ICAT: a novel algorithm to robustly identify cell states following perturbations in single-cell transcriptomes
Date
2023-05-04
Authors
Hawkins, Dakota Y.
Zuch, Daniel T.
Huth, James
Rodriguez-Sastre, Nahomie
McCutcheon, Kelley R.
Glick, Abigail
Lion, Alexandra T.
Thomas, Christopher F.
Descoteaux, Abigail E.
Johnson, William Evan
Version
Published version
OA Version
Citation
D.Y. Hawkins, D.T. Zuch, J. Huth, N. Rodriguez-Sastre, K.R. McCutcheon, A. Glick, A.T. Lion, C.F. Thomas, A.E. Descoteaux, W.E. Johnson, C.A. Bradham. 2023. "ICAT: a novel algorithm to robustly identify cell states following perturbations in single-cell transcriptomes." Bioinformatics, Volume 39, Issue 5, pp.btad278-. https://doi.org/10.1093/bioinformatics/btad278
Abstract
MOTIVATION: The detection of distinct cellular identities is central to the analysis of single-cell RNA sequencing (scRNA-seq) experiments. However, in perturbation experiments, current methods typically fail to correctly match cell states between conditions or erroneously remove population substructure. Here, we present the novel, unsupervised algorithm Identify Cell states Across Treatments (ICAT) that employs self-supervised feature weighting and control-guided clustering to accurately resolve cell states across heterogeneous conditions. RESULTS: Using simulated and real datasets, we show ICAT is superior in identifying and resolving cell states compared with current integration workflows. While requiring no a priori knowledge of extant cell states or discriminatory marker genes, ICAT is robust to low signal strength, high perturbation severity, and disparate cell type proportions. We empirically validate ICAT in a developmental model and find that only ICAT identifies a perturbation-unique cellular response. Taken together, our results demonstrate that ICAT offers a significant improvement in defining cellular responses to perturbation in scRNA-seq data. AVAILABILITY AND IMPLEMENTATION: https://github.com/BradhamLab/icat.
Description
License
VC The Author(s) 2023. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.