Linking Expression of Cell-Surface Receptors with Transcription Factors by Computational Analysis of Paired Single-Cell Proteomes and Transcriptomes
Complex signaling and transcriptional programs control the development and physiology of specialized cell types. Genetic perturbations in these programs cause human cancers to arise from a diverse set of specialized cell types and developmental states. Understanding these complex systems and their p...
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| Veröffentlicht in: | Methods in molecular biology (Clifton, N.J.) Jg. 2660; S. 149 |
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2023
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| Abstract | Complex signaling and transcriptional programs control the development and physiology of specialized cell types. Genetic perturbations in these programs cause human cancers to arise from a diverse set of specialized cell types and developmental states. Understanding these complex systems and their potential to drive cancer is critical for the development of immunotherapies and druggable targets. Pioneering single-cell multi-omics technologies that analyze transcriptional states have been coupled with the expression of cell-surface receptors. This chapter describes SPaRTAN (Single-cell Proteomic and RNA-based Transcription factor Activity Network), a computational framework, to link transcription factors with cell-surface protein expression. SPaRTAN uses CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) data and cis-regulatory sites to model the effect of interactions between transcription factors and cell-surface receptors on gene expression. We demonstrate the pipeline for SPaRTAN using CITE-seq data from peripheral blood mononuclear cells. |
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| AbstractList | Complex signaling and transcriptional programs control the development and physiology of specialized cell types. Genetic perturbations in these programs cause human cancers to arise from a diverse set of specialized cell types and developmental states. Understanding these complex systems and their potential to drive cancer is critical for the development of immunotherapies and druggable targets. Pioneering single-cell multi-omics technologies that analyze transcriptional states have been coupled with the expression of cell-surface receptors. This chapter describes SPaRTAN (Single-cell Proteomic and RNA-based Transcription factor Activity Network), a computational framework, to link transcription factors with cell-surface protein expression. SPaRTAN uses CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) data and cis-regulatory sites to model the effect of interactions between transcription factors and cell-surface receptors on gene expression. We demonstrate the pipeline for SPaRTAN using CITE-seq data from peripheral blood mononuclear cells. Complex signaling and transcriptional programs control the development and physiology of specialized cell types. Genetic perturbations in these programs cause human cancers to arise from a diverse set of specialized cell types and developmental states. Understanding these complex systems and their potential to drive cancer is critical for the development of immunotherapies and druggable targets. Pioneering single-cell multi-omics technologies that analyze transcriptional states have been coupled with the expression of cell-surface receptors. This chapter describes SPaRTAN (Single-cell Proteomic and RNA-based Transcription factor Activity Network), a computational framework, to link transcription factors with cell-surface protein expression. SPaRTAN uses CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) data and cis-regulatory sites to model the effect of interactions between transcription factors and cell-surface receptors on gene expression. We demonstrate the pipeline for SPaRTAN using CITE-seq data from peripheral blood mononuclear cells.Complex signaling and transcriptional programs control the development and physiology of specialized cell types. Genetic perturbations in these programs cause human cancers to arise from a diverse set of specialized cell types and developmental states. Understanding these complex systems and their potential to drive cancer is critical for the development of immunotherapies and druggable targets. Pioneering single-cell multi-omics technologies that analyze transcriptional states have been coupled with the expression of cell-surface receptors. This chapter describes SPaRTAN (Single-cell Proteomic and RNA-based Transcription factor Activity Network), a computational framework, to link transcription factors with cell-surface protein expression. SPaRTAN uses CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) data and cis-regulatory sites to model the effect of interactions between transcription factors and cell-surface receptors on gene expression. We demonstrate the pipeline for SPaRTAN using CITE-seq data from peripheral blood mononuclear cells. |
| Author | Osmanbeyoglu, Hatice Ulku Sagan, April Ma, Xiaojun Ramjattun, Koushul |
| Author_xml | – sequence: 1 givenname: April surname: Sagan fullname: Sagan, April organization: UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA – sequence: 2 givenname: Xiaojun surname: Ma fullname: Ma, Xiaojun organization: UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA – sequence: 3 givenname: Koushul surname: Ramjattun fullname: Ramjattun, Koushul organization: UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA – sequence: 4 givenname: Hatice Ulku surname: Osmanbeyoglu fullname: Osmanbeyoglu, Hatice Ulku email: osmanbeyogluhu@pitt.edu, osmanbeyogluhu@pitt.edu, osmanbeyogluhu@pitt.edu, osmanbeyogluhu@pitt.edu organization: Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA. osmanbeyogluhu@pitt.edu |
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| Keywords | Droplet-based scRNA-seq scVerse and Scanpy ecosystems Affinity regression (AR) scADT-seq Jupyter notebook pySPaRTAN package DoRothEA database Single-cell Proteomic and RNA-based Transcription factor Activity Network (SPaRTAN) Python package Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) Antibody-derived tags (ADTs) |
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| SubjectTerms | Humans Leukocytes, Mononuclear Proteome Proteomics Single-Cell Analysis Transcription Factors - genetics Transcriptome |
| Title | Linking Expression of Cell-Surface Receptors with Transcription Factors by Computational Analysis of Paired Single-Cell Proteomes and Transcriptomes |
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