Large-scale synthetic data enable digital twins of human excitable cells.
The 6 matches
- [1] § Methods › Training and loss function ↔ network/iPSC_training/test21/DL1.py, lines 135–197 · score 0.66 · Keras, monitored, metrics, absolute, batches, epoch
- [2] § Methods › Training and loss function ↔ network/iPSC_training/test21/DL1.py, lines 135–197 · score 0.59 · squared error, Adam, loss, metric, optimizer, trained
- [3] § Methods › iPSC-CM electrophysiological model ↔ Fig5_experiments_vs_model/simulated/fig5A_sim/ipsc_function.h, lines 18–67 · score 0.54 · Kernik Clancy, CM model, variables, iPSC, gating, IKs
- [4] § Methods › iPSC-CM electrophysiological model ↔ Fig5_experiments_vs_model/simulated/fig5B_sim/ipsc_function.h, lines 18–67 · score 0.54 · Kernik Clancy, CM model, variables, iPSC, gating, IKs
- [5] § Results › Deep learning approaches for voltage clamp optimization and parameter estimation ↔ network/iPSC_training/test21/DL1.py, lines 200–254 · score 0.53 · absolute error, error distribution, epochs, predictive, training, network
- [6] § Results › Deep learning approaches for voltage clamp optimization and parameter estimation ↔ network/iPSC_training/ipsc_function.h, lines 1–17 · score 0.51 · induced pluripotent stem, cell derived cardiomyocytes, model parameters, iPSC, network, training
Paper
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The authors' code
Python · 254 lines · 8 KB · CC-BY-NC-4.0 · 3 matches
- #Created by Mao-Tsuen Jeng
- #Colleen Clancy Lab @ UC davis
- import tensorflow as tf
- import numpy as np
- import tensorflow.keras as keras
- from matplotlib import pyplot as plt
- import pickle
- import os
- import glob
- #import csv
- from tensorflow.keras.models import Sequential, Model
- #from keras.layers.core import Dense, Dropout, Activation
- from tensorflow.keras.layers import Dense, Dropout, Activation, LSTM, SimpleRNN
- from tensorflow.keras.optimizers import SGD, Adagrad
- from tensorflow.keras import layers
- from tensorflow.keras.optimizers import RMSprop
- from tensorflow.keras.callbacks import EarlyStopping
- from tensorflow.keras.utils import plot_model
- from tensorflow.python.client import device_lib
- print(device_lib.list_local_devices())
- #from tensorflow.keras import backend as K
- #K.tensorflow_backend._get_available_gpus()
- idxs = np.arange(0, 7625, 1 )
- l1 = np.size(idxs)
- lt = l1
- # This determines the number of inputs
- #x = np.zeros((n, lt))
- x1= np.zeros((1, lt))
- # This determines the number of outputs
- sy = 52
- #y = np.zeros((n, sy))
- y1 = np.zeros((1, sy))
- foldername = '../valid'
- filename = foldername + '/itotal_cell1' + '.txt'
- raw_data = open( filename, 'rt' )
- data = np.loadtxt( raw_data, delimiter='\t')
- raw_data.close()
- id1 = 0
- x1[id1, 0:l1] = data[idxs]
- filename3 = foldername + '/parameters_cell1' + '.txt'
- raw_data = open( filename3, 'rt' )
- data3 = np.loadtxt( raw_data, delimiter='\t')
- raw_data.close()
- y1[id1,:] = data3[:]
- x = np.load('../itotal_all.npy')
- y = np.load('../parameters_all.npy')
- n = x.shape[0]
- n1 = 0
- id2 = 0
- tf.keras.backend.set_floatx('float64')
- nk = 1024 # sy * 16
- model = Sequential()
- model.add(Dense(nk, input_shape=(lt, ), activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(nk, activation='tanh', dtype=tf.float64))
- model.add(Dense(sy, activation='linear', dtype=tf.float64))
- batch_size = np.round(n*0.01) #10000
- n1= np.round(n*0.1).astype(int) #100000
- input_size = n - 3 * n1
- x_tr = tf.cast(x[0:n-n1*3,], tf.float64)
- y_tr = tf.cast(y[0:n-n1*3,], tf.float64)
- x_val = tf.cast(x[n-3*n1:n-2*n1,], tf.float64)
- y_val = tf.cast(y[n-3*n1:n-2*n1,], tf.float64)
- x_test = tf.cast(x[n-2*n1:n,], tf.float64)
- y_test = tf.cast(y[n-2*n1:n,], tf.float64)
- train_dataset = tf.data.Dataset.from_tensor_slices((x_tr, y_tr))
- train_dataset = train_dataset.shuffle(input_size)
- train_dataset = train_dataset.batch(batch_size).cache()
- train_dataset = train_dataset.prefetch(tf.data.experimental.AUTOTUNE)
- model_wrapper = model
- initial_learning_rate = 0.0001
- lr_schedule = keras.optimizers.schedules.ExponentialDecay(
- initial_learning_rate,
- decay_steps=100,
- decay_rate=0.99,
- staircase=True)
- model_wrapper.compile(
- optimizer=tf.keras.optimizers.Adam(learning_rate=lr_schedule , clipnorm=0.1 ),
- loss=keras.losses.MeanSquaredError(),
- metrics=['accuracy'])
- early_stopping = EarlyStopping(patience=1000, monitor='val_loss' )
- mycallbacks = [
- early_stopping, #EarlyStopping(patience=10, monitor="loss" ),
- tf.keras.callbacks.ModelCheckpoint(
- # Path where to save the model
- # The two parameters below mean that we will overwrite
- # the current checkpoint if and only if
- # the `val_loss` score has improved.
- # The saved model name will include the current epoch.
- filepath="model_{epoch:04d}.keras",
- save_best_only= False, #True, # Only save a model if `val_loss` has improved.
- monitor="val_loss",
- verbose=1
- )
- ]
- history=model_wrapper.fit(train_dataset, epochs=1000, validation_data=(x_val,y_val), callbacks=mycallbacks)
- model_wrapper.save("./last_model.keras")
- filename = f"trainHistoryDict"
- with open(filename, 'wb') as file_pi:
- pickle.dump(history.history, file_pi)
- model_list = glob.glob('model*.keras')
- model_list.sort()
- modellength = model_list.__len__()
- loss_test = np.zeros(modellength)
- for id, mymodel in enumerate(model_list):
- model_wrapper = keras.models.load_model(mymodel)
- print("Evaluate on test data using ", mymodel )
- results = model_wrapper.evaluate(x_test, y_test, batch_size=n1)
- print("test loss, test acc:", results)
- loss_test[id] = results[0]
- id = np.where(loss_test == loss_test.min())[0][0]
- model_wrapper = keras.models.load_model(model_list[id])
- model_wrapper.save("./best_model.keras")
- y2 = model_wrapper.predict(x_test)
- y2d = y2 - y_test
- sy2d = np.sum(np.absolute(y2d),0)
- #mdy = np.mean(np.absolute(y2d),1)
- dy = np.absolute(np.array( y2d ) )
- two_std = np.std(dy,0) * 2
- mdy = np.mean(dy,1)
- my2 = np.mean(y2,1)
- sdy = np.sum(dy,0)
- n = y2.shape[0]
- import plotly.express as px
- fig = px.box(dy)
- #fig.show()
- fig.write_html('error.htm')
- np.savetxt('parameters_abs_errors.txt', dy )
- np.savetxt('test_errors.txt', mdy )
- counts, bins = np.histogram(mdy, bins = 100 )
- np.savetxt('test_errors_counts.txt', counts)
- np.savetxt('test_errors_bins.txt', bins )
- fig0, ax0 = plt.subplots()
- counts, bins = np.histogram(mdy, bins = 100)
- ax0.stairs(counts, bins)
- ax0.set_title('Distribution of fitting')
- ax0.set_xlabel('average absolute error')
- ax0.set_ylabel('amount of samples')
- fig0.savefig('ErrorDistribution')
- np.savetxt( 'hist_test_error.txt', counts )
- fig1, ax1 = plt.subplots()
- ax1.stairs(sy2d/n1/2)
- ax1.set_title('average absolute test error in each parameter ')
- ax1.set_xlabel('parameter #')
- ax1.set_ylabel('average absolute error')
- fig1.savefig('Errors.png')
- np.savetxt('Parameters_mean_errors.txt', sy2d/n1/2 )
- x3 = x1 - x1
- y3 = model_wrapper.predict(x3)
- print("\nPredict Original")
- print(y3)
- np.savetxt('Predict_Original.txt', y3 )
- xn = np.arange(loss_test.size)+1
- fig2, ax2 = plt.subplots()
- ax2.plot(xn[2:], loss_test[2:])
- ax2.plot(xn[2:], history.history['loss'][2:])
- ax2.set_title('model loss')
- ax2.set_ylabel('loss')
- ax2.set_xlabel('epoch')
- ax2.legend(['test_loss', 'loss' ], loc='upper left')
- fig2.savefig('performance.png')
- ett = np.array([xn, loss_test, history.history['loss']]).transpose()
- np.savetxt( 'error_test_train.txt', ett )
DL1.py at commit ca8d421, under CC-BY-NC-4.0 · at the source
Overview
- Center for Precision Medicine and Data Science, University of California, Davis, Davis, United States
- Department of Physiology and Membrane Biology, University of California, Davis, Davis, United States
- Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, Davis, United States
- Institute for Regenerative Cures, University of California, Davis, Davis, United States
- Department of Pharmacology, University of California, Davis, Davis, United States
Abstract
Individual variability shapes how diseases manifest, how patients respond to therapy and how rare phenotypes arise. Conventional experimental approaches obscure variation by averaging which limits mechanistic insight and predictive accuracy. We present a computational framework that builds digital twins of human-induced pluripotent stem cell-derived cardiomyocytes from a single optimized voltage clamp experiment. The framework depends on massive synthetic datasets comprising simulated cells that span broad ionic and electrophysiological ranges. These synthetic data make it possible to control parameters precisely, explore biological variability comprehensively, and train models beyond the limits of experimental data. A neural network trained on synthetic data then inferred biophysical parameters from experimental recordings from live cells, reproducing distinct electrophysiological features. Our study unites computational modeling, data simulation, and learning to enable scalable, precise, individualized cardiac electrophysiology modeling and can be readily extended to any electrically active cell type.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
Its files are read in the Code ↔ Paper reader above, with 6 matches between paragraphs and lines of code.
clancylabucd/digital-twin-for-the-win-personalized-cardiac-electrophysiology
ca8d42172eca1dcbf2e98d0ff7b18ff6ab3e2066, 22 December 2025Availability: 1 check, the latest on 27 September 2026: the link answers
- 27 September 2026: the link answers
17 files
- Fig5_experiments_vs_mode
l/ — MATLAB, 31 linesREADME_plotfig5.m - Fig5_experiments_vs_mode
l/ — C/C++, 152 linessimulated/ fig5A_sim/ integrate_rk2.h - Fig5_experiments_vs_mode
l/ — C/C++, 615 lines, 1 matchsimulated/ fig5A_sim/ ipsc_function.h - Fig5_experiments_vs_mode
l/ — C++, 166 linessimulated/ fig5A_sim/ main_ipsc_baseline.cpp - Fig5_experiments_vs_mode
l/ — C/C++, 152 linessimulated/ fig5B_sim/ integrate_rk2.h - Fig5_experiments_vs_mode
l/ — C/C++, 616 lines, 1 matchsimulated/ fig5B_sim/ ipsc_function.h - Fig5_experiments_vs_mode
l/ — C++, 166 linessimulated/ fig5B_sim/ main_ipsc_baseline.cpp - network/
iPSC_training/ — Python, 120 linescreateData.py - network/
iPSC_training/ — Python, 163 linesexperimental/ experimental_results_tes t.py - network/
iPSC_training/ — Python, 29 linesexperimental/ prepareData.py - network/
iPSC_training/ — C/C++, 152 linesintegrate_rk2.h - network/
iPSC_training/ — C/C++, 683 lines, 1 matchipsc_function.h - network/
iPSC_training/ — C++, 252 linespython_main_ipsc_baselin e.cpp - network/
iPSC_training/ — Python, 254 lines, 3 matchestest21/ DL1.py - network/
runall.sh — Shell, 27 lines - LICENSE.md — License, 5 lines
- README.md — Text, 42 lines
The paper's code and data availability statement is in the Data section.
Tracing map
Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.
What the map holds:
- 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
- 15 scripts, each with its path and the digest of its content;
- 6 matches between paragraphs of the paper and lines of the code (method lexical-v1);
- neither the text of the paper nor the code itself.
Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
No dataset and no data link were found in the paper.
Data availability
Due to the large size of the synthetic datasets (~1.1 M cells), the raw data are not hosted online. However, a representative dataset of 100 cells is provided as an example, and the complete codebase for dataset generation, along with parameter distributions and simulation protocols, is publicly available at GitHub (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 7 authors, 1 keyword, 7 MeSH terms, 4 funders, 56 references.
Cite
This paper
Yang, P.-C., Jeng, M.-T., Lieu, D. K., Smithers, R. L., Hernandez-Hernandez, G., Santana, L. F., & Clancy, C. E. (2026). Large-scale synthetic data enable digital twins of human excitable cells. eLife, 15, RP110013. https://
BibTeX
@article{yang2026large,
author = {Yang, Pei-Chi and Jeng, Mao-Tsuen and Lieu, Deborah K and Smithers, Regan L and Hernandez-Hernandez, Gonzalo and Santana, L Fernando and Clancy, Colleen E},
title = {{Large-scale synthetic data enable digital twins of human excitable cells}},
journal = {eLife},
year = {2026},
month = jul,
volume = {15},
pages = {RP110013},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/
url = {https://
pmid = {42489674},
pmcid = {PMC13395456}
}
RIS
TY - JOUR
AU - Yang, Pei-Chi
AU - Jeng, Mao-Tsuen
AU - Lieu, Deborah K
AU - Smithers, Regan L
AU - Hernandez-Hernandez, Gonzalo
AU - Santana, L Fernando
AU - Clancy, Colleen E
TI - Large-scale synthetic data enable digital twins of human excitable cells
T2 - eLife
J2 - Elife
PY - 2026
DA - 2026/
VL - 15
SP - RP110013
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/
UR - https://
LA - en
ER -
CSL-JSON
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