SPaRTAN, a computational framework for linking cell-surface receptors to transcriptional regulators
Xiaojun Ma, Ashwin Somasundaram, Zengbiao Qi, Douglas Hartman, Harinder Singh, Hatice Ulku Osmanbeyoglu
University of Pittsburgh & UPMC Hillman Cancer Center
doi: https://doi.org/10.1101/2020.12.22.423961
ABSTRACT
The developmental pathways and functions of specialized cell types are dependent on the complex interplay between signaling and transcriptional networks. We present SPaRTAN (Single-cell Proteomic and RNA based Transcription factor Activity Network), a computational method to link cell-surface receptors to transcription factors (TFs) by exploiting Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) datasets with cis-regulatory information. SPaRTAN is applied to peripheral blood mononuclear cells (PBMCs) to predict the coupling of signaling receptors with cell context-specific TF activities. The predictions are validated by flow cytometry analyses. SPaRTAN is then used to analyze the signaling coupled TF activity states of tumor infiltrating CD8+ T cells in malignant peritoneal and pleural mesotheliomas. SPaRTAN greatly enhances the utility of CITE-seq datasets to probe signaling coupled TF networks that regulate developmental or functional transitions in cellular states.
SPaRTAN INPUT MATRICIES
D Matricies - text (comma-delimited) table includes curated TF target-gene interaction. Rows represent genes. Columns represent TFs.
PMBC (All cell types)
Malignant Pleural Mesothelioma (CD8 T Cells)
Malignant Peritoneal Mesothelioma (CD8 T Cells)
P Matricies - text (comma-delimited) table includes cell-specific surface protein expression. Rows represent barcoded cells. Columns represent surface proteins based on the CITE-seq experiment.
PMBC 5k v3 Chemistry (B Cells)
PMBC 5k v3 Chemistry (CD4 Memory T Cells)
PMBC 5k v3 Chemistry (CD4 Naïve T Cells)
PMBC 5k v3 Chemistry (CD8 T Cells)
PMBC 5k v3 Chemistry (CD14+ Monocytes)
PMBC 5k v3 Chemistry (CD16+ Monocytes)
PMBC 5k v3 Chemistry (Dendritic Cells)
PMBC 5k v3 Chemistry (Natural Killer Cells)
PMBC 5k Next GEM (B Cells)
PMBC 5k Next GEM (CD4 Memory T Cells)
PMBC 5k Next GEM (CD4 Naïve T Cells)
PMBC 5k Next GEM (CD8 T Cells)
PMBC 5k Next GEM (CD14+ Monocytes)
PMBC 5k Next GEM (CD16+ Monocytes)
PMBC 5k Next GEM (Dendritic Cells)
PMBC 5k Next GEM (Natural Killer Cells)
Malignant Peritoneal Mesothelioma (CD8 T Cells)
Malignant Pleural Mesothelioma (CD8 T Cells)
Y Matricies - text (comma-delimited) table includes cell-specific gene expression. Rows represent genes. Columns represent barcoded cells.
PMBC 5k v3 Chemistry (B Cells)
PMBC 5k v3 Chemistry (CD4 Memory T Cells)
PMBC 5k v3 Chemistry (CD4 Naïve T Cells)
PMBC 5k v3 Chemistry (CD8 T Cells)
PMBC 5k v3 Chemistry (CD14+ Monocytes)
PMBC 5k v3 Chemistry (CD16+ Monocytes)
PMBC 5k v3 Chemistry (Dendritic Cells)
PMBC 5k v3 Chemistry (Natural Killer Cells)
PMBC 5k Next GEM (B Cells)
PMBC 5k Next GEM (CD4 Memory T Cells)
PMBC 5k Next GEM (CD4 Naïve T Cells)
PMBC 5k Next GEM (CD8 T Cells)
PMBC 5k Next GEM (CD14+ Monocytes)
PMBC 5k Next GEM (CD16+ Monocytes)
PMBC 5k Next GEM (Dendritic Cells)
PMBC 5k Next GEM (Natural Killer Cells)
Malignant Peritoneal Mesothelioma (CD8 T Cells)
Malignant Pleural Mesothelioma (CD8 T Cells)
SPaRTAN OUTPUT
Predicted Cell-Specific TF Activity Tables - Rows represent TFs. Columns represent barcoded cells.
PMBC 5k v3 Chemistry (B Cells)
PMBC 5k v3 Chemistry (CD4 Memory T Cells)
PMBC 5k v3 Chemistry (CD4 Naïve T Cells)
PMBC 5k v3 Chemistry (CD8 T Cells)
PMBC 5k v3 Chemistry (CD14+ Monocytes)
PMBC 5k v3 Chemistry (CD16+ Monocytes)
PMBC 5k v3 Chemistry (Dendritic Cells)
PMBC 5k v3 Chemistry (Natural Killer Cells)
PMBC 5k Next GEM (B Cells)
PMBC 5k Next GEM (CD4 Memory T Cells)
PMBC 5k Next GEM (CD4 Naïve T Cells)
PMBC 5k Next GEM (CD8 T Cells)
PMBC 5k Next GEM (CD14+ Monocytes)
PMBC 5k Next GEM (CD16+ Monocytes)
PMBC 5k Next GEM (Dendritic Cells)
PMBC 5k Next GEM (Natural Killer Cells)
Malignant Pleural Mesothelioma (CD8 T Cells)
Malignant Peritoneal Mesothelioma (CD8 T Cells)
Pearson Correlation Coefficients of Predicted TF Activites and Surface Protein Expression - Rows represent surface proteins based on the CITE-seq experiment. Columns represent TFs.
PMBC 5k v3 Chemistry (B Cells)
PMBC 5k v3 Chemistry (CD4 Memory T Cells)
PMBC 5k v3 Chemistry (CD4 Naïve T Cells)
PMBC 5k v3 Chemistry (CD8 T Cells)
PMBC 5k v3 Chemistry (CD14+ Monocytes)
PMBC 5k v3 Chemistry (CD16+ Monocytes)
PMBC 5k v3 Chemistry (Dendritic Cells)
PMBC 5k v3 Chemistry (Natural Killer Cells)
PMBC 5k Next GEM (B Cells)
PMBC 5k Next GEM (CD4 Memory T Cells)
PMBC 5k Next GEM (CD4 Naïve T Cells)
PMBC 5k Next GEM (CD8 T Cells)
PMBC 5k Next GEM (CD14+ Monocytes)
PMBC 5k Next GEM (CD16+ Monocytes)
PMBC 5k Next GEM (Dendritic Cells)
PMBC 5k Next GEM (Natural Killer Cells)
Malignant Pleural Mesothelioma (CD8 T Cells)
Malignant Peritoneal Mesothelioma (CD8 T Cells)