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2016 ; 2
(4
): 239-250
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Low Dimensionality in Gene Expression Data Enables the Accurate Extraction of
Transcriptional Programs from Shallow Sequencing
#MMPMID27135536
Heimberg G
; Bhatnagar R
; El-Samad H
; Thomson M
Cell Syst
2016[Apr]; 2
(4
): 239-250
PMID27135536
show ga
A tradeoff between precision and throughput constrains all biological
measurements, including sequencing-based technologies. Here, we develop a
mathematical framework that defines this tradeoff between mRNA-sequencing depth
and error in the extraction of biological information. We find that
transcriptional programs can be reproducibly identified at 1% of conventional
read depths. We demonstrate that this resilience to noise of "shallow" sequencing
derives from a natural property, low dimensionality, which is a fundamental
feature of gene expression data. Accordingly, our conclusions hold for ?350
single-cell and bulk gene expression datasets across yeast, mouse, and human. In
total, our approach provides quantitative guidelines for the choice of sequencing
depth necessary to achieve a desired level of analytical resolution. We codify
these guidelines in an open-source read depth calculator. This work demonstrates
that the structure inherent in biological networks can be productively exploited
to increase measurement throughput, an idea that is now common in many branches
of science, such as image processing.