Cell type matching across species using protein embeddings and transfer learning

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Motivation Knowing the relation between cell types is crucial for translating experimental results from mice to humans. Establishing cell type matches, however, is hindered by the biological differences between the species. A substantial amount of evolutionary information between genes that could be used to align the species is discarded by most of the current methods since they only use one-to-one orthologous genes. Some methods try to retain the information by explicitly including the relation between genes, however, not without caveats. Results In this work, we present a model to Transfer and Align Cell Types in Cross-Species analysis (TACTiCS). First, TACTiCS uses a natural language processing model to match genes using their protein sequences. Next, TACTiCS employs a neural network to classify cell types within a species. Afterwards, TACTiCS uses transfer learning to propagate cell type labels between species. We applied TACTiCS on scRNA-seq data of the primary motor cortex of human, mouse and marmoset. Our model can accurately match and align cell types on these datasets. Moreover, at a high resolution, our model outperforms the state-of-the-art method SAMap. Finally, we show that our gene matching method results in better matches than BLAST, both in our model and SAMap. Availability https://github.com/kbiharie/TACTiCS Contact a.mahfouz@lumc.nl

Authors 4

1. Kirti Biharie Aachen Department of Human Genetics Leiden Computational Biology Center

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Delft Bioinformatics Lab, Delft University of Technology, Van Mourik Broekmanweg 6, 2628XE, Delft, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Einthovenweg 0, 333ZC, Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, Einthovenweg 20, 2ZC, Leiden, The Netherlands

2. Lieke Michielsen Aachen Department of Human Genetics Leiden Computational Biology Center

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Delft Bioinformatics Lab, Delft University of Technology, Van Mourik Broekmanweg 6, 2628XE, Delft, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Einthovenweg 0, 333ZC, Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, Einthovenweg 20, 2ZC, Leiden, The Netherlands

3. Marcel J. T. Reinders Aachen Department of Human Genetics Leiden Computational Biology Center

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Delft Bioinformatics Lab, Delft University of Technology, Van Mourik Broekmanweg 6, 2628XE, Delft, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Einthovenweg 0, 333ZC, Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, Einthovenweg 20, 2ZC, Leiden, The Netherlands

4. Ahmed Essam Mahfouz corresponding Aachen Department of Human Genetics Leiden Computational Biology Center

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Delft Bioinformatics Lab, Delft University of Technology, Van Mourik Broekmanweg 6, 2628XE, Delft, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Einthovenweg 0, 333ZC, Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, Einthovenweg 20, 2ZC, Leiden, The Netherlands