Cross-species imputation and comparison of single-cell transcriptomic profiles
Ran Zhang1,2, Mu Yang3, Jacob Schreiber4
1Department of Genome Sciences, University of Washington.
Biorxiv : the Preprint Server for Biology
|October 31, 2023
Summary
Icebear, a new neural network, predicts gene expression across species. This framework aids cross-species cell comparisons and reveals evolutionary adaptations in gene regulation.
Area of Science:
- Genomics
- Evolutionary Biology
- Computational Biology
Background:
- Cross-species gene expression analysis is crucial for understanding evolution and transferring knowledge from model organisms to humans.
- Single-cell RNA sequencing (scRNA-seq) offers high resolution but faces challenges in cross-species comparisons due to data sparsity, batch effects, and cell matching issues.
- Obtaining single-cell profiles can be difficult in certain biological contexts, limiting research scope.
Purpose of the Study:
- To develop a computational framework for accurate cross-species prediction and comparison of single-cell gene expression profiles.
- To address limitations in current scRNA-seq cross-species analysis, including data sparsity and batch effects.
- To enable high-resolution cell type and disease profiling in under-characterized species and contexts.
Main Methods:
- Developed Icebear, a neural network framework that decomposes single-cell measurements into distinct factors (cell identity, species, batch).
- Utilized Icebear to predict single-cell gene expression profiles across different species.
- Applied Icebear to compare conserved gene expression patterns between mammals and chickens, focusing on sex chromosome evolution.
Main Results:
- Icebear accurately predicts single-cell gene expression profiles across species.
- The framework provides high-resolution cell type and disease profiles, even in challenging biological contexts.
- Direct cross-species comparison revealed novel insights into the evolutionary adaptations of X-chromosome gene regulation in mammals.
Conclusions:
- Icebear is an effective tool for cross-species single-cell gene expression analysis and prediction.
- The study provides a new method to overcome common challenges in comparative scRNA-seq studies.
- This research offers the first direct comparison of X-chromosome gene expression evolution across mammals and chickens, uncovering diverse adaptations.


