Back

Monod: mechanistic analysis of single-cell RNA sequencing count data

Gorin, G.; Pachter, L.

2022-06-12 bioinformatics
10.1101/2022.06.11.495771 bioRxiv
Show abstract

Single-cell RNA sequencing analysis centers on illuminating cell diversity and understanding the transcriptional mechanisms underlying cellular function. These datasets are large, noisy, and complex. Current analyses prioritize noise removal and dimensionality reduction to tackle these challenges and extract biological insight. We propose an alternative, physical approach to leverage the stochasticity, size, and multimodal nature of these data to explicitly distinguish their biological and technical facets while revealing the underlying regulatory processes. With the Python package Monod, we demonstrate how nascent and mature RNA counts, present in most published datasets, can be meaningfully "integrated" under biophysical models of transcription. By utilizing variation in these modalities, we can identify transcriptional modulation not discernible though changes in average gene expression, quantitatively compare mechanistic hypotheses of gene regulation, analyze transcriptional data from different technologies within a common framework, and minimize the use of opaque or distortive normalization and transformation techniques.

Matching journals

The top 3 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.