Abstract

ABSTRACTThe technological leap of DNA sequencing generated a tension between modern metagenomics and historical microbiology. We are forcibly harmonizing the output of a modern tool with centuries of experimental knowledge derived from culture-based microbiology. As a thought experiment, we borrow the notion of Cartesian doubt from philosopher Rene Descartes, who used doubt to build a philosophical framework from his incorrigible statement that “I think therefore I am.” We aim to cast away preconceived notions and conceptualize microorganisms through the lens of metagenomic sequencing alone. Specifically, we propose funding and building analysis and engineering methods that neither search for nor rely on the assumption of independent genomes bound by lipid barriers containing discrete functional roles and taxonomies. We propose that a view of microbial communities based in sequencing will engender novel insights into metagenomic structure and may capture functional biology not reflected within the current paradigm.

Highlights

  • The technological leap of DNA sequencing generated a tension between modern metagenomics and historical microbiology

  • Cartesian doubt—beginning with radical skepticism and moving forward with as few external assumptions as possible—can be used to reconceive our approaches to microbiome science, potentially avoiding biases and conflicts stemming from centuries of culture-based microbiology

  • We propose rethinking microbial communities as revealed via DNA sequencing, reimagining what microbial life may be instead of assuming what it is based on existing understandings of taxonomy, microbial genomes, or other culture-centric paradigms

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Summary

Introduction

The technological leap of DNA sequencing generated a tension between modern metagenomics and historical microbiology. We propose rethinking microbial communities as revealed via DNA sequencing, reimagining what microbial life may be instead of assuming what it is based on existing understandings of taxonomy, microbial genomes, or other culture-centric paradigms. Gaps between metagenomics [4] and historical microbiology illustrate why microbiome scientists should reconsider our core assumptions (Fig. 1A)—though the field

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