Biology subjects

Alisoltani, A.

Publications and source records attributed to Alisoltani, A..

6 recordsLinked to original sources

bioRxiv2026

Taxonomic Resolution of 16S rRNA, FastANI, Mash, and FastAAI across 30,495 Prokaryotic Type-Strain Genomes

Prokaryotic taxonomy now relies on both marker-gene and genome-wide sequence comparisons, but these methods differ in taxonomic range, scalability, and sensitivity to genome quality. Here, we benchmarked four commonly used approaches, including 16S rRNA identity, FastANI, Mash distance, and FastAAI/Jaccard similarity across a dataset of 30,495 prokaryotic type-strain genomes. Type-strain genomes provide nomenclatural anchors for validly named species, making them a useful framework for evaluating how sequence-based methods correspond to current taxonomic assignments. We evaluated method behavior across taxonomic ranks from species to domain and separated initial method failures from threshold-based failures. When clean full-length 16S rRNA sequences were available, same-species comparisons passed the empirical threshold in >97% of cases. However, a usable full-length 16S rRNA sequence was unavailable for 4,551 of the 16,402 same-species comparisons (28%), limiting marker-gene-based analysis. In addition, 16S rRNA identity ranges overlapped across higher taxonomic ranks, limiting the use of universal rank-specific cutoffs. FastANI provided strong species-level resolution, with same-species comparisons passing the empirical threshold in approximately 88% of cases but was less informative at deeper ranks. Mash enabled rapid genome-scale screening, although its distance values require careful interpretation beyond close relatives. FastAAI provided a genome-wide amino-acid signal, with approximately 92% of same-species comparisons passing the empirical threshold and was especially useful for comparisons beyond the species boundary. Overall, no single method performed optimally across all taxonomic levels. These results support a rank-aware benchmarking framework in which 16S rRNA, FastANI, Mash, and FastAAI are interpreted as complementary tools, with attention to genome quality, missing data, and method-specific failure modes.

genomics↗

bioRxiv2023

Pan-genome study underling the extent of genomic variation of invasive Streptococcus pneumoniae in Malawi

AbstractStreptococcus pneumoniae is a common cause of acute bacterial infections in Malawi. Understanding the molecular mechanisms underlying its invasive behavior is crucial for designing new therapeutic strategies. We conducted a pan-genome analysis to identify potential virulence genes in S. pneumoniae by comparing the gene pool of isolates from carriers nasopharyngeal secretions to isolates from the blood and cerebrospinal fluid of patients. Our analysis involved 1,477 pneumococcal isolates from Malawi, comprising 825 samples from carriers (nasopharyngeal swab) and 652 from patients (368 from blood and 284 from cerebrospinal fluid). We identified 56 serotypes in the cohort. While most serotypes exhibited a similar prevalence in both carriage and disease groups, serotypes 1 and 5, the most abundant serotypes in the entire cohort, were significantly more commonly detected in specimens from patients compared to the carriage group. This difference is presumably due to their shorter nasopharyngeal colonization period. Furthermore, these serotypes displayed genetic distinctiveness from other serotypes. A magnificent genetic difference was observed in the absence of genes from the RD8a genomic island in serotypes 1 and 5 compared to significantly prevalent serotypes in the nasopharynx. RD8a genes play pivotal roles in binding to epithelial cells and performing aerobic respiration to synthesize ATP through oxidative phosphorylation. The absence of RD8a from serotypes 1 and 5 may be associated with a shorter duration in the nasopharynx, theoretically due to a reduced capacity to bind to epithelial cells and access free oxygen molecules required for aerobic respiration (essential to maintain the carriage state). Serotypes 1 and 5, significantly harbor operons that encode phosphoenolpyruvate phosphotransferase systems, which might relate to transporting carbohydrates, relying on phosphoenolpyruvate as the energy source instead of ATP. In conclusion, serotypes 1 and 5 as the most prevalent invasive pneumococcal strains in Malawi, displayed considerable genetic divergence from other strains, which may offer insights into their invasiveness and potential avenues for further research. Author summaryDespite introducing the pneumococcal conjugate vaccine in 2011, Streptococcus pneumoniae remains a major cause of bacterial infection in Malawi. Whilst some pneumococcal strains harmlessly colonize the nasopharynx, others find their way into normally sterile sites, such as lungs, blood, and nervous system, resulting in serious illness. Our study identified specific pneumococcal serotypes as the most invasive in Malawi, characterized by a short colonization period and significant genetic distinctiveness from other strains. This genetic divergence notably included the absence of several genes associated with aerobic respiration and the presence of genes facilitating ATP-independent carbohydrate transport. The presence or absence of these genes may underlie their heightened invasiveness and shorter colonization period. This hypothesis positions these genes as potential candidates for future therapeutic research. We propose that the specific gene gain and/or loss in invasive versus other serotypes may be linked to the development of invasive pneumococcal diseases. Impact StatementOur research applied pan-genomics principles to comprehensively assess diversity within the pneumococcus genome, with the primary objective of identifying pneumococcal virulence genes for advancing vaccine design and drug development. Within this study, we identified Serotypes 1 and 5 as the predominant and highly invasive pneumococcal strains in Malawi, characterized by a short nasopharyngeal colonization period, suggesting their potential for rapid infection of sterile sites within the human body such as blood and the central nervous system. These serotypes exhibited significant genetic divergence from other serotypes in Malawi, notably lacking key genes within the RD8a operon while harboring transporters functioning independently of ATP. Its important to note that these findings are based on computational analysis, and further validation through laboratory experiments is essential to confirm their biological significance and potential clinical applications. The implications of our research offer potential avenues for more effective pneumococcal disease prevention and treatment, not only in Malawi but also in regions facing similar challenges.

microbiology↗

bioRxiv2021

Increased frequency of recurrent in-frame deletions in new expanding lineages of SARS CoV-2 reflects immune selective pressure

Most of the attention in the surveillance of evolution of SARS-CoV-2 has been centered on single nucleotide substitutions in the spike glycoprotein. We show that in-frame deletions (IFDs) also play a significant role in the evolution of viral genome. The percentage of genomes and lineages with IFDs is growing rapidly and they co-occur independently in multiple lineages, including emerging variants of concerns. IFDs distribution is correlated with spike mutations associated with immune escape and concentrated in proteins involved in interactions with the host immune system. Structural analysis suggests that IFDs remodel viral proteins surfaces at common epitopes and interaction interfaces, affecting the virus interactions with the immune system. We hypothesize that the increased frequency of IFDs is an adaptive response to elevated global population immunity. SummaryMonitoring of SARS-CoV-2 genome evolution uncovers increased frequency and non-random distribution of in-frame deletions in recently emerged lineages.

evolutionary biology↗

bioRxiv2020

The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins

Fast evolution of the SARS-CoV-2 virus provides us with unique information about the patterns of genetic changes in a single pathogen in the timescale of months. This data is used extensively to track the phylodynamic of the pandemics spread and its split into distinct clades. Here we show that the patterns of SARS-CoV-2 virus mutations along its genome are closely correlated with the structural features of the coded proteins. We show that the foldability of proteins 3D structures and conservation of their functions are the universal factors driving evolutionary selection in protein-coding genes. Insights from the analysis of mutation distribution in the context of the SARS-CoV-2 proteins structures and functions have practical implications including evaluating potential antigen epitopes or selection of primers for PCR-based COVID-19 tests.

evolutionary biology↗

bioRxiv2020

Microbial function and genital inflammation in young South African women at high risk of HIV infection

BackgroundFemale genital tract (FGT) inflammation is an important risk factor for HIV acquisition. The FGT microbiome is closely associated with inflammatory profile, however, the relative importance of microbial activities has not been established. Since proteins are key elements representing actual microbial functions, this study utilized metaproteomics to evaluate the relationship between FGT microbial function and inflammation in 113 young and adolescent South African women at high risk of HIV infection. Women were grouped as having low, medium or high FGT inflammation by K-means clustering according to pro-inflammatory cytokine concentrations. ResultsA total of 3,186 microbial and human proteins were identified in lateral vaginal wall swabs using liquid chromatography-tandem mass spectrometry, while 94 microbial taxa were included in the taxonomic analysis. Both metaproteomics and 16S rRNA gene sequencing analyses showed increased non-optimal bacteria and decreased lactobacilli in women with FGT inflammatory profiles. However, differences in the predicted relative abundance of most bacteria were observed between 16S rRNA gene sequencing and metaproteomics analyses. Bacterial protein functional annotations (gene ontology) predicted inflammatory cytokine profiles more accurately than bacterial relative abundance determined by 16S rRNA gene sequence analysis, as well as functional predictions based on 16S rRNA gene sequence data (p<0.0001). The majority of microbial biological processes were underrepresented in women with high inflammation compared to those with low inflammation, including a Lactobacillus-associated signature of reduced cell wall organization and peptidoglycan biosynthesis. This signature remained associated with high FGT inflammation in a subset of 74 women nine weeks later, was upheld after adjusting for Lactobacillus relative abundance, and was associated with in vitro inflammatory cytokine responses to Lactobacillus isolates from the same women. Reduced cell wall organization and peptidoglycan biosynthesis were also associated with high FGT inflammation in an independent sample of ten women. ConclusionsBoth the presence of specific microbial taxa in the FGT and their properties and activities are critical determinants of FGT inflammation. Our findings support those of previous studies suggesting that peptidoglycan is directly immunosuppressive, and identify a possible avenue for biotherapeutic development to reduce inflammation in the FGT. To facilitate further investigations of microbial activities, we have developed the FGT-METAP application that is available at (http://immunodb.org/FGTMetap/).

microbiology↗

bioRxiv2020

Large scale analysis of smoking-induced changes in the tumor immune microenvironment

Tobacco smoke is a known carcinogen, mostly due to its genotoxicity, but its effects on the host immune system are also playing an important role. Here, we leveraged recent results on the immune landscape of cancer based on The Cancer Genomic Atlas (TCGA) data analysis and compared the proportions of major classes of tumor-infiltrating immune cells (TIICs) between smokers and never smokers in ten TCGA cancer types. We show that statistically significant changes can be identified in all ten cancers, with increased plasma cell populations and the modified ratio of activated to resting TIICs being the most consistent features distinguishing smokers and never-smokers across different cancers, with both being correlated with survival outcomes. Analysis of existing single-cell RNA-seq data further showed that smoking differentially affects the gene expression profile of cancer patients based on the immune cell type. The smoking-induced changes in the patterns of immune cells and their correlations to survival outcomes are stronger in female smokers.

cancer biology↗