PT - JOURNAL ARTICLE AU - Xiaojun Ma AU - Ashwin Somasundaram AU - Zengbiao Qi AU - Harinder Singh AU - Hatice Ulku Osmanbeyoglu TI - SPaRTAN, a computational framework for linking cell-surface receptors to transcriptional regulators AID - 10.1101/2020.12.22.423961 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.12.22.423961 4099 - http://biorxiv.org/content/early/2020/12/22/2020.12.22.423961.short 4100 - http://biorxiv.org/content/early/2020/12/22/2020.12.22.423961.full AB - 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.Competing Interest StatementThe authors have declared no competing interest.