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bioRxiv · 10.64898/2026.04.10.717770

MIMIQ: Fast mutual information calculation and significance testing for single-cell RNA sequencing analysis

O'Hanlon, D.·Garcia Busto, S.·Perez Carrasco, R.
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Abstract

Mutual information is a fundamental quantity in information theory that describes the non-linear dependency between two variables, and has numerous applications within bioinformatics and beyond. However, its exploitation is hampered by a trade-off between computational intensity and accuracy. Here we present an adaptive binning approach to computing the pairwise mutual information, optimized for small integer counts such as those observed in single-cell RNA sequencing. By assuming a sampling distribution such as the negative binomial, a {chi}2 test statistic for hypothesis testing can be computed simultaneously via a copula transformation. Using these quantities, we show how gene rewiring of CD4+ naive T-cells during SARS-CoV-2 infection can be studied using a single-cell sequencing dataset of healthy and COVID-19 donors.

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O'Hanlon, D., Garcia Busto, S., Perez Carrasco, R.. 2026-04-13. MIMIQ: Fast mutual information calculation and significance testing for single-cell RNA sequencing analysis. https://doi.org/10.64898/2026.04.10.717770

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