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Abstract

Spike sorting is a critical first step in extracting neural signals from large-scale multi-electrode array (MEA) data. This manuscript presents several new techniques that make MEA spike sorting more robust and accurate. Our pipeline is based on an efficient multi-stage "triage-then-cluster-then-pursuit" approach that initially extracts only clean, high-quality waveforms from the electrophysiological time series by temporarily skipping noisy or "collided" events (representing two neurons firing synchronously). This is accomplished by developing a neural network detection and denoising method followed by efficient outlier triaging. The denoised spike waveforms are then used to infer the set of spike templates through nonparametric Bayesian clustering. We use a divide-and-conquer strategy to parallelize this clustering step. Finally, we recover collided waveforms with matching-pursuit deconvolution techniques, and perform further split-and-merge steps to estimate additional templates from the pool of recovered waveforms. We apply the new pipeline to data recorded in the primate retina, where high firing rates and highly-overlapping axonal units provide a challenging testbed for the deconvolution approach; in addition, the well-defined mosaic structure of receptive fields in this preparation provides a useful quality check on any spike sorting pipeline. We show that our pipeline improves on the state-of-the-art in spike sorting (and outperforms manual sorting) on both real and semi-simulated MEA data with > 500 electrodes; open source code can be found at https://github.com/paninski-lab/yass.

Abstract summary

Claude Opus 5.5 · xhigh effort · 2 Nov 2026 · from the abstract

YASS sorts spikes from multi-electrode arrays with > 500 electrodes using neural network detection and denoising, parallelized nonparametric Bayesian clustering, and matching-pursuit deconvolution, outperforming manual sorting on primate retina recordings.

Extracting single-neuron signals from large-scale multi-electrode array (MEA) recordings is challenging when firing rates are high, axonal units overlap, and synchronous spikes collide. YASS introduces a multi-stage triage-then-cluster-then-pursuit pipeline that defers noisy or collided waveforms during initial template inference and recovers them afterward via matching-pursuit deconvolution.

Key results

  1. SuggestedYASS improves upon existing spike sorting methods and outperforms manual spike sorting on both real and semi-simulated primate retina multi-electrode array recordings.

    Evaluated on real and semi-simulated primate retina MEA recordings with > 500 electrodes using receptive field mosaic structure as a quality check (numerical accuracy metrics are not stated in the abstract). · Abstract

Methods, data and reproducibility

YASS uses a neural network to detect and denoise spike waveforms, triages out noisy or synchronously collided two-neuron events, infers spike templates via divide-and-conquer parallelized nonparametric Bayesian clustering, and resolves collided spikes through matching-pursuit deconvolution followed by iterative template split-and-merge steps.

  • Real and semi-simulated large-scale multi-electrode array recordings from retina · non-human primate · n = > 500 electrodes
Methods & tools
YASS
Reproducibility gaps
Code is open source on GitHub, but no links or accessions are provided for the real or semi-simulated primate retina MEA datasets.
Limitations (1)
  • The abstract does not report quantitative accuracy metrics, runtime benchmarks, or names of the baseline spike sorters compared against YASS. · noted in this summary

Read this if you sort spikes from dense multi-electrode array recordings with overlapping units and high synchronous firing rates.

Citations
63

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