Biology subjects

Schwartz, R. S.

Publications and source records attributed to Schwartz, R. S..

3 recordsLinked to original sources

bioRxiv2023

Aging-associated augmentation of gut microbiome virulence capability drives sepsis severity.

Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host, but also reflects longevity-associated changes in the virulence of gut pathobionts. We utilized two complementary models of gut microbiota-induced experimental sepsis to establish the aged gut microbiome as a key pathophysiologic driver of heightened disease severity. Further murine and human investigations into these polymicrobial bacterial communities demonstrated that age was associated with only subtle shifts in ecological composition, but an overabundance of genomic virulence factors that have functional consequence on host immune evasion. One Sentence SummaryThe severity of sepsis in the aged host is in part mediated by longevity-associated increases in gut microbial virulence.

microbiology↗

bioRxiv2021

Interrogating Genomic Data in the Phylogenetic Placement of Treeshrews Reveals Potential Sources of Conflict

The position of some taxa on the Tree of Life remains controversial despite the increase in genomic data used to infer phylogenies. While analyzing large datasets alleviates stochastic errors, it does not prevent systematic errors in inference, caused by both biological (e.g., incomplete lineage sorting, hybridization) and methodological (e.g., incorrect modeling, erroneous orthology assessments) factors. In this study, we systematically investigated factors that could result in these controversies, using the treeshrew (Scandentia, Mammalia) as a study case. Recent studies have narrowed the phylogenetic position of treeshrews to three competing hypotheses: sister to primates and flying lemurs (Primatomorpha), sister to rodents and lagomorphs (Glires), or sister to a clade comprising all of these. We sampled 50 mammal species including three treeshrews, a selection of taxa from the potential sister groups, and outgroups. Using a large diverse set of loci, we assessed support for the alternative phylogenetic position of treeshrews. The results suggest that the data has statistical support for two hypotheses for the placements of treeshrews, sister to Primatomorpha and to Primatomorpha+Glires. While we observe differences in properties of loci of different types (e.g., CDS, intron, etc.) with respect to the strength of the signal, the support for any particular topology is not dependent on the properties of the data. Rather, we show that the method of phylogenetic signal assessment, as well as whether the signal is measured using the full dataset or only loci with the strongest signal, impact the results much more.

evolutionary biology↗

bioRxiv2019

Genome-scale profiling reveals higher proportions of phylogenetic signal in non-coding data

Accurate estimates of species relationships are integral to our understanding of evolution, yet many relationships remain controversial despite whole-genome sequence data. These controversies are due in part to complex patterns of phylogenetic and non-phylogenetic signal coming from regions of the genome experiencing distinct evolutionary forces, which can be difficult to disentangle. Here we profile the amounts and proportions of phylogenetic and non-phylogenetic signal derived from loci spread across mammalian genomes. We identified orthologous sequences from primates, rodents, and pecora, annotated sites as one or more of nine locus types (e.g. coding, intronic, intergenic), and profiled the phylogenetic information contained within locus types across evolutionary timescales associated with each clade. In all cases, non-coding loci provided more overall signal and a higher proportion of phylogenetic signal compared to coding loci. This suggests potential benefits of shifting away from primarily targeting genes or coding regions for phylogenetic studies, particularly in this era of accessible whole genome sequence data. In contrast to long-held assumptions about the phylogenetic utility of more variable genomic regions, most locus types provided relatively consistent phylogenetic information across timescales, although we find evidence that coding and intronic regions may, respectively and to a limited degree, inform disproportionately about older and younger splits. As part of this work we also validate the SISRS pipeline as an annotation-free ortholog discovery pipeline capable of identifying millions of phylogenetically informative sites directly from raw sequencing reads.

bioinformatics↗