Genetic and environmental perturbations lead to regulatory decoherence
Amanda J Lea,
Olli T. Raitakari,
Noah A. Zaitlen,
Julien F. Ayroles
Posted 14 Jul 2018
bioRxiv DOI: 10.1101/369306 (published DOI: 10.7554/elife.40538)
Posted 14 Jul 2018
Correlation among traits is a fundamental feature of biological systems. From morphological characters, to transcriptional or metabolic networks, the correlations we routinely observe between traits reflect a shared regulation that remains poorly understood and difficult to study. To address this problem, we developed a new and flexible approach that allows us to identify factors associated with variation in correlation between individuals. Here, we use data from three large human cohorts to study the effects of genetic variation and environmental perturbation on correlations among mRNA transcripts and among NMR metabolites. We first show that environmental exposures (namely, infection and disease) lead to a systematic loss of correlation, which we define as 'decoherence'. Using longitudinal data, we show that decoherent metabolites are better predictors of whether someone will develop metabolic syndrome than metabolites commonly used as biomarkers of this disease. Finally, we show that correlation itself is a trait under genetic control: specifically, we mapped and replicated hundreds of 'correlation QTLs', which often involve transcription factors or their known target genes. Together, this work furthers our understanding of how and why coordinated biological processes break down, and highlights the role of decoherence in disease emergence.
- Downloaded 737 times
- Download rankings, all-time:
- Site-wide: 30,342
- In genomics: 2,763
- Year to date:
- Site-wide: 113,872
- Since beginning of last month:
- Site-wide: 96,799
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!