSEP, MRP2, MRP4, OATP1B1, OATP1B3, OATP2B1, OCT1, PGP) |
Transporter-level confusion matrices
Expand each organ to review transporter-level counts, sensitivity, specificity, accuracy, and the reported misclassifications.
2. Blood-Brain Barrier (BBB)88.7% accuracy
Validated transporters across endothelial tight junctions of cerebral capillaries. Efflux transporters (PGP, MRP2, MRP4) pump drugs back to blood. Influx transporters (LAT1, MCT1, OATP2B1, GLUT1) facilitate nutrient and drug entry into the brain.
| Transporter | N | TP | TN | FP | FN | Sens | Spec | Acc |
|---|---|---|---|---|---|---|---|---|
| GLUT1* | 23 | 13 | 9 | 1 | 0 | 100.0% | 90.0% | 95.7% |
| LAT1* | 23 | 7 | 13 | 0 | 3 | 70.0% | 100.0% | 87.0% |
| MCT1 | 29 | 16 | 12 | 0 | 1 | 94.1% | 100.0% | 96.6% |
| MRP2 | 45 | 28 | 13 | 0 | 4 | 87.5% | 100.0% | 91.1% |
| MRP4 | 59 | 15 | 32 | 1 | 11 | 57.7% | 97.0% | 79.7% |
| OATP2B1 | 35 | 18 | 15 | 0 | 2 | 90.0% | 100.0% | 94.3% |
| PGP | 78 | 40 | 28 | 0 | 10 | 80.0% | 100.0% | 87.2% |
| TOTAL | 292 | 137 | 122 | 2 | 31 | 81.5% | 98.4% | 88.7% |
* Sample size is too small (N < 25); interpret these transporter-specific results cautiously.
Misclassified drugs
Misclassified drugs: GLUT1 FP: L_glucose. LAT1 FN: apomorphine, ketamine, melphalan. MCT1 FN: pravastatin. MRP2 FN: baicalin, bromosulfophthalein, furosemide, naringin. MRP4 FP: amoxicillin. MRP4 FN: azathioprine, chlorothiazide, ciprofloxacin, dasatinib, etoposide, folate, imatinib, olmesartan, teniposide, topotecan, valsartan. OATP2B1 FN: dheas, talinolol. PGP FN: alprazolam, budesonide, cyclosporine, dolasetron, fentanyl, granisetron, palonosetron, prednisone, quinidine, tacrolimus.
3. Intestinal Absorption (Gut)90.1% accuracy
Validated transporters across enterocytes lining the gastrointestinal tract. Apical efflux (PGP, BCRP, MRP2) limits oral bioavailability. Influx transporters (PEPT1, OATP2B1, CNT2, MCT1) facilitate drug absorption.
| Transporter | N | TP | TN | FP | FN | Sens | Spec | Acc |
|---|---|---|---|---|---|---|---|---|
| BCRP | 63 | 30 | 26 | 4 | 3 | 90.9% | 86.7% | 88.9% |
| CNT2 | 76 | 48 | 24 | 2 | 2 | 96.0% | 92.3% | 94.7% |
| MCT1 | 36 | 25 | 11 | 0 | 0 | 100.0% | 100.0% | 100.0% |
| MCT4 | 49 | 22 | 26 | 0 | 1 | 95.7% | 100.0% | 98.0% |
| MRP2 | 27 | 15 | 8 | 0 | 4 | 78.9% | 100.0% | 85.2% |
| OATP1A2 | 45 | 30 | 10 | 1 | 4 | 88.2% | 90.9% | 88.9% |
| OATP2B1 | 52 | 18 | 25 | 2 | 7 | 72.0% | 92.6% | 82.7% |
| OCT1* | 3 | 3 | 0 | 0 | 0 | 100.0% | — | 100.0% |
| PEPT1 | 49 | 16 | 24 | 2 | 7 | 69.6% | 92.3% | 81.6% |
| PGP | 54 | 22 | 26 | 2 | 4 | 84.6% | 92.9% | 88.9% |
| TOTAL | 454 | 229 | 180 | 13 | 32 | 87.7% | 93.3% | 90.1% |
* Sample size is too small (N < 25); interpret these transporter-specific results cautiously.
Misclassified drugs
Misclassified drugs: BCRP FP: fluconazole, furosemide, loperamide, warfarin. BCRP FN: carboplatin, cisplatin, oxaliplatin. CNT2 FP: acyclovir, tenofovir. CNT2 FN: showdomycin, tegafur. MCT4 FN: simvastatin_acid. MRP2 FN: cisplatin, furosemide, indomethacin, telmisartan. OATP1A2 FP: lopinavir. OATP1A2 FN: ciprofloxacin, gatifloxacin, levofloxacin, telmisartan. OATP2B1 FP: dabigatran, penicillin_v. OATP2B1 FN: aliskiren, bromosulfophthalein, ciprofloxacin, dheas, levofloxacin, sorafenib, sulfasalazine. PEPT1 FP: atenolol, furosemide. PEPT1 FN: 5_aminolevulinic_acid, benzylpenicillin, cefdinir, cefixime, ceftibuten, fosinopril, oseltamivir. PGP FP: amlodipine, pioglitazone. PGP FN: amitriptyline, carboplatin, cisplatin, morphine.
4. Hepatic Transporters87.4% accuracy
Validated transporters across hepatocytes governing drug uptake, biliary excretion, and DILI risk. Sinusoidal uptake (OATP1B1/1B3/2B1, OCT1) and canalicular efflux (PGP, BCRP, MRP2, BSEP, MRP4).
| Transporter | N | TP | TN | FP | FN | Sens | Spec | Acc |
|---|---|---|---|---|---|---|---|---|
| BCRP | 35 | 25 | 9 | 1 | 0 | 100.0% | 90.0% | 97.1% |
| BSEP | 33 | 2 | 30 | 1 | 0 | 100.0% | 96.8% | 97.0% |
| MRP2 | 32 | 7 | 16 | 0 | 9 | 43.8% | 100.0% | 71.9% |
| MRP4 | 57 | 23 | 28 | 2 | 4 | 85.2% | 93.3% | 89.5% |
| OATP1B1* | 23 | 6 | 12 | 1 | 4 | 60.0% | 92.3% | 78.3% |
| OATP1B3* | 23 | 0 | 14 | 0 | 9 | 0.0% | 100.0% | 60.9% |
| OATP2B1* | 13 | 0 | 8 | 0 | 5 | 0.0% | 100.0% | 61.5% |
| OCT1 | 32 | 22 | 9 | 1 | 0 | 100.0% | 90.0% | 96.9% |
| PGP | 77 | 47 | 26 | 1 | 3 | 94.0% | 96.3% | 94.8% |
| TOTAL | 325 | 132 | 152 | 7 | 34 | 79.5% | 95.6% | 87.4% |
* Sample size is too small (N < 25); interpret these transporter-specific results cautiously.
Misclassified drugs
Misclassified drugs: BCRP FP: ibuprofen. BSEP FP: fluvastatin. MRP2 FN: atorvastatin, ceftriaxone, diclofenac, ibuprofen, naproxen, rosuvastatin, sulfamethoxazole, sulfasalazine, trimethoprim. MRP4 FP: imatinib, rosuvastatin. MRP4 FN: benzylpenicillin, cefazolin, diclofenac, indomethacin. OATP1B1 FP: amoxicillin. OATP1B1 FN: bosentan, repaglinide, rifampicin, valsartan. OATP1B3 FN: atorvastatin, bosentan, fluvastatin, olmesartan, pitavastatin, pravastatin, rifampicin, rosuvastatin, telmisartan. OATP2B1 FN: atorvastatin, fexofenadine, fluvastatin, montelukast, rosuvastatin. OCT1 FP: ampicillin. PGP FP: piroxicam. PGP FN: atorvastatin, palonosetron, tipranavir.
5. Breast Milk Transfer94.1% accuracy
Validated transporters across mammary epithelial cells. Concentrating transporters (BCRP, OCT1, CNT1/3, MRP2, MATE1) may accumulate drug in milk.
| Transporter | N | TP | TN | FP | FN | Sens | Spec | Acc |
|---|---|---|---|---|---|---|---|---|
| BCRP | 69 | 31 | 34 | 2 | 2 | 93.9% | 94.4% | 94.2% |
| CNT1 | 49 | 23 | 22 | 2 | 2 | 92.0% | 91.7% | 91.8% |
| CNT3 | 50 | 25 | 25 | 0 | 0 | 100.0% | 100.0% | 100.0% |
| ENT1 | 70 | 15 | 54 | 0 | 1 | 93.8% | 100.0% | 98.6% |
| MATE1 | 47 | 25 | 22 | 0 | 0 | 100.0% | 100.0% | 100.0% |
| MRP1 | 47 | 15 | 29 | 3 | 0 | 100.0% | 90.6% | 93.6% |
| MRP2 | 63 | 22 | 30 | 9 | 2 | 91.7% | 76.9% | 82.5% |
| OCT1 | 47 | 23 | 18 | 4 | 2 | 92.0% | 81.8% | 87.2% |
| OCT2* | 10 | 6 | 4 | 0 | 0 | 100.0% | 100.0% | 100.0% |
| PGP | 77 | 49 | 26 | 1 | 1 | 98.0% | 96.3% | 97.4% |
| TOTAL | 529 | 234 | 264 | 21 | 10 | 95.9% | 92.6% | 94.1% |
* Sample size is too small (N < 25); interpret these transporter-specific results cautiously.
Misclassified drugs
Misclassified drugs: BCRP FP: elvitegravir, entecavir. BCRP FN: gemifloxacin, lapatinib. CNT1 FP: cladribine, fludarabine. CNT1 FN: emtricitabine, tegafur. ENT1 FN: sofosbuvir. MRP1 FP: bromocriptine, ledipasvir, posaconazole. MRP2 FP: bromocriptine, clindamycin, epirubicin, itraconazole, lapatinib, lopinavir, nilotinib, ponatinib, posaconazole. MRP2 FN: cdcf, cisplatin. OCT1 FP: amoxicillin, clindamycin, erythromycin, verapamil. OCT1 FN: lamotrigine, ondansetron. PGP FP: piroxicam. PGP FN: cisplatin.
6. Placental Barrier94.6% accuracy
Validated transporters across syncytiotrophoblast barrier. Protective efflux (PGP, MRP1, MRP2) limits fetal exposure. Influx/bidirectional transporters (ENT, LAT1, OATP2B1) may increase transfer.
| Transporter | N | TP | TN | FP | FN | Sens | Spec | Acc |
|---|---|---|---|---|---|---|---|---|
| ENT | 65 | 12 | 53 | 0 | 0 | 100.0% | 100.0% | 100.0% |
| LAT1* | 19 | 8 | 10 | 0 | 1 | 88.9% | 100.0% | 94.7% |
| MRP1 | 43 | 12 | 28 | 3 | 0 | 100.0% | 90.3% | 93.0% |
| MRP2 | 32 | 15 | 15 | 1 | 1 | 93.8% | 93.8% | 93.8% |
| MRP5 | 30 | 8 | 19 | 1 | 2 | 80.0% | 95.0% | 90.0% |
| OATP2B1 | 49 | 22 | 24 | 0 | 3 | 88.0% | 100.0% | 93.9% |
| PGP | 77 | 48 | 24 | 3 | 2 | 96.0% | 88.9% | 93.5% |
| TOTAL | 315 | 125 | 173 | 8 | 9 | 93.3% | 95.6% | 94.6% |
* Sample size is too small (N < 25); interpret these transporter-specific results cautiously.
Misclassified drugs
Misclassified drugs: LAT1 FN: apomorphine. MRP1 FP: bromocriptine, ledipasvir, posaconazole. MRP2 FP: diltiazem. MRP2 FN: pravastatin. MRP5 FP: acyclovir. MRP5 FN: indomethacin, thioguanine. OATP2B1 FN: aliskiren, ciprofloxacin, levofloxacin. PGP FP: diazepam, lidocaine_topical, piroxicam. PGP FN: atorvastatin, cisplatin.
7. Pulmonary93.1% accuracy
Validated transporters across pulmonary epithelial cells. MRP1 (basolateral efflux) and MRP5 (intracellular) affect inhaled drug distribution.
| Transporter | N | TP | TN | FP | FN | Sens | Spec | Acc |
|---|---|---|---|---|---|---|---|---|
| BCRP | 53 | 32 | 14 | 6 | 1 | 97.0% | 70.0% | 86.8% |
| MRP1 | 43 | 9 | 31 | 0 | 3 | 75.0% | 100.0% | 93.0% |
| MRP5 | 30 | 7 | 19 | 1 | 3 | 70.0% | 95.0% | 86.7% |
| PGP | 77 | 50 | 27 | 0 | 0 | 100.0% | 100.0% | 100.0% |
| TOTAL | 203 | 98 | 91 | 7 | 7 | 93.3% | 92.9% | 93.1% |
Misclassified drugs
Misclassified drugs: BCRP FP: bromocriptine, ceritinib, ibuprofen, itraconazole, piperaquine, posaconazole. BCRP FN: epirubicin. MRP1 FN: bilirubin_glucuronide, estrone_3_sulfate, ritonavir. MRP5 FP: acyclovir. MRP5 FN: indomethacin, mercaptopurine, thioguanine.
8. Retinal / Ocular92.7% accuracy
Validated transporters across the blood-retinal barrier. MRP1 (outer BRB/RPE) and MRP5 (intracellular) limit ocular drug penetration.
| Transporter | N | TP | TN | FP | FN | Sens | Spec | Acc |
|---|---|---|---|---|---|---|---|---|
| BCRP | 53 | 32 | 14 | 6 | 1 | 97.0% | 70.0% | 86.8% |
| MRP1 | 43 | 12 | 31 | 0 | 0 | 100.0% | 100.0% | 100.0% |
| MRP4 | 57 | 19 | 27 | 3 | 8 | 70.4% | 90.0% | 80.7% |
| MRP5 | 30 | 9 | 20 | 0 | 1 | 90.0% | 100.0% | 96.7% |
| PGP | 77 | 50 | 27 | 0 | 0 | 100.0% | 100.0% | 100.0% |
| TOTAL | 260 | 122 | 119 | 9 | 10 | 92.4% | 93.0% | 92.7% |
Misclassified drugs
Misclassified drugs: BCRP FP: bromocriptine, ceritinib, ibuprofen, itraconazole, piperaquine, posaconazole. BCRP FN: epirubicin. MRP4 FP: aspirin, caffeine, gabapentin. MRP4 FN: alprostadil, benzylpenicillin, cidofovir, diclofenac, dinoprostone, indomethacin, leucovorin, torsemide. MRP5 FN: indomethacin.
9. Renal Clearance89.8% accuracy
Validated transporters across proximal tubular cells. Basolateral uptake (OCT2, OAT1, OAT3) and apical efflux (MATE1, MATE2K, MRP4) govern active renal secretion.
| Transporter | N | TP | TN | FP | FN | Sens | Spec | Acc |
|---|---|---|---|---|---|---|---|---|
| MATE1 | 30 | 18 | 11 | 1 | 0 | 100.0% | 91.7% | 96.7% |
| MATE2K | 30 | 19 | 9 | 1 | 1 | 95.0% | 90.0% | 93.3% |
| MRP2 | 32 | 10 | 16 | 0 | 6 | 62.5% | 100.0% | 81.2% |
| MRP4 | 26 | 17 | 7 | 0 | 2 | 89.5% | 100.0% | 92.3% |
| OAT1 | 39 | 20 | 15 | 3 | 1 | 95.2% | 83.3% | 89.7% |
| OAT3 | 39 | 21 | 12 | 4 | 2 | 91.3% | 75.0% | 84.6% |
| OCT2 | 39 | 29 | 7 | 2 | 1 | 96.7% | 77.8% | 92.3% |
| TOTAL | 235 | 134 | 77 | 11 | 13 | 91.2% | 87.5% | 89.8% |
Misclassified drugs
Misclassified drugs: MATE1 FP: ranitidine. MATE2K FP: ranitidine. MATE2K FN: berberine. MRP2 FN: ciprofloxacin, diclofenac, ibuprofen, naproxen, norfloxacin, trimethoprim. MRP4 FN: benzylpenicillin, cefazolin. OAT1 FP: cefadroxil, gabapentin, pravastatin. OAT1 FN: lamivudine. OAT3 FP: atorvastatin, cefaclor, gabapentin, tenofovir. OAT3 FN: ranitidine, torsemide. OCT2 FP: lisinopril, quinine. OCT2 FN: tenofovir.
Validation Protocol
Leave-none-out validation: every drug with ground truth is screened by the engine and compared against curated literature labels. No drug is excluded from the denominator unless the SMILES string is incomplete.
Data Sources
Ground Truth: Curated from UCSF-FDA TransPortal, DrugBank and primary literature. All data processed as SMILES strings.