Search bioRxiv⌕ Search

Biology subjects

Diallo, I.

Publications and source records attributed to Diallo, I..

4 recordsLinked to original sources

A cell surface proteomic atlas reveals socioeconomic status associated immune diversity

Socioeconomic status (SES) is a potent determinant of immune variation, yet unbiased approaches to holistically map the effect of SES on the immune system are lacking. We developed a high-dimensional flow cytometry-based profiling approach to analyse 331 cell surface proteins across 33 immune cell subsets within an SES-stratified Senegalese cohort, alongside a European cohort (Netherlands). We identified 108 SES-related markers across the immune system, revealing that lower SES individuals exhibited downregulation of surface proteins, affecting in particular adhesins, chemokine and complement receptors. Conversely, lower SES was associated with hallmarks of chronic activation and exhaustion including upregulation of immune checkpoints. Metabolic profiling demonstrated that while lower SES individuals displayed elevated baseline RNA transcription, higher SES individuals exhibited superior protein translation rates. We validated these SES-related immune trends in an independent cohort and provide an interactive online resource for exploring this surface protein atlas on immune cell subsets. Taken together, these findings provide a global overview of how the cell surface proteome varies by SES, and identify molecular changes that can affect vaccine efficacy and disease outcomes.

immunology↗

Mass cytometry data integration methods reveal rural-urban gradient of immune profiles across geography

The human immune system strongly varies across populations and is shaped by a wide range of host and environmental factors. As such, a rural compared to urban lifestyle has previously been associated with baseline differences in immune profiles, which can impact outcome of vaccination. The question whether there is a immune signature that associates with rural living irrespective of ancestry or geography has been addressed here along with which analytical methods are most suitable. Using three mass cytometry datasets, we studied shared and population-specific immune characteristics of healthy rural- or urban-living Indonesian, Senegalese and Tanzanian adults and urban-living Europeans. After harmonized preprocessing and quality control, 75.4 million cells were integrated using four different data-integration methods. Among these, CytoNorm with in silico references performed best, revealing shared differences in the differentiation state within the lymphocyte compartment that distinguishes rural from urban-living individuals. Differentiated CD4+ T cells expressing CTLA-4, PD-1 and ICOS characterized rural living, as did CD4+ T cells with high CD161 expression in combination with CRTH2 and GATA3. In the innate compartment, CD56- CD16 NK cells with low CD38 and CD11c expression were expanded in rural living subjects. Together, our results demonstrate that, using a harmonized analytical pipeline and machine learning-based integration, large-scale mass cytometry data can be combined across diverse cohorts to identify shared immunological hallmarks of rural living. These signatures may provide targets for modulating immune responses in future vaccine studies.

immunology↗

Novel Hendra virus variant detected by sentinel surveillance of Australian horses.

A novel Hendra virus (HeV) variant, not detected by routine testing, was identified and isolated from a Queensland horse that suffered acute, fatal disease consistent with HeV infection. Whole genome sequencing and phylogenetic analysis demonstrated the variant to have ~83% nucleotide identity to the prototype HeV strain. An updated RT-qPCR assay was designed for routine HeV surveillance. In silico and in vitro comparison of the receptor-binding protein with prototypic HeV showed that the human monoclonal antibody m102.4 used for post-exposure prophylaxis, as well as the current equine vaccine, should be effective against this variant. Genetic similarity of this virus to sequences detected from grey-headed flying-foxes suggests the variant circulates at-least in this species. Studies determining infection kinetics, pathogenicity, reservoir-species associations, viral-host co-evolution and spillover dynamics for this virus are urgently needed. Surveillance and biosecurity practices should be updated to appreciate HeV spillover risk across all regions frequented by flying foxes.

molecular biology↗

Population history and genetic adaptation of the Fulani nomads: Inferences from genome-wide data and the lactase persistence trait

Human population history in the Holocene was profoundly impacted by changes in lifestyle following the invention and adoption of food-production practices. These changes triggered significant increases in population sizes and expansions over large distances. Here we investigate the population history of the Fulani, a pastoral population extending throughout the African Sahel/Savannah belt. Based on genome-wide analyses we propose that ancestors of the Fulani population experienced admixture between a West African group and a group carrying both European and North African ancestries. This admixture was likely coupled with newly adopted herding practices, as it resulted in signatures of genetic adaptation in contemporary Fulani genomes, including the control element of the LCT gene enabling carriers to digest lactose throughout their lives. The lactase persistence (LP) trait in the Fulani is conferred by the presence of the allele T-13910, which is also present at high frequencies in Europe. We establish that the T-13910 LP allele in Fulani individuals analysed in this study lies on a European haplotype background thus excluding parallel convergent evolution. Our findings further suggest that Eurasian admixture and the European LP allele was introduced into the Fulani through contact with a North African population/s. We furthermore confirm the link between the lactose digestion phenotype in the Fulani to the MCM6/LCT locus by reporting the first Genome Wide Association study (GWAS) of the lactase persistence trait. We also further explored signals of recent adaptation in the Fulani and identified additional candidates for selection to adapt to herding life-styles.

evolutionary biology↗