This directory contains:
Python modules with methods used in this directory
The notebook for training the $\mathrm{A}_{1}\mathrm{AR}$ and $\mathrm{MR}$ models
The hyperparameter optimization studies, stored in the optuna_studies_dbs directory
The optimized $\mathrm{MR}$ and $\mathrm{A}_{1}\mathrm{AR}$ serialized models, found in the qsprModels directory
The notebook for performing the virtual screening
The notebook for analyzing the spheroid swelling results on the ADPKD phenotypic assay
The modules/ directory contains supporting Python code used by the notebooks:
hparam_optimization.py — Optuna-based hyperparameter optimization for QSPRpred modelsknn.py — k-Nearest Neighbors distance computation for applicability domain analysismood_qsprpred_splits.py — QSPRpred-compatible split adapters retained from model development. The committed notebook uses only the exported scikit-learn ShuffleSplit; optional MOOD adapters are not part of the locked environment.qspr_xgb.py — XGBoost regression model wrapper for QSPRpredregression_plot.py — Predicted vs. observed regression plots
Virtual Screening Results These are the compounds selected for phenotypic screening based on the virtual screening results. For $\mathrm{A}_{1}\mathrm{AR}$ , task variable consisted of solely pKi activity values, while for $\mathrm{MR}$ , the training data consisted of both pIC50 and pKi values. These predicted values are represented as pChEMBL, as a placeholder for the -log10 transformed predicted activity values.
Target
Compound ID
Structure
Predicted pChEMBL value
ADORA1
824745
8.45
ADORA1
1237561
7.1
ADORA1
1249141
7.27
ADORA1
1823372
7.53
ADORA1
22755240
7.13
ADORA1
27070328
7.75
NR3C2
Z95680027
7.32
NR3C2
Z318400112
7.33
NR3C2
Z90308949
7.09
DPCPX - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=12$ )
DPCPX 0.001µM, ($N=4$ )
0.2121
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=12$ )
DPCPX 0.1µM, ($N=4$ )
0.0297
*
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=12$ )
DPCPX 1µM, ($N=4$ )
0.0132
*
$\mathrm{A}_{1}\mathrm{AR}$
DPCPX 0.001µM CPA 1µM, ($N=4$ )
DPCPX 0.1µM CPA 1µM, ($N=4$ )
0.1143
ns
$\mathrm{A}_{1}\mathrm{AR}$
DPCPX 0.001µM CPA 1µM, ($N=4$ )
DPCPX 1µM CPA 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
DPCPX 0.001µM, ($N=4$ )
DPCPX 0.1µM, ($N=4$ )
0.6857
ns
$\mathrm{A}_{1}\mathrm{AR}$
DPCPX 0.001µM, ($N=4$ )
DPCPX 1µM, ($N=4$ )
0.1143
ns
$\mathrm{A}_{1}\mathrm{AR}$
DPCPX 0.1µM, ($N=4$ )
DPCPX 1µM, ($N=4$ )
0.4857
ns
$\mathrm{A}_{1}\mathrm{AR}$
Capadenoson - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=12$ )
Capadenoson 0.001µM, ($N=4$ )
0.0011
**
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=12$ )
Capadenoson 0.1µM, ($N=4$ )
0.0011
**
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=12$ )
Capadenoson 1µM, ($N=4$ )
0.0011
**
$\mathrm{A}_{1}\mathrm{AR}$
Capadenoson 0.001µM CPA 1µM, ($N=4$ )
Capadenoson 0.1µM CPA 1µM, ($N=4$ )
0.2
ns
$\mathrm{A}_{1}\mathrm{AR}$
Capadenoson 0.001µM CPA 1µM, ($N=4$ )
Capadenoson 1µM CPA 1µM, ($N=4$ )
0.2
ns
$\mathrm{A}_{1}\mathrm{AR}$
Capadenoson 0.001µM, ($N=4$ )
Capadenoson 0.1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
Capadenoson 0.001µM, ($N=4$ )
Capadenoson 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
Capadenoson 0.1µM, ($N=4$ )
Capadenoson 1µM, ($N=4$ )
0.4857
ns
$\mathrm{A}_{1}\mathrm{AR}$
MIPS521 - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=12$ )
MIPS521 0.001µM, ($N=4$ )
0.4462
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=12$ )
MIPS521 0.1µM, ($N=4$ )
0.0011
**
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=12$ )
MIPS521 1µM, ($N=4$ )
0.0011
**
$\mathrm{A}_{1}\mathrm{AR}$
MIPS521 0.001µM CPA 1µM, ($N=4$ )
MIPS521 0.1µM CPA 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
MIPS521 0.001µM CPA 1µM, ($N=4$ )
MIPS521 1µM CPA 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
MIPS521 0.001µM, ($N=4$ )
MIPS521 0.1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
MIPS521 0.001µM, ($N=4$ )
MIPS521 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
MIPS521 0.1µM, ($N=4$ )
MIPS521 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
824745 - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
824745 0.001µM, ($N=4$ )
0.6167
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
824745 0.1µM, ($N=4$ )
0.4941
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
824745 1µM, ($N=4$ )
0.0801
ns
$\mathrm{A}_{1}\mathrm{AR}$
824745 0.001µM CPA 1µM, ($N=4$ )
824745 0.1µM CPA 1µM, ($N=4$ )
0.2
ns
$\mathrm{A}_{1}\mathrm{AR}$
824745 0.001µM CPA 1µM, ($N=4$ )
824745 1µM CPA 1µM, ($N=4$ )
0.4857
ns
$\mathrm{A}_{1}\mathrm{AR}$
824745 0.001µM, ($N=4$ )
824745 0.1µM, ($N=4$ )
0.8857
ns
$\mathrm{A}_{1}\mathrm{AR}$
824745 0.001µM, ($N=4$ )
824745 1µM, ($N=4$ )
0.1143
ns
$\mathrm{A}_{1}\mathrm{AR}$
824745 0.1µM, ($N=4$ )
824745 1µM, ($N=4$ )
0.1143
ns
$\mathrm{A}_{1}\mathrm{AR}$
1237561 - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
1237561 0.001µM, ($N=4$ )
0.2485
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
1237561 0.1µM, ($N=4$ )
0.9635
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
1237561 1µM, ($N=4$ )
0.2902
ns
$\mathrm{A}_{1}\mathrm{AR}$
1237561 0.001µM CPA 1µM, ($N=4$ )
1237561 0.1µM CPA 1µM, ($N=4$ )
0.3429
ns
$\mathrm{A}_{1}\mathrm{AR}$
1237561 0.001µM CPA 1µM, ($N=4$ )
1237561 1µM CPA 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
1237561 0.001µM, ($N=4$ )
1237561 0.1µM, ($N=4$ )
0.4857
ns
$\mathrm{A}_{1}\mathrm{AR}$
1237561 0.001µM, ($N=4$ )
1237561 1µM, ($N=4$ )
0.8857
ns
$\mathrm{A}_{1}\mathrm{AR}$
1237561 0.1µM, ($N=4$ )
1237561 1µM, ($N=4$ )
0.3429
ns
$\mathrm{A}_{1}\mathrm{AR}$
1249141 - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
1249141 0.001µM, ($N=4$ )
0.4372
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
1249141 0.1µM, ($N=4$ )
0.9635
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
1249141 1µM, ($N=4$ )
0.0029
**
$\mathrm{A}_{1}\mathrm{AR}$
1249141 0.001µM CPA 1µM, ($N=4$ )
1249141 0.1µM CPA 1µM, ($N=4$ )
0.8857
ns
$\mathrm{A}_{1}\mathrm{AR}$
1249141 0.001µM CPA 1µM, ($N=4$ )
1249141 1µM CPA 1µM, ($N=4$ )
0.2
ns
$\mathrm{A}_{1}\mathrm{AR}$
1249141 0.001µM, ($N=4$ )
1249141 0.1µM, ($N=4$ )
0.3429
ns
$\mathrm{A}_{1}\mathrm{AR}$
1249141 0.001µM, ($N=4$ )
1249141 1µM, ($N=4$ )
0.1143
ns
$\mathrm{A}_{1}\mathrm{AR}$
1249141 0.1µM, ($N=4$ )
1249141 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
1823372 - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
1823372 0.001µM, ($N=4$ )
0.0219
*
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
1823372 0.1µM, ($N=4$ )
0.6819
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
1823372 1µM, ($N=4$ )
0.2902
ns
$\mathrm{A}_{1}\mathrm{AR}$
1823372 0.001µM CPA 1µM, ($N=4$ )
1823372 0.1µM CPA 1µM, ($N=4$ )
0.6857
ns
$\mathrm{A}_{1}\mathrm{AR}$
1823372 0.001µM CPA 1µM, ($N=4$ )
1823372 1µM CPA 1µM, ($N=4$ )
0.1143
ns
$\mathrm{A}_{1}\mathrm{AR}$
1823372 0.001µM, ($N=4$ )
1823372 0.1µM, ($N=4$ )
0.1143
ns
$\mathrm{A}_{1}\mathrm{AR}$
1823372 0.001µM, ($N=4$ )
1823372 1µM, ($N=4$ )
0.1143
ns
$\mathrm{A}_{1}\mathrm{AR}$
1823372 0.1µM, ($N=4$ )
1823372 1µM, ($N=4$ )
0.6857
ns
$\mathrm{A}_{1}\mathrm{AR}$
22755240 - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
22755240 0.001µM, ($N=4$ )
0.1775
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
22755240 0.1µM, ($N=4$ )
0.4941
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
22755240 1µM, ($N=4$ )
0.0995
ns
$\mathrm{A}_{1}\mathrm{AR}$
22755240 0.001µM CPA 1µM, ($N=4$ )
22755240 0.1µM CPA 1µM, ($N=4$ )
0.2
ns
$\mathrm{A}_{1}\mathrm{AR}$
22755240 0.001µM CPA 1µM, ($N=4$ )
22755240 1µM CPA 1µM, ($N=4$ )
0.8857
ns
$\mathrm{A}_{1}\mathrm{AR}$
22755240 0.001µM, ($N=4$ )
22755240 0.1µM, ($N=4$ )
0.8857
ns
$\mathrm{A}_{1}\mathrm{AR}$
22755240 0.001µM, ($N=4$ )
22755240 1µM, ($N=4$ )
0.6857
ns
$\mathrm{A}_{1}\mathrm{AR}$
22755240 0.1µM, ($N=4$ )
22755240 1µM, ($N=4$ )
0.3429
ns
$\mathrm{A}_{1}\mathrm{AR}$
27070328 - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
27070328 0.001µM, ($N=4$ )
0.1775
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
27070328 0.1µM, ($N=4$ )
0.1218
ns
$\mathrm{A}_{1}\mathrm{AR}$
FSK 2.5µM, ($N=16$ )
27070328 1µM, ($N=4$ )
0.0111
*
$\mathrm{A}_{1}\mathrm{AR}$
27070328 0.001µM CPA 1µM, ($N=4$ )
27070328 0.1µM CPA 1µM, ($N=4$ )
0.0571
ns
$\mathrm{A}_{1}\mathrm{AR}$
27070328 0.001µM CPA 1µM, ($N=4$ )
27070328 1µM CPA 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
27070328 0.001µM, ($N=4$ )
27070328 0.1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
27070328 0.001µM, ($N=4$ )
27070328 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
27070328 0.1µM, ($N=4$ )
27070328 1µM, ($N=4$ )
0.0286
*
$\mathrm{A}_{1}\mathrm{AR}$
Finerenone - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
Finerenone 0.001µM, ($N=4$ )
0.1218
ns
MR
FSK 2.5µM, ($N=16$ )
Finerenone 0.1µM, ($N=4$ )
0.064
ns
MR
FSK 2.5µM, ($N=16$ )
Finerenone 1µM, ($N=4$ )
0.0111
*
MR
Finerenone 0.001µM Aldosterone 1µM, ($N=4$ )
Finerenone 0.1µM Aldosterone 1µM, ($N=4$ )
0.6857
ns
MR
Finerenone 0.001µM Aldosterone 1µM, ($N=4$ )
Finerenone 1µM Aldosterone 1µM, ($N=4$ )
0.0286
*
MR
Finerenone 0.001µM, ($N=4$ )
Finerenone 0.1µM, ($N=4$ )
0.8857
ns
MR
Finerenone 0.001µM, ($N=4$ )
Finerenone 1µM, ($N=4$ )
0.3429
ns
MR
Finerenone 0.1µM, ($N=4$ )
Finerenone 1µM, ($N=4$ )
0.4857
ns
MR
Esaxerenone - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
Esaxerenone 0.001µM, ($N=4$ )
0.2902
ns
MR
FSK 2.5µM, ($N=16$ )
Esaxerenone 0.1µM, ($N=4$ )
0.8916
ns
MR
FSK 2.5µM, ($N=16$ )
Esaxerenone 1µM, ($N=4$ )
0.0293
*
MR
Esaxerenone 0.001µM Aldosterone 1µM, ($N=4$ )
Esaxerenone 0.1µM Aldosterone 1µM, ($N=4$ )
0.1143
ns
MR
Esaxerenone 0.001µM Aldosterone 1µM, ($N=4$ )
Esaxerenone 1µM Aldosterone 1µM, ($N=4$ )
0.0571
ns
MR
Esaxerenone 0.001µM, ($N=4$ )
Esaxerenone 0.1µM, ($N=4$ )
0.6857
ns
MR
Esaxerenone 0.001µM, ($N=4$ )
Esaxerenone 1µM, ($N=4$ )
0.0286
*
MR
Esaxerenone 0.1µM, ($N=4$ )
Esaxerenone 1µM, ($N=4$ )
0.2
ns
MR
Apararenone - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
Apararenone 0.001µM, ($N=4$ )
0.4941
ns
MR
FSK 2.5µM, ($N=16$ )
Apararenone 0.1µM, ($N=4$ )
0.9635
ns
MR
FSK 2.5µM, ($N=16$ )
Apararenone 1µM, ($N=4$ )
0.5536
ns
MR
Apararenone 0.001µM Aldosterone 1µM, ($N=4$ )
Apararenone 0.1µM Aldosterone 1µM, ($N=4$ )
0.4857
ns
MR
Apararenone 0.001µM Aldosterone 1µM, ($N=4$ )
Apararenone 1µM Aldosterone 1µM, ($N=4$ )
0.2
ns
MR
Apararenone 0.001µM, ($N=4$ )
Apararenone 0.1µM, ($N=4$ )
0.8857
ns
MR
Apararenone 0.001µM, ($N=4$ )
Apararenone 1µM, ($N=4$ )
1
ns
MR
Apararenone 0.1µM, ($N=4$ )
Apararenone 1µM, ($N=4$ )
0.8857
ns
MR
Benidipine - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
Benidipine 0.001µM, ($N=4$ )
0.3847
ns
MR
FSK 2.5µM, ($N=16$ )
Benidipine 0.1µM, ($N=4$ )
0.4372
ns
MR
FSK 2.5µM, ($N=16$ )
Benidipine 1µM, ($N=4$ )
0.2902
ns
MR
Benidipine 0.001µM Aldosterone 1µM, ($N=4$ )
Benidipine 0.1µM Aldosterone 1µM, ($N=4$ )
0.8857
ns
MR
Benidipine 0.001µM Aldosterone 1µM, ($N=4$ )
Benidipine 1µM Aldosterone 1µM, ($N=4$ )
0.3429
ns
MR
Benidipine 0.001µM, ($N=4$ )
Benidipine 0.1µM, ($N=4$ )
0.8857
ns
MR
Benidipine 0.001µM, ($N=4$ )
Benidipine 1µM, ($N=4$ )
0.2
ns
MR
Benidipine 0.1µM, ($N=4$ )
Benidipine 1µM, ($N=4$ )
0.1143
ns
MR
Z318400112 - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
Z318400112 0.001µM, ($N=4$ )
0.4941
ns
MR
FSK 2.5µM, ($N=16$ )
Z318400112 0.1µM, ($N=4$ )
0.1482
ns
MR
FSK 2.5µM, ($N=16$ )
Z318400112 1µM, ($N=4$ )
0.1482
ns
MR
Z318400112 0.001µM Aldosterone 1µM, ($N=4$ )
Z318400112 0.1µM Aldosterone 1µM, ($N=4$ )
0.0286
*
MR
Z318400112 0.001µM Aldosterone 1µM, ($N=4$ )
Z318400112 1µM Aldosterone 1µM, ($N=4$ )
0.4857
ns
MR
Z318400112 0.001µM, ($N=4$ )
Z318400112 0.1µM, ($N=4$ )
0.6857
ns
MR
Z318400112 0.001µM, ($N=4$ )
Z318400112 1µM, ($N=4$ )
0.4857
ns
MR
Z318400112 0.1µM, ($N=4$ )
Z318400112 1µM, ($N=4$ )
1
ns
MR
Z90308949 - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
Z90308949 0.001µM, ($N=4$ )
0.0801
ns
MR
FSK 2.5µM, ($N=16$ )
Z90308949 0.1µM, ($N=4$ )
0.9635
ns
MR
FSK 2.5µM, ($N=16$ )
Z90308949 1µM, ($N=4$ )
0.1482
ns
MR
Z90308949 0.001µM Aldosterone 1µM, ($N=4$ )
Z90308949 0.1µM Aldosterone 1µM, ($N=4$ )
0.8857
ns
MR
Z90308949 0.001µM Aldosterone 1µM, ($N=4$ )
Z90308949 1µM Aldosterone 1µM, ($N=4$ )
0.2
ns
MR
Z90308949 0.001µM, ($N=4$ )
Z90308949 0.1µM, ($N=4$ )
0.2
ns
MR
Z90308949 0.001µM, ($N=4$ )
Z90308949 1µM, ($N=4$ )
0.0571
ns
MR
Z90308949 0.1µM, ($N=4$ )
Z90308949 1µM, ($N=4$ )
0.2
ns
MR
Z95680027 - Simulant (FSK) dose: 2.5µM
group1
group2
pvalue
symbol
target
FSK 2.5µM, ($N=16$ )
Z95680027 0.001µM, ($N=4$ )
0.5536
ns
MR
FSK 2.5µM, ($N=16$ )
Z95680027 0.1µM, ($N=4$ )
0.6167
ns
MR
FSK 2.5µM, ($N=16$ )
Z95680027 1µM, ($N=4$ )
0.0074
**
MR
Z95680027 0.001µM Aldosterone 1µM, ($N=4$ )
Z95680027 0.1µM Aldosterone 1µM, ($N=4$ )
0.0286
*
MR
Z95680027 0.001µM Aldosterone 1µM, ($N=4$ )
Z95680027 1µM Aldosterone 1µM, ($N=4$ )
0.0286
*
MR
Z95680027 0.001µM, ($N=4$ )
Z95680027 0.1µM, ($N=4$ )
1
ns
MR
Z95680027 0.001µM, ($N=4$ )
Z95680027 1µM, ($N=4$ )
0.0286
*
MR
Z95680027 0.1µM, ($N=4$ )
Z95680027 1µM, ($N=4$ )
0.0286
*
MR
