Biomedical subjects

Catherine A Lozupone

Publications and source records attributed to Catherine A Lozupone.

4 recordsLinked to original sources

PubMed2026

KG-Microbe: Building modular and scalable knowledge graphs for microbiome and microbial sciences.

BACKGROUND: The integration of many disparate forms of data is essential for understanding the microbial world and its interaction with the environment and human health. Doing so is particularly challenging in the context of microbe-host and microbe-microbe interactions that contribute to health or environmental outcomes. There are thousands of relevant microbial species, and millions of interactions among those microbes and with their environment or host. Integrated information (e.g., about host and microbial physiology, genetics, and metabolism) facilitates deeper understanding of complex mechanisms and helps interpret correlative results. RESULTS: The KG-Microbe construction framework is a novel approach to harmonizing bacterial and archaeal data in the form of a findable, accessible, interoperable, reusable and AI-ready knowledge graph (KG). Starting from a core KG with organismal traits, environments, and growth preferences and the integration of established ontologies, the framework generates a hierarchy of related KGs targeting specific use cases, including the human microbiome in the context of disease, or environmental microbiomes. The framework supports customizable taxa subsets representing communities or clades of interest. Evaluations of the KG-Microbe KGs through a series of competency questions demonstrate the accuracy and effectiveness of the data harmonization, and the utility of the resulting KGs in studies of inflammatory bowel disease and Parkinson's disease. Finally, the predictive and environmental capabilities of the KGs are demonstrated by predicting growth preferences using graph features. CONCLUSIONS: The KG-Microbe framework unifies microbial contexts in a single resource to support integrative analyses across biomedical, host, and environmental domains. KG-Microbe is a flexible, modular enabling technology for humans and machine learning methods to uncover candidate mechanistic explanations of microbial associations.

Microbiota↗

PubMed2007

Quantitative and qualitative beta diversity measures lead to different insights into factors that structure microbial communities.

The assessment of microbial diversity and distribution is a major concern in environmental microbiology. There are two general approaches for measuring community diversity: quantitative measures, which use the abundance of each taxon, and qualitative measures, which use only the presence/absence of data. Quantitative measures are ideally suited to revealing community differences that are due to changes in relative taxon abundance (e.g., when a particular set of taxa flourish because a limiting nutrient source becomes abundant). Qualitative measures are most informative when communities differ primarily by what can live in them (e.g., at high temperatures), in part because abundance information can obscure significant patterns of variation in which taxa are present. We illustrate these principles using two 16S rRNA-based surveys of microbial populations and two phylogenetic measures of community beta diversity: unweighted UniFrac, a qualitative measure, and weighted UniFrac, a new quantitative measure, which we have added to the UniFrac website (http://bmf.colorado.edu/unifrac). These studies considered the relative influences of mineral chemistry, temperature, and geography on microbial community composition in acidic thermal springs in Yellowstone National Park and the influences of obesity and kinship on microbial community composition in the mouse gut. We show that applying qualitative and quantitative measures to the same data set can lead to dramatically different conclusions about the main factors that structure microbial diversity and can provide insight into the nature of community differences. We also demonstrate that both weighted and unweighted UniFrac measurements are robust to the methods used to build the underlying phylogeny.

Animals↗

PubMed2005

Obesity alters gut microbial ecology.

We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals. The sequences reported in this paper have been deposited in the GenBank database [accession nos. DQ 014552--DQ 015671 (mothers) and AY 989911--AY 993908 (offspring)].

Animals↗

PubMed2003

Polymorphism, recombination and alternative unscrambling in the DNA polymerase alpha gene of the ciliate Stylonychia lemnae (Alveolata; class Spirotrichea).

DNA polymerase alpha is the most highly scrambled gene known in stichotrichous ciliates. In its hereditary micronuclear form, it is broken into >40 pieces on two loci at least 3 kb apart. Scrambled genes must be reassembled through developmental DNA rearrangements to yield functioning macronuclear genes, but the mechanism and accuracy of this process are unknown. We describe the first analysis of DNA polymorphism in the macronuclear version of any scrambled gene. Six functional haplotypes obtained from five Eurasian strains of Stylonychia lemnae were highly polymorphic compared to Drosophila genes. Another incompletely unscrambled haplotype was interrupted by frameshift and nonsense mutations but contained more silent mutations than expected by allelic inactivation. In our sample, nucleotide diversity and recombination signals were unexpectedly high within a region encompassing the boundary of the two micronuclear loci. From this and other evidence we infer that both members of a long repeat at the ends of the loci provide alternative substrates for unscrambling in this region. Incongruent genealogies and recombination patterns were also consistent with separation of the two loci by a large genetic distance. Our results suggest that ciliate developmental DNA rearrangements may be more probabilistic and error prone than previously appreciated and constitute a potential source of macronuclear variation. From this perspective we introduce the nonsense-suppression hypothesis for the evolution of ciliate altered genetic codes. We also introduce methods and software to calculate the likelihood of hemizygosity in ciliate haplotype samples and to correct for multiple comparisons in sliding-window analyses of Tajima's D.

Animals↗