基于梯度的参数优化方法开发的hiPSC-CMs的细胞特异模型适应了两个不同的动力电位波形
Yixin Zhang1, Futoshi Toyoda2,3, Yukiko Himeno4,5
1Graduate School of Life Sciences, Ritsumeikan University, Kusatsu, Japan.
Scientific reports
|June 7, 2024
概括
在分析控制和阻塞波形时,参数优化成功识别了心脏动作潜在的离子电流. 这种方法应用于人类诱导的多能干细胞衍生的心肌细胞,即使在有噪音的数据中也被证明是可靠的.
科学领域:
- 心血管生理学心血管生理学
- 计算生物学 计算生物学
- 生物物理学的生物物理.
背景情况:
- 参数优化 (PO) 方法用于使用计算模型确定心动电位 (AP) 波形中的离子电流组成.
- 由于有限的信息,在PO方法中安装单个AP记录可能不足以提供独特的解决方案.
研究的目的:
- 提高PO方法的准确性和可靠性,用于剖析心脏离子电流组成.
- 用人类诱导多能干细胞衍生心肌细胞 (hiPSC-CMs) 的实验数据验证PO方法.
主要方法:
- 用心膜激发的计算模型进行初始PO方法测试.
- 将PO应用于一对控制和在中IKr阻断的AP波形.
- 在来自hiPSC-CMs的实验AP记录上测试了PO方法,包括控制状态和IKr-blocked状态.
- 实现了稳定的细分选择和代处理,以克服实验数据的挑战.
主要成果:
- 当应用到in silico控制和单通道阻塞AP对时,PO方法表现出了完美的性能.
- 从hiPSC-CMs同时安装实验控制器和IKr-blocked APs最初是具有挑战性的,因为信号噪声和可变性.
- 选择稳定的记录段和采用代PO处理在很大程度上解决了技术问题.
- 从优化参数得出的定量离子机制与已建立的生理学理解保持一致.
结论:
- PO方法对于确定心脏离子电流组成非常有效,特别是在分析配对控制和阻塞AP波形时.
- 具有稳定的细分选择的代PO增强了分析来自hiPSC-CMs的实验AP数据的稳定性.
- 经过验证的PO方法为心脏电生理学提供了可靠的定量见解,与现有知识相一致.
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