Back

Inferring absolute counts from proportions by constraining multivariate normal distributions

Hage, J.; Koestler, D.; Christensen, B.

2025-11-05 systems biology
10.1101/2025.11.04.686543 bioRxiv
Show abstract

Biological measurements often result in proportional data, which derive from underlying biological counts. Proportion data are lacking a dimension of information as compared to counts, restricting available analysis methods and separating the data from the biology. We demonstrate a mathematical technique that estimates absolute counts corresponding to proportion data, which we refer to as Mahalanobis Count Inference (MCI). MCI uses information from a population-representative multivariate normal (MVN) distribution of component counts and ultimately outputs an estimated count and a confidence interval per observation proportion vector. We apply MCI to the imputation of white blood cell (WBC) counts, and of total mRNA within single cells. The method performs very well on total mRNA recapitulation (log-space Pearsons R = 0.81), and well enough on WBC counts to outperform proportions at multiple classification tasks. MCI operates with minimal assumptions, and is applicable to many compositional omics.

Published in npj Systems Biology and Applications (predicted rank #5) · training set

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.