Random matrix theory as a tool for analysing biological data

The sinoatrial node (SAN) is the pacemaker region of the heart.
Recently calcium signals, believed to be crucially important in heart
rhythm generation, have been imaged in intact SAN and shown to be
heterogeneous in various regions of the SAN. However, calcium imaging
is noisy, and the calcium signal heterogeneity has not been
mathematically analyzed to distinguish meaningful signals from
randomness or to identify signalling regions in an objective way. In
this work we apply methods of random matrix theory (RMT) developed for
financial data and used for analysis of various biological data sets
including β-cell collectives and EEG data. We find eigenvalues of the
correlation matrix that deviate from RMT predictions, and thus are not
explained by randomness but carry additional meaning. We use
localization properties of the eigenvectors corresponding to high
eigenvalues to locate particular signalling modules. We find that the
top eigenvector captures a common response of the SAN to action
potential. In some cases, the eigenvector corresponding to the second
highest eigenvalue appears to yield a possible pacemaker region as its
calcium signals predate the action potential. Next we study the
relationship between covariance coefficients and distance and find
that there are long range correlations, indicating intercellular
interactions in most cases. Lastly, we perform an analysis of nearest
neighbor eigenvalue distances and find that it coincides with the
universal Wigner surmise. On the other hand, the number variance,
which captures eigenvalue correlations, is a parameter that is
sensitive to experimental conditions. Thus RMT application to SAN
allows to remove noise and the global effects of the action potential
and thereby isolate the correlations in calcium signalling which are
local. This talk is based on joint work with Chloe Norris with a
preprint found here:
https://www.biorxiv.org/content/10.1101/2022.02.25.482007v1.