MSPminer: abundance-based reconstitution of microbial pan-genomes from shotgun metagenomic data

Abstract

Motivation Analysis toolkits for shotgun metagenomic data achieve strain-level characterization of complex microbial communities by capturing intra-species gene content variation. Yet, these tools are hampered by the extent of reference genomes that are far from covering all microbial variability, as many species are still not sequenced or have only few strains available. Binning co-abundant genes obtained from de novo assembly is a powerful reference-free technique to discover and reconstitute gene repertoire of microbial species. While current methods accurately identify species core parts, they miss many accessory genes or split them into small gene groups that remain unassociated to core clusters. Results We introduce MSPminer, a computationally efficient software tool that reconstitutes Metagenomic Species Pan-genomes (MSPs) by binning co-abundant genes across metagenomic samples. MSPminer relies on a new robust measure of proportionality coupled with an empirical classifier to group and distinguish not only species core genes but accessory genes also. Applied to a large scale metagenomic dataset, MSPminer successfully delineates in a few hours the gene repertoires of 1661 microbial species with similar specificity and higher sensitivity than existing tools. The taxonomic annotation of MSPs reveals microorganisms hitherto unknown and brings coherence in the nomenclature of the species of the human gut microbiota. The provided MSPs can be readily used for taxonomic profiling and biomarkers discovery in human gut metagenomic samples. In addition, MSPminer can be applied on gene count tables from other ecosystems to perform similar analyses. Availability and implementation The binary is freely available for non-commercial users at www.enterome.com/downloads . Supplementary information Supplementary data are available at Bioinformatics online.

Incorporating Phylogenetic Information in Microbiome Differential Abundance Studies Has No Effect on Detection Power and FDR Control

“…Divisive and threshold-free agglomerative approaches achieve finer taxonomic resolutions than the threshold-based similarity approach. Using WGS in the ecosystems where a bacterial gene catalog is available, such as the human gut or the pig gut (Xiao et al, 2016), the standard approach consists in mapping the reads against the catalog and then clustering the bacterial genes based on their abundance profiles to produce metagenomic species (MGS) (Nielsen et al, 2014) or clusters of coabundant genes to reconstruct microbial pan-genomes (MSP) (Plaza Oñate et al, 2018). We will refer to taxa, noting that the term can designate OTUs, ASVs, oligotypes, MGSs, MSPs and generally any feature found in abundance tables (obtained by counting the number of copies of each feature in each sample).…”

Gut microbiome, diet and symptom interactions in irritable bowel syndrome

“…Next, whole-metagenomic sequencing was performed on 138 individuals (102 IBS patients and 36 healthy subjects) (Table 1). Metagenomic reads (with an average of 14 million reads per sample) were mapped onto a catalog of Metagenomic Species Pangenomes (MSPs) 27 , yielding a total of 1,661 MSPs. On the basis of per-individual genetic content, 166 of them were further divided into 523 subspecies, corresponding to a mean of 75.3% of the metagenome read mass.…”

“…Metagenomics species pangenomes (MSPs) are co-abundant gene groups that can be considered part of complete microbial species pangenomes. MSP gene content was extracted from a previous publication by Plaza-Onate et al 27 . MSP gene content was subdivided into core and accessory genes.…”

Incorporating phylogenetic information in microbiome abundance studies has no effect on detection power and FDR control

“…Finally, the Zeller MSP data originates from the same study as the Zeller data (Zeller et al, 2014). It was created from the shotgun data by reconstructing Metagenomics Species Pan-genomes (MSPs) abundance count table, as reported in Plaza Oñate et al (2018). Briefly, reads were quality-filtered and unique reads were mapped against the 9.9 million Integrated Gene Catalog (Li et al, 2014) using BBmap (Bushnell, 2014).…”

“…Divisive and threshold-free agglomerative approaches achieve finer taxonomic resolutions than the threshold-based similarity approach. Using WGS in the ecosystems where a bacterial gene catalog is available, such as the human gut (Li et al, 2014) or the pig gut (Xiao et al, 2016), the standard approach consists in mapping the reads against the catalog and then clustering the bacterial genes based on their abundance profiles to produce metagenomic species (MGS) (Nielsen et al, 2014) or clusters of co-abundant genes to reconstruct microbial pan-genomes (MSP) (Plaza Oñate et al, 2018). We will refer to taxa, noting that the term can designate OTUs, ASVs, oligotypes, MGSs, MSPs and generally any feature found in abundance tables.…”