1. Genetics and Genomics
  2. Microbiology and Infectious Disease
Download icon

A phylogenetic transform enhances analysis of compositional microbiota data

  1. Justin D Silverman
  2. Alex D Washburne
  3. Sayan Mukherjee
  4. Lawrence A David  Is a corresponding author
  1. Duke University, United States
Tools and Resources
  • Cited 101
  • Views 9,429
  • Annotations
Cite this article as: eLife 2017;6:e21887 doi: 10.7554/eLife.21887

Abstract

Surveys of microbial communities (microbiota), typically measured as relative abundance of species, have illustrated the importance of these communities in human health and disease. Yet, statistical artifacts commonly plague the analysis of relative abundance data. Here, we introduce the PhILR transform, which incorporates microbial evolutionary models with the isometric log-ratio transform to allow off-the-shelf statistical tools to be safely applied to microbiota surveys. We demonstrate that analyses of community-level structure can be applied to PhILR transformed data with performance on benchmarks rivaling or surpassing standard tools. Additionally, By decomposing distance in the PhILR transformed space, we identified neighboring clades that may have adapted to distinct human body sites. Decomposing variance revealed that covariation of bacterial clades within human body sites increases with phylogenetic relatedness. Together, these findings illustrate how the PhILR transform combines statistical and phylogenetic models to overcome compositional data challenges and enable evolutionary insights relevant to microbial communities.

Data availability

The following previously published data sets were used
    1. Human Microbiome Project Consortium
    (2010) Human Microbiome Project
    Publicly available at HMPDACC (v35 download of files 6, 9, and 10).
    1. Costello EK
    2. Lauber CL
    3. Hamady M
    4. Fierer N
    5. Gordon JI
    6. Knight R
    (2009) Costello Skin Sites
    Publicly available as part of the FEMS Benchmark dataset (2011) provided Dan Knights.

Article and author information

Author details

  1. Justin D Silverman

    Program in Computational Biology and Bioinformatics, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3063-2098
  2. Alex D Washburne

    Nicholas School of the Environment, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sayan Mukherjee

    Program in Computational Biology and Bioinformatics, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Lawrence A David

    Program in Computational Biology and Bioinformatics, Duke University, Durham, United States
    For correspondence
    lawrence.david@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3570-4767

Funding

Global Probiotics Council (Young Investigator Grant for Probiotics Research)

  • Lawrence A David

Searle Scholars Program (15-SSP-184 Research Agreement)

  • Lawrence A David

Alfred P. Sloan Foundation (BR2014-003)

  • Lawrence A David

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Anthony Fodor, University of North Carolina at Charlotte

Publication history

  1. Received: September 27, 2016
  2. Accepted: February 13, 2017
  3. Accepted Manuscript published: February 15, 2017 (version 1)
  4. Version of Record published: February 27, 2017 (version 2)

Copyright

© 2017, Silverman et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 9,429
    Page views
  • 1,522
    Downloads
  • 101
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Developmental Biology
    2. Genetics and Genomics
    Juliet R Girard et al.
    Research Article Updated

    Mechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type-specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single-cell RNA-Seq, and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, and inhibits canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis.

    1. Cancer Biology
    2. Genetics and Genomics
    Andrew S McNeal et al.
    Research Article

    Benign melanocytic nevi frequently emerge when an acquired BRAFV600E mutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence in melanocytic nevus formation, necessitating investigations into alternative mechanisms for the establishment and maintenance of proliferation arrest in nevi. We compared the transcriptomes of melanocytes from healthy human skin, nevi, and melanomas arising from nevi and identified a set of microRNAs as highly expressed nevus-enriched transcripts. Two of these microRNAs—MIR211-5p and MIR328-3p—induced mitotic failure, genome duplication, and proliferation arrest in human melanocytes through convergent targeting of AURKB. We demonstrate that BRAFV600E induces a similar proliferation arrest in primary human melanocytes that is both reversible and conditional. Specifically, BRAFV600E expression stimulates either arrest or proliferation depending on the differentiation state of the melanocyte. We report genome duplication in human melanocytic nevi, reciprocal expression of AURKB and microRNAs in nevi and melanomas, and rescue of arrested human nevus cells with AURKB expression. Taken together, our data describe an alternative molecular mechanism for melanocytic nevus formation that is congruent with both experimental and clinical observations.