README.md

hERG paper II: temperature dependence

Study temperature dependence of hERG kinetics.

To reproduce the results in the publication, run the scripts in the order as listed. All scripts under "Paper figures" should reproduce all figures in the publication.

Requirements

• myokit (Myokit)
• pints (Pints)

Above libraries should be installed/included in ../lib/.

Description

Fitting

• fit.py: Simple fitting for a cell; Usage: python fit.py [int:file_id] [str:cell_id] --optional [N_repeats]
• fit.sh: Bash script calling fit.py as a batch from manualselection

Validation

• plot-rmsd-hist.py: Plot fitting and validation (normalised) RMSD histograms for all selected cells (all temperatures)

Manual selection

• manualselection: Contains manual selected cells based on cells selected from QC; manualselected* only based on staircaseramp protocol; manualv2selected* based on manualselected* and validation protocols.

Hierarchical Bayesian Model (HBM)

• pseudo2hbm.py: Run HBM using simplified pseudo-MWG, requires individual cells' fitting results, and plot results

Eyring/Q10

• temperature_models.py: A module contains functions and models for temperature dependence of ion channels, includes generalised Eyring relation and Q10 formulation.

Generate data format for paper figures

• generate-data-fancharts.py: Generate fan charts lines for data to ./out

Paper figures

• paper-rank-cells.py: Rank cells according to the hERG peak under hERG screening protocol (a hERG activation step) for visual purpose only
• paper-demo-eyring-q10.py: Plot demo of Generalised Eyring, Typical Eyring, and Q10 relationships
• paper-fitting-and-validation-recordings-all.py: Plot all selected cells data (both fitting and validation) for all temperatures
• paper-fitting-and-validation-selected-cells-zoom.py: Plot all selected cells model (fitting and validation) against data with zoom-in at selected peaks; require argument file-id
• paper-fitting-and-validation-selected-cells-zoom-run.sh: Run paper-fitting-and-validation-selected-cells-zoom.py for all temperatures
• paper-rmsd-hist.py: Plot RRMSE histograms with best, median, and 90 percentile; require output //rmsd-matrix.txt and //rmsd-matrix-cells.txt from plot-rmsd-hist.py; require argument file-id
• paper-rmsd-hist-run.sh: Run paper-rmsd-hist.py for all temperatures
• paper-parameters.py: Plot all parameters as function of temperature, default in Eyring plot; optional argument --normal to plot it in 'linear scale'
• paper-ss-tau.py: Plot steady states and time constants as function of voltage for all temperatures
• paper-eyring-q10-fit.py: Plot all parameters as function of temperature with fits of Generalised Eyring and Q10 relationships, default in Eyring plot; optional argument --normal to plot it in 'linear scale'
• paper-fitting-and-validation-eyring-q10-v2.py: paper-fitting-and-validation-eyring-q10.py version 2
• paper-eyring-q10-ss-tau.py: Same as paper-parameters.py with addition of Generalised Eyring and Q10 relationships results; require results from paper-eyring-q10-fit.py
• paper-normalisation-demo.py: Plot demo of the 'maximum conductance value' estimation for normalisation purpose

Reproducing literature

• Zhou-1998-*: Try reproducing Zhou et al. 1998 results
• zhou-et-al-1998: Zhou et al. 1998 data
• Vandenberg-2006-*: Try reproducing Vandenberg et al. 2006 results
• vandenberg-et-al-2006: Vandenberg et al. 2006 data
• Mauerhofer-2016-*: Try reproducing Mauerhofer et al. 2016 results
• mauerhofer-et-al-2016: Mauerhofer et al. 2016 data

Other plots (simple plots for testing; results not used in publication)

• fit-multiple.py: Simple fitting for multiple selected cells, for testing mainly
• fit-fromqc.py: Fitting for all cells selected from QC; prefer fit.py and fit.sh
• plot-parameters-against-temperature-single-cell.py: Quick plot for multiple selected cells, for testing mainly
• plot-parameters-against-temperature.py: Quick plot for all fitted cells in out
• quick-plot-*: Random quick testing plots
• compare-normalisation-methods.py: Compare normalisation with 1. fitted conductance value and 2. extrapolation back to the step time at -120 mV step
• paper-fitting-and-validation-recordings.py: Plot all selected cells data (both fitting and validation) for room and body temperatures
• paper-fitting-and-validation-eyring-q10.py: Plot predictions of HBM, Generalised Eyring, and Q10 against data in fan charts; require argument protocol-id; require results from paper-eyring-q10-fit.py
• paper-fitting-and-validation-eyring-q102-v2.py: paper-fitting-and-validation-eyring-q10-v2.py with Q10 model extrapolate 'down' from body temperature, instead of usual Q10 model which extrapolate 'up' from room temperature