Biology subjects

Odom, A. R.

Publications and source records attributed to Odom, A. R..

3 recordsLinked to original sources

bioRxiv2025

Defining the Mycobacterium tuberculosis Pangenome and Suggestions for a New Composite Reference Sequence

Mycobacterium tuberculosis (Mtb) causes tuberculosis (TB), a global disease with diverse clinical and microbiological manifestations. Studies into the biological causes of this phenotypic diversity have been largely limited to a few reference strains. A pangenome approach is likely to provide new insights. Pangenomic tuberculosis studies have been limited the availability of only fragmented genome sequences and error-prone reference genomes. We used a de novo assembly pipeline that generates extremely complete and accurate whole genome sequences to generate 50 closed Mtb genomes across all seven major lineages. We identified 3,377 core gene clusters and 379 accessory clusters. Analysis showed multi-copy core clusters were largely due to gene fragmentation (76%), paralogs (12%), nearly identical gene duplications (4%), or combinations (8%). Sixteen hypervariable regions (HVRs) were identified, including novel paralogs and variable PE/PPE genes. We consolidated these findings into a Pangenome Gene Reference Resource (PGRR) for precision alignment. Our study demonstrates the closed nature of the Mtb pangenome, with most variation in accessory genes and HVRs. The PGRR provides a foundation for improved drug/vaccine target discovery and highlights the need to move beyond the commonly used H37Rv strain to study Mtb genetic and phenotypic diversity. IMPORTANCETuberculosis (TB), caused by Mycobacterium tuberculosis, affects millions globally. Genetic differences among Mtb strains have been difficult to resolve due to incomplete genome references. We sequenced and analyzed complete genomes of 50 Mtb strains from all lineages, identifying 16 hypervariable regions and 3,498 core gene clusters whose diversity mostly stemmed from gene fragmentation, paralog duplication and deletion events and differences in the PE/PPE gene family representation. These differences may explain many of the varied clinical manifestations of TB. We created Pangenome Gene Reference Resource to unify genetic data for precise comparison studies to aid in developing new drugs vaccines and other interventions against this disease.

microbiology↗

bioRxiv2025

MetaScope: A High-Resolution Framework for Species-Level 16S Metataxonomic Classification

Accurate species-level classification of microbial communities remains a major challenge in microbiome analysis, particularly when using traditional 16S rRNA amplicon sequencing pipelines such as QIIME2 and DADA2. These methods often fail to resolve taxonomy beyond the genus level due to limitations in clustering algorithms and ambiguous marker genes. To address this, we present MetaScope, a modular, R-based software package that reimplements and extends the PathoScope 2.0 framework for high-resolution microbial classification. MetaScope introduces two key innovations: (1) the integration of user-defined or empirical prior weights into the Bayesian read reassignment algorithm to improve abundance estimation, and (2) MetaBlast, a secondary BLAST-based validation module for refining species-level assignments. Benchmarking against mock and clinical datasets demonstrates that MetaScope significantly outperforms QIIME2 and DADA2, achieving up to 93.6% species-level classification accuracy. This translates to offering enhanced resolution for downstream analyses such as ecological diversity metrics. These results highlight MetaScope as a powerful tool for advancing microbial community profiling in both research and clinical settings.

bioinformatics↗

bioRxiv2023

Analysis of nasopharyngeal microbiome patterns in Zambian infants with fatal acute febrile illness

IntroductionAssociative connections have previously been identified between nasopharyngeal infections and infant mortality. The nasopharyngeal microbiome may potentially influence the severity of these infections. MethodsWe conducted an analysis of a longitudinal prospective cohort study of 1,981 infants who underwent nasopharyngeal sampling from 1 week through 14 weeks of age at 2-3-week intervals. In all, 27 microbiome samples from 9 of the infants in the cohort who developed fatal acute febrile illness (fAFI) were analyzed in pooled comparisons with 69 samples from 10 healthy comparator infants. We completed 16S rRNA amplicon gene sequencing all infant NP samples and characterized the maturation of the infant NP microbiome among the fAFI(+) and fAFI(-) infant cohorts. ResultsBeta diversity measures of fAFI(-) infants were markedly higher than those of fAFI(+) infants. The fAFI(+) infant NP microbiome was marked by higher abundances of Escherichia, Pseudomonas, Leuconostoc, and Weissella, with low relative presence of Alkalibacterium, Dolosigranulum, Moraxella, and Streptococcus. ConclusionsOur results suggest that nasopharyngeal microbiome dysbiosis precedes fAFI in young infants. Early dysbiosis, involving microbes such as Escherichia, may play a role in the causal pathway leading to fAFI or could be a marker of other pathogenic forces that directly lead to fAFI.

microbiology↗