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Sullivan, Matthew B. (ORCID:0000000183988234)

Publications and source records attributed to Sullivan, Matthew B. (ORCID:0000000183988234).

10 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

STREAMS guidelines: standards for technical reporting in environmental and host-associated microbiome studies

The interdisciplinary nature of microbiome research, coupled with the generation of complex multi-omics data, makes knowledge sharing challenging. The Strengthening the Organization and Reporting of Microbiome Studies (STORMS) guidelines provide a checklist for the reporting of study information, experimental design and analytical methods within a scientific manuscript on human microbiome research. Here, in this Consensus Statement, we present the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines. The guidelines expand on STORMS and include 67 items to support the reporting and review of environmental (for example, terrestrial, aquatic, atmospheric and engineered), synthetic and non-human host-associated microbiome studies in a standardized and machine-actionable manner. Based on input from 248 researchers spanning 28 countries, we provide detailed guidance, including comparisons with STORMS, and case studies that demonstrate the usage of the STREAMS guidelines. In conclusion, STREAMS, like STORMS, will be a living community resource updated by the Consortium with consensus-building input of the broader community.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Infection and Genomic Properties of Single- and Double-Stranded DNA Cellulophaga Phages

Bacterial viruses (phages) are abundant and ecologically impactful, but laboratory-based experimental model systems vastly under-represent known phage diversity, particularly for ssDNA phages. Here, we characterize the genomes and infection properties of two unrelated marine flavophages—ssDNA generalist phage phi18:4 (6.5 Kbp) and dsDNA specialist phage phi18:1 (39.2 Kbp)—when infecting the same Cellulophaga baltica strain #18 (Cba18), of the class Flavobacteriia. Phage phi18:4 belongs to a new family of ssDNA phages, has an internal lipid membrane, and its genome encodes primarily structural proteins, as well as a DNA replication protein common to ssDNA phages and a unique lysis protein. Phage phi18:1 is a siphovirus that encodes several virulence genes, despite not having a known temperate lifestyle, a CAZy enzyme likely for regulatory purposes, and four DNA methyltransferases dispersed throughout the genome that suggest both host modulation and phage DNA protection against host restriction. Physiologically, ssDNA phage phi18:4 has a shorter latent period and smaller burst size than dsDNA phage phi18:1, and both phages efficiently infect this host. These results help augment the diversity of characterized environmental phage–host model systems by studying infections of genomically diverse phages (ssDNA vs. dsDNA) on the same host.

Howard-Varona, Cristina (ORCID:0000000241495818)↗
DOE OSTI2024

Microbial polyphenol metabolism is part of the thawing permafrost carbon cycle

Abstract With rising global temperatures, permafrost carbon stores are vulnerable to microbial degradation. The enzyme latch theory states that polyphenols should accumulate in saturated peatlands due to diminished phenol oxidase activity, inhibiting resident microbes and promoting carbon stabilization. Pairing microbiome and geochemical measurements along a permafrost thaw-induced saturation gradient in Stordalen Mire, a model Arctic peatland, we confirmed a negative relationship between phenol oxidase expression and saturation but failed to support other trends predicted by the enzyme latch. To inventory alternative polyphenol removal strategies, we built CAMPER, a gene annotation tool leveraging polyphenol enzyme knowledge gleaned across microbial ecosystems. Applying CAMPER to genome-resolved metatranscriptomes, we identified genes for diverse polyphenol-active enzymes expressed by various microbial lineages under a range of redox conditions. This shifts the paradigm that polyphenols stabilize carbon in saturated soils and highlights the need to consider both oxic and anoxic polyphenol metabolisms to understand carbon cycling in changing ecosystems.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Single-molecule epitranscriptomic analysis of full-length HIV-1 RNAs reveals functional roles of site-specific m6As

Abstract Although the significance of chemical modifications on RNA is acknowledged, the evolutionary benefits and specific roles in human immunodeficiency virus (HIV-1) replication remain elusive. Most studies have provided only population-averaged values of modifications for fragmented RNAs at low resolution and have relied on indirect analyses of phenotypic effects by perturbing host effectors. Here we analysed chemical modifications on HIV-1 RNAs at the full-length, single RNA level and nucleotide resolution using direct RNA sequencing methods. Our data reveal an unexpectedly simple HIV-1 modification landscape, highlighting three predominant N 6 -methyladenosine (m 6 A) modifications near the 3′ end. More densely installed in spliced viral messenger RNAs than in genomic RNAs, these m 6 As play a crucial role in maintaining normal levels of HIV-1 RNA splicing and translation. HIV-1 generates diverse RNA subspecies with distinct m 6 A ensembles, and maintaining multiple of these m 6 As on its RNAs provides additional stability and resilience to HIV-1 replication, suggesting an unexplored viral RNA-level evolutionary strategy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

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.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

iVirus 2.0: Cyberinfrastructure-supported tools and data to power DNA virus ecology

Microbes drive myriad ecosystem processes, but under strong influence from viruses. Because studying viruses in complex systems requires different tools than those for microbes, they remain underexplored. To combat this, we previously aggregated double-stranded DNA (dsDNA) virus analysis capabilities and resources into ‘iVirus’ on the CyVerse collaborative cyberinfrastructure. Here we substantially expand iVirus’s functionality and accessibility, to iVirus 2.0, as follows. First, core iVirus apps were integrated into the Department of Energy’s Systems Biology KnowledgeBase (KBase) to provide an additional analytical platform. Second, at CyVerse, 20 software tools (apps) were upgraded or added as new tools and capabilities. Third, nearly 20-fold more sequence reads were aggregated to capture new data and environments. Finally, documentation, as “live” protocols, was updated to maximize user interaction with and contribution to infrastructure development. Together, iVirus 2.0 serves as a uniquely central and accessible analytical platform for studying how viruses, particularly dsDNA viruses, impact diverse microbial ecosystems.

Bolduc, Benjamin (ORCID:0000000324200755)↗
DOE OSTI2021

VirSorter2: a multi-classifier, expert-guided approach to detect diverse DNA and RNA viruses

Abstract Background Viruses are a significant player in many biosphere and human ecosystems, but most signals remain “hidden” in metagenomic/metatranscriptomic sequence datasets due to the lack of universal gene markers, database representatives, and insufficiently advanced identification tools. Results Here, we introduce VirSorter2, a DNA and RNA virus identification tool that leverages genome-informed database advances across a collection of customized automatic classifiers to improve the accuracy and range of virus sequence detection. When benchmarked against genomes from both isolated and uncultivated viruses, VirSorter2 uniquely performed consistently with high accuracy (F1-score > 0.8) across viral diversity, while all other tools under-detected viruses outside of the group most represented in reference databases (i.e., those in the order Caudovirales ). Among the tools evaluated, VirSorter2 was also uniquely able to minimize errors associated with atypical cellular sequences including eukaryotic genomes and plasmids. Finally, as the virosphere exploration unravels novel viral sequences, VirSorter2’s modular design makes it inherently able to expand to new types of viruses via the design of new classifiers to maintain maximal sensitivity and specificity. Conclusion With multi-classifier and modular design, VirSorter2 demonstrates higher overall accuracy across major viral groups and will advance our knowledge of virus evolution, diversity, and virus-microbe interaction in various ecosystems. Source code of VirSorter2 is freely available ( https://bitbucket.org/MAVERICLab/virsorter2 ), and VirSorter2 is also available both on bioconda and as an iVirus app on CyVerse ( https://de.cyverse.org/de ).

59 BASIC BIOLOGICAL SCIENCES↗