FRAME-C: A knowledge-augmented deep learning pipeline for classifying multi-electrode array electrophysiological signals

TL;DR

FRAME-C is a knowledge-augmented deep learning pipeline that combines domain knowledge and raw electrophysiological data to classify signals and identify ALS-specific neural phenotypes with improved accuracy.

Contribution

It introduces a novel pipeline that integrates handcrafted features with deep learning for MEA data analysis, enhancing classification performance and interpretability.

Findings

Over 11% performance improvement on real MEA data

Up to 25% improvement on simulated data

Provides insights into ALS-related neural features

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motor neuron degeneration, with alterations in neural excitability serving as key indicators. Recent advancements in induced pluripotent stem cell (iPSC) technology have enabled the generation of human iPSC-derived neuronal cultures, which, when combined with multi-electrode array (MEA) electrophysiology, provide rich spatial and temporal electrophysiological data. Traditionally, MEA data is analyzed using handcrafted features based on potentially imperfect domain knowledge, which while useful may not fully capture all useful characteristics inherent in the data. Machine learning, particularly deep learning, has the potential to automatically learn relevant characteristics from raw data without solely relying on handcrafted feature extraction. However, handcrafted features remain critical for encoding domain knowledge and improving interpretability, especially with limited or noisy data. This study introduces FRAME-C, a knowledge-augmented machine learning pipeline that combines domain knowledge, raw spike waveform data, and deep learning techniques to classify MEA signals and identify ALS-specific phenotypes. FRAME-C leverages deep learning to learn important features from spike waveforms while incorporating handcrafted features such as spike amplitude, inter-spike interval, and spike duration, preserving key spatial and temporal information. We validate FRAME-C on both simulated and real MEA data from human iPSC-derived neuronal cultures, demonstrating superior performance over existing classification methods. FRAME-C shows over 11% improvement on real data and up to 25% on simulated data. We also show FRAME-C can evaluate handcrafted feature importance, providing insights into ALS phenotypes.