The Escherichia coli transcriptome mostly consists of independently regulated modules

Sastry, Anand V.; Gao, Ye; Szubin, Richard; Hefner, Ying; Xu, Sibei; Kim, Donghyuk; Choudhary, Kumari Sonal; Yang, Laurence; King, Zachary A.; Palsson, Bernhard O.

doi:10.1038/s41467-019-13483-w

The Escherichia coli transcriptome mostly consists of independently regulated modules

Journal Article · Wed Dec 04 00:00:00 EST 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-13483-w· OSTI ID:1624220

^[1]; Gao, Ye ^[2]; Szubin, Richard ^[2]; Hefner, Ying ^[2]; ^[2]; Kim, Donghyuk ^[2]; ^[2]; Yang, Laurence ^[2]; ^[2]; ^[3]

Univ. of California San Diego, La Jolla, CA (United States); DOE/OSTI
Univ. of California San Diego, La Jolla, CA (United States)
Univ. of California San Diego, La Jolla, CA (United States); Novo Nordisk Foundation Center for Biosustainability, Lyngby (Denmark)

Underlying cellular responses is a transcriptional regulatory network (TRN) that modulates gene expression. A useful description of the TRN would decompose the transcriptome into targeted effects of individual transcriptional regulators. Here, we apply unsupervised machine learning to a diverse compendium of over 250 high-quality Escherichia coli RNA-seq datasets to identify 92 statistically independent signals that modulate the expression of specific gene sets. We show that 61 of these transcriptomic signals represent the effects of currently characterized transcriptional regulators. Condition-specific activation of signals is validated by exposure of E. coli to new environmental conditions. The resulting decomposition of the transcriptome provides: a mechanistic, systems-level, network-based explanation of responses to environmental and genetic perturbations; a guide to gene and regulator function discovery; and a basis for characterizing transcriptomic differences in multiple strains. Taken together, our results show that signal summation describes the composition of a model prokaryotic transcriptome.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)

Sponsoring Organization:: Novo Nordisk Foundation Center for Biosustainability; USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1624220

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
bacterial systems biology
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gene regulatory networks
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The Escherichia coli transcriptome mostly consists of independently regulated modules

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