Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments

Understanding how gene expression programs are controlled requires identifying regulatory relationships between transcription factors and target genes. Gene regulatory networks are typically constructed from gene expression data acquired following genetic perturbation or environmental stimulus. Sing...

Full description

Bibliographic Details
Main Authors: Christopher A Jackson, Dayanne M Castro, Giuseppe-Antonio Saldi, Richard Bonneau, David Gresham
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-01-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/51254
_version_ 1818019860821573632
author Christopher A Jackson
Dayanne M Castro
Giuseppe-Antonio Saldi
Richard Bonneau
David Gresham
author_facet Christopher A Jackson
Dayanne M Castro
Giuseppe-Antonio Saldi
Richard Bonneau
David Gresham
author_sort Christopher A Jackson
collection DOAJ
description Understanding how gene expression programs are controlled requires identifying regulatory relationships between transcription factors and target genes. Gene regulatory networks are typically constructed from gene expression data acquired following genetic perturbation or environmental stimulus. Single-cell RNA sequencing (scRNAseq) captures the gene expression state of thousands of individual cells in a single experiment, offering advantages in combinatorial experimental design, large numbers of independent measurements, and accessing the interaction between the cell cycle and environmental responses that is hidden by population-level analysis of gene expression. To leverage these advantages, we developed a method for scRNAseq in budding yeast (Saccharomyces cerevisiae). We pooled diverse transcriptionally barcoded gene deletion mutants in 11 different environmental conditions and determined their expression state by sequencing 38,285 individual cells. We benchmarked a framework for learning gene regulatory networks from scRNAseq data that incorporates multitask learning and constructed a global gene regulatory network comprising 12,228 interactions.
first_indexed 2024-04-14T07:57:18Z
format Article
id doaj.art-21850d8c56ad4b6cb1b3e482f06ce76e
institution Directory Open Access Journal
issn 2050-084X
language English
last_indexed 2024-04-14T07:57:18Z
publishDate 2020-01-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj.art-21850d8c56ad4b6cb1b3e482f06ce76e2022-12-22T02:04:59ZengeLife Sciences Publications LtdeLife2050-084X2020-01-01910.7554/eLife.51254Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environmentsChristopher A Jackson0https://orcid.org/0000-0002-8769-2710Dayanne M Castro1Giuseppe-Antonio Saldi2Richard Bonneau3https://orcid.org/0000-0003-4354-7906David Gresham4https://orcid.org/0000-0002-4028-0364Center For Genomics and Systems Biology, New York University, New York, United States; Department of Biology, New York University, New York, United StatesDepartment of Biology, New York University, New York, United StatesDepartment of Biology, New York University, New York, United StatesCenter For Genomics and Systems Biology, New York University, New York, United States; Department of Biology, New York University, New York, United States; Courant Institute of Mathematical Sciences, Computer Science Department, New York University, New York, United States; Center For Data Science, New York University, New York, United States; Flatiron Institute, Center for Computational Biology, Simons Foundation, New York, United StatesCenter For Genomics and Systems Biology, New York University, New York, United States; Department of Biology, New York University, New York, United StatesUnderstanding how gene expression programs are controlled requires identifying regulatory relationships between transcription factors and target genes. Gene regulatory networks are typically constructed from gene expression data acquired following genetic perturbation or environmental stimulus. Single-cell RNA sequencing (scRNAseq) captures the gene expression state of thousands of individual cells in a single experiment, offering advantages in combinatorial experimental design, large numbers of independent measurements, and accessing the interaction between the cell cycle and environmental responses that is hidden by population-level analysis of gene expression. To leverage these advantages, we developed a method for scRNAseq in budding yeast (Saccharomyces cerevisiae). We pooled diverse transcriptionally barcoded gene deletion mutants in 11 different environmental conditions and determined their expression state by sequencing 38,285 individual cells. We benchmarked a framework for learning gene regulatory networks from scRNAseq data that incorporates multitask learning and constructed a global gene regulatory network comprising 12,228 interactions.https://elifesciences.org/articles/51254single cell RNA sequencinggene regulatory networkstranscription factors
spellingShingle Christopher A Jackson
Dayanne M Castro
Giuseppe-Antonio Saldi
Richard Bonneau
David Gresham
Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments
eLife
single cell RNA sequencing
gene regulatory networks
transcription factors
title Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments
title_full Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments
title_fullStr Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments
title_full_unstemmed Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments
title_short Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments
title_sort gene regulatory network reconstruction using single cell rna sequencing of barcoded genotypes in diverse environments
topic single cell RNA sequencing
gene regulatory networks
transcription factors
url https://elifesciences.org/articles/51254
work_keys_str_mv AT christopherajackson generegulatorynetworkreconstructionusingsinglecellrnasequencingofbarcodedgenotypesindiverseenvironments
AT dayannemcastro generegulatorynetworkreconstructionusingsinglecellrnasequencingofbarcodedgenotypesindiverseenvironments
AT giuseppeantoniosaldi generegulatorynetworkreconstructionusingsinglecellrnasequencingofbarcodedgenotypesindiverseenvironments
AT richardbonneau generegulatorynetworkreconstructionusingsinglecellrnasequencingofbarcodedgenotypesindiverseenvironments
AT davidgresham generegulatorynetworkreconstructionusingsinglecellrnasequencingofbarcodedgenotypesindiverseenvironments