Biology subjects

Khan, A. K.

Publications and source records attributed to Khan, A. K..

3 recordsLinked to original sources

bioRxiv2024

Gut Microbiome Signatures During Acute Infection Predict Long COVID

Long COVID (LC), manifests in 10-30% of non-hospitalized individuals post-SARS-CoV-2 infection leading to significant morbidity. The predictive role of gut microbiome composition during acute infection in the development of LC is not well understood, partly due to the heterogeneous nature of disease. We conducted a longitudinal study of 799 outpatients tested for SARS-CoV-2 (380 positive, 419 negative) and found that individuals who later developed LC harbored distinct gut microbiome compositions during acute infection, compared with both SARS-CoV-2-positive individuals who did not develop LC and negative controls with similar symptomatology. However, the temporal changes in gut microbiome composition between the infectious (0-1 month) and post-infectious (1-2 months) phases was not different between study groups. Using machine learning, we showed that microbiome composition alone more accurately predicted LC than clinical variables. Including clinical data only marginally enhanced this prediction, suggesting that microbiome profiles during acute infection may reflect underlying health status and immune responses thus, help predicting individuals at risk for LC. Finally, we identified four LC symptom clusters, with gastrointestinal and fatigue-only groups most strongly linked to gut microbiome alterations.

genomics↗

bioRxiv2024

A unified Bayesian approach to transcriptome-wide association study

The transcriptome-wide association study (TWAS) has identified novel gene-trait associations, providing essential biological insights. TWAS combines reference panel transcriptome and genome-wide association study (GWAS) data. Traditional TWAS methods construct a prediction model for gene expression based on the transcriptome data, which is then employed to impute gene expression in the GWAS data. The complex trait in GWAS is regressed on the predicted expression to identify gene-trait associations. Such a two-step approach ignores the uncertainty of the imputed expression and can lead to reduced inference accuracy. We develop a unified Bayesian approach for TWAS that avoids the need for a two-step approach by modeling the two datasets simultaneously. We consider the horseshoe prior to model the relationship between gene expression and local SNPs, and the spike and slab prior to test for an association between the genetic component of expression and the trait to build an integrated Bayesian framework. We extend the method to conducting a multi-ancestry TWAS, focusing on discovering genes that affect the trait in either or both ancestries. Using extensive simulations, we demonstrate that the new approach performs better than existing methods in terms of correctly classifying non-null genes and the accuracy of effect size estimation. To demonstrate our approach, we perform a single and multi-ancestry TWAS for intraocular pressure (IOP), integrating the Geuvadis transcriptome and UK Biobank GWAS data. We find that the identified set of IOP-associated genes is enriched in relevant pathways.

genomics↗

bioRxiv2021

Next generation vaccine platform: polymersomes as stable nanocarriers for a highly immunogenic and durable SARS-CoV-2 spike protein subunit vaccine

Multiple successful vaccines against SARS-CoV-2 are urgently needed to address the ongoing Covid-19 pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein co-administered with CpG adjuvant. To enhance the immunogenicity of our formulation, both antigen and adjuvant were encapsulated with our proprietary artificial cell membrane (ACM) polymersome technology. Structurally, ACM polymersomes are self-assembling nanoscale vesicles made up of an amphiphilic block copolymer comprising of polybutadiene-b-polyethylene glycol and a cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane. Functionally, ACM polymersomes serve as delivery vehicles that are efficiently taken up by dendritic cells, which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of memory CD4+ and CD8+ T cells that produce Th1 cytokines. This study is an important step towards the development of an efficacious vaccine in humans.

immunology↗