Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


  • NSF Public Access
  • Search Results
  • MetaPop: a pipeline for macro- and microdiversity analyses and visualization of microbial and viral metagenome-derived populations
Title: MetaPop: a pipeline for macro- and microdiversity analyses and visualization of microbial and viral metagenome-derived populations
Abstract Background Microbes and their viruses are hidden engines driving Earth’s ecosystems from the oceans and soils to humans and bioreactors. Though gene marker approaches can now be complemented by genome-resolved studies of inter-(macrodiversity) and intra-(microdiversity) population variation, analytical tools to do so remain scattered or under-developed. Results Here, we introduce MetaPop, an open-source bioinformatic pipeline that provides a single interface to analyze and visualize microbial and viral community metagenomes at both the macro - and microdiversity levels. Macrodiversity estimates include population abundances and α- and β-diversity. Microdiversity calculations include identification of single nucleotide polymorphisms, novel codon-constrained linkage of SNPs, nucleotide diversity ( π and θ ), and selective pressures (pN/pS and Tajima’s D ) within and fixation indices ( F ST ) between populations. MetaPop will also identify genes with distinct codon usage. Following rigorous validation, we applied MetaPop to the gut viromes of autistic children that underwent fecal microbiota transfers and their neurotypical peers. The macrodiversity results confirmed our prior findings for viral populations (microbial shotgun metagenomes were not available) that diversity did not significantly differ between autistic and neurotypical children. However, by also quantifying microdiversity, MetaPop revealed lower average viral nucleotide diversity ( π ) in autistic children. Analysis of the percentage of genomes detected under positive selection was also lower among autistic children, suggesting that higher viral π in neurotypical children may be beneficial because it allows populations to better “bet hedge” in changing environments. Further, comparisons of microdiversity pre- and post-FMT in autistic children revealed that the delivery FMT method (oral versus rectal) may influence viral activity and engraftment of microdiverse viral populations, with children who received their FMT rectally having higher microdiversity post-FMT. Overall, these results show that analyses at the macro level alone can miss important biological differences. Conclusions These findings suggest that standardized population and genetic variation analyses will be invaluable for maximizing biological inference, and MetaPop provides a convenient tool package to explore the dual impact of macro - and microdiversity across microbial communities.  more » « less
Award ID(s):
1759831 1759874
PAR ID:
10354254
Author(s) / Creator(s):
; ; ; ; ; ;
Date Published:
Journal Name:
Microbiome
Volume:
10
Issue:
1
ISSN:
2049-2618
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; (, Nature Biotechnology)
    null (Ed.)
    Coexisting microbial cells of the same species often exhibit genetic variation that can affect phenotypes ranging from nutrient preference to pathogenicity. Here we present inStrain, a program that uses metagenomic paired reads to profile intra-population genetic diversity (microdiversity) across whole genomes and compares microbial populations in a microdiversity-aware man- ner, greatly increasing the accuracy of genomic comparisons when benchmarked against existing methods. We use inStrain to profile >1,000 fecal metagenomes from newborn premature infants and find that siblings share significantly more strains than unrelated infants, although identical twins share no more strains than fraternal siblings. Infants born by cesarean section har- bor Klebsiella with significantly higher nucleotide diversity than infants delivered vaginally, potentially reflecting acquisition from hospital rather than maternal microbiomes. Genomic loci that show diversity in individual infants include variants found between other infants, possibly reflecting inoculation from diverse hospital-associated sources. inStrain can be applied to any metagenomic dataset for microdiversity analysis and rigorous strain comparison. 
    more » « less
  2. ; ; ; ; ; ; ; ; ; ; et al (, bioRxiv)
    null (Ed.)
    The extent and ecological significance of intraspecific diversity within marine microbial populations is still poorly understood, and it remains unclear if such strain-level microdiversity will affect fitness and persistence in a rapidly changing ocean environment. In this study, we cultured 11 sympatric strains of the ubiquitous marine picocyanobacterium Synechococcus isolated from a Narragansett Bay (Rhode Island, USA) phytoplankton community thermal selection experiment. Despite all 11 isolates being highly similar (with average nucleotide identities of >99.9%, with 98.6-100% of the genome aligning), thermal performance curves revealed selection at warm and cool temperatures had subdivided the initial population into thermotypes with pronounced differences in maximum growth temperatures. Within the fine-scale genetic diversity that did exist within this population, the two divergent thermal ecotypes differed at a locus containing genes for the phycobilisome antenna complex. Our study demonstrates that present-day marine microbial populations can contain microdiversity in the form of cryptic but environmentally-relevant thermotypes that may increase their resilience to future rising temperatures. 
    more » « less
  3. ; ; ; ; ; ; ; ; ; ; et al (, Proceedings of the National Academy of Sciences)
    The extent and ecological significance of intraspecific functional diversity within marine microbial populations is still poorly understood, and it remains unclear if such strain-level microdiversity will affect fitness and persistence in a rapidly changing ocean environment. In this study, we cultured 11 sympatric strains of the ubiquitous marine picocyanobacteriumSynechococcusisolated from a Narragansett Bay (RI) phytoplankton community thermal selection experiment. Thermal performance curves revealed selection at cool and warm temperatures had subdivided the initial population into thermotypes with pronounced differences in maximum growth temperatures. Curiously, the genomes of all 11 isolates were almost identical (average nucleotide identities of >99.99%, with >99% of the genome aligning) and no differences in gene content or single nucleotide variants were associated with either cool or warm temperature phenotypes. Despite a very high level of genomic similarity, sequenced epigenomes for two strains showed differences in methylation on genes associated with photosynthesis. These corresponded to measured differences in photophysiology, suggesting a potential pathway for future mechanistic research into thermal microdiversity. Our study demonstrates that present-day marine microbial populations can harbor cryptic but environmentally relevant thermotypes which may increase their resilience to future rising temperatures. 
    more » « less
  4. ; ; ; (, Molecular Biology and Evolution)
    Harris, Kelley (Ed.)
    Abstract Many commonly studied species now have more than one chromosome-scale genome assembly, revealing a large amount of genetic diversity previously missed by approaches that map short reads to a single reference. However, many species still lack multiple reference genomes and correctly aligning references to build pangenomes can be challenging for many species, limiting our ability to study this missing genomic variation in population genetics. Here, we argue that k-mers are a very useful but underutilized tool for bridging the reference-focused paradigms of population genetics with the reference-free paradigms of pangenomics. We review current literature on the uses of k-mers for performing three core components of most population genetics analyses: identifying, measuring, and explaining patterns of genetic variation. We also demonstrate how different k-mer-based measures of genetic variation behave in population genetic simulations according to the choice of k, depth of sequencing coverage, and degree of data compression. Overall, we find that k-mer-based measures of genetic diversity scale consistently with pairwise nucleotide diversity (π) up to values of about π=0.025 (R2=0.97) for neutrally evolving populations. For populations with even more variation, using shorter k-mers will maintain the scalability up to at least π=0.1. Furthermore, in our simulated populations, k-mer dissimilarity values can be reliably approximated from counting bloom filters, highlighting a potential avenue to decreasing the memory burden of k-mer-based genomic dissimilarity analyses. For future studies, there is a great opportunity to further develop methods to identifying selected loci using k-mers. 
    more » « less
  5. ; (, Proceedings of the Annual Conference of the Cognitive Science Society)
    Autistic and neurotypical children do not handle audiovisual speech in the same manner. Current evidence suggests that this difference occurs at the level of cue combination. Here, we test whether differences in autistic and neurotypical audiovisual speech perception can be explained by a neural theory of sensory perception in autism, which proposes that heightened levels of neural excitation can account for sensory differences in autism. Through a linking hypothesis that integrates a standard probabilistic cognitive model of cue integration with representations of neural activity, we derive a model that can simulate audio-visual speech perception at a neural population level. Simulations of an audiovisual lexical identification task demonstrate that heightened levels of neural excitation at the level of cue combination cannot account for the observed differences in autistic and neurotypical children's audiovisual speech perception. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Text Encoded Conversion
  • XML
  • Save / Share this Record
  • Send to Email