Prediction of single-cell gene expression for transcription factor analysis. Issue 11 (30th October 2020)

• Record Type: Journal Article
• Authors: Behjati Ardakani, Fatemeh; Kattler, Kathrin; Heinen, Tobias; Schmidt, Florian; Feuerborn, David; Gasparoni, Gilles; Lepikhov, Konstantin; Nell, Patrick; Hengstler, Jan; Walter, Jörn; Schulz, Marcel H
• Is Part Of: GigaScience. Volume 9:Issue 11(2020)
• Publication Date: 2020-10-30
• Subjects: Information storage and retrieval systems -- Research -- Periodicals; Biology -- Research -- Periodicals; Medical sciences -- Research -- Periodicals; Database management -- Periodicals; 570.285
• DOI: 10.1093/gigascience/giaa113
• Languages: English
• ISSNs: 2047-217X

Abstract

Abstract: Background: Single-cell RNA sequencing is a powerful technology to discover new cell types and study biological processes in complex biological samples. A current challenge is to predict transcription factor (TF) regulation from single-cell RNA data. Results: Here, we propose a novel approach for predicting gene expression at the single-cell level using cis -regulatory motifs, as well as epigenetic features. We designed a tree-guided multi-task learning framework that considers each cell as a task. Through this framework we were able to explain the single-cell gene expression values using either TF binding affinities or TF ChIP-seq data measured at specific genomic regions. TFs identified using these models could be validated by the literature. Conclusion: Our proposed method allows us to identify distinct TFs that show cell type–specific regulation. This approach is not limited to TFs but can use any type of data that can potentially be used in explaining gene expression at the single-cell level to study factors that drive differentiation or show abnormal regulation in disease. The implementation of our workflow can be accessed under an MIT license via https://github.com/SchulzLab/Triangulate .