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Accurate and robust inference of microbial growth dynamics from metagenomic sequencing

Tyler A. Joseph, Philippe Chlenski, Tal Korem, Itsik Pe’er
doi: https://doi.org/10.1101/2021.02.02.429365
Tyler A. Joseph
1Department of Computer Science, Columbia University, New York, NY, USA
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Philippe Chlenski
1Department of Computer Science, Columbia University, New York, NY, USA
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Tal Korem
2Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA
3Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, USA
4CIFAR Azrieli Global Scholars Program, CIFAR, Toronto, Ontario, Canada
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  • For correspondence: tk2829@cumc.columbia.edu itsik@cs.columbia.edu
Itsik Pe’er
1Department of Computer Science, Columbia University, New York, NY, USA
2Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA
5Data Science Institute, Columbia University, New York, NY, USA
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  • For correspondence: tk2829@cumc.columbia.edu itsik@cs.columbia.edu
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Abstract

Patterns of sequencing coverage along a bacterial genome—summarized by a peak-to-trough ratio (PTR)—have been shown to accurately reflect microbial growth rates, revealing a new facet of microbial dynamics and host-microbe interactions. Here, we introduce CoPTR (Compute PTR): a tool for computing PTRs from complete reference genomes and assemblies. We show that CoPTR is more accurate than the current state-of-the-art, while also providing more PTR estimates overall. We further develop theory formalizing a biological interpretation for PTRs. Using a reference database of 2935 species, we applied CoPTR to a case-control study of 1304 metagenomic samples from 106 individuals with irritable bowel disease. We show that PTRs have high inter-individual variation, are only loosely correlated with relative abundances, and are associated with disease status. We conclude by demonstrating how PTRs can be combined with relative abundances and metabolomics to investigate their effect on the microbiome.

Availability CoPTR is available from https://github.com/tyjo/coptr, with documentation on https://coptr.readthedocs.io.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 02, 2021.
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Accurate and robust inference of microbial growth dynamics from metagenomic sequencing
Tyler A. Joseph, Philippe Chlenski, Tal Korem, Itsik Pe’er
bioRxiv 2021.02.02.429365; doi: https://doi.org/10.1101/2021.02.02.429365
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Accurate and robust inference of microbial growth dynamics from metagenomic sequencing
Tyler A. Joseph, Philippe Chlenski, Tal Korem, Itsik Pe’er
bioRxiv 2021.02.02.429365; doi: https://doi.org/10.1101/2021.02.02.429365

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