Biology subjects

Langley, R. J.

Publications and source records attributed to Langley, R. J..

4 recordsLinked to original sources

bioRxiv2026

What Makes a Good Vaccine Antigen Target? Defining Key Features and Predicting Candidates in the Staphylococcus aureus Proteome

The rapid advancement of computational methods is transforming vaccine development by enabling faster, data-driven identification of promising antigens. In this study, we applied an in-silico pipeline to assess a broad set of sequence, structure, localisation, and immunology-derived features and determine which most effectively discriminate antigens from non-antigens in bacteria. Using these insights, we identified bacterial proteins with high potential as vaccine antigens. Applied to Staphylococcus aureus, this approach prioritized 304 candidate antigens, highlighting SSLs, nutrient acquisition factors, and cell wall-associated enzymes. While these findings demonstrate the potential of bioinformatics-guided antigen discovery, experimental validation remains essential. This work underscores the growing role of integrated computational and machine-learning approaches in accelerating next-generation vaccine design.

bioinformatics↗

bioRxiv2026

HIV-1 interactions with sialic acid-binding bacterial lectins promote virus infectivity in vitro and mucosal transmission in humanized mice

Most HIV-1 transmission occurs at mucosal surfaces, which are colonized by the host microbiota. However, interactions between HIV and bacteria or bacterial products derived from the human microbiome are poorly characterized, and their biological consequences are largely unexplored. Here, we evaluated the effects of sialic acid-binding lectins expressed by bacterial species ubiquitous in the human microbiota on HIV-1 infectivity using viruses produced in 293T cells and human primary cells. We demonstrated that these bacterial lectins enhanced HIV-1 infectivity in a sialoglycan-dependent manner. Specifically, Siglec-like binding region lectins (SLBR-N, SLBR-H, and SLBR-B) from Streptococcus gordonii and Staphylococcal superantigen-like lectins (SSL3, SSL4, and SSL11) from Staphylococcus aureus increased HIV-1 infectivity to varying extents, depending on lectin type and virus strain. Among these lectins, SLBR-N exhibited the greatest potency, corresponding with its superior ability to bind virions and promote virus-cell attachment. This enhancing activity was observed for direct infection of TZM-bl reporter cells and primary CD4+ T cells, as well as trans-infection in the presence or absence of the mannose-binding host lectin DC-SIGN. Importantly, these findings were corroborated in vivo using humanized mice, in which pre-exposure to SLBR-N promoted rectal HIV-1 transmission and increased viral burdens in plasma and splenic cells. Collectively, the data show sialoglycan-binding bacterial lectins as microbial factors that can enhance HIV-1 transmission at mucosal surfaces, highlighting a potential direct role for the microbiota in modulating HIV-1 acquisition risk. Author SummaryHIV is commonly transmitted from one person to another across mucosal surfaces, such as those lining the genital and rectal tracts, which are densely populated by bacteria that make up the human microbiota. Yet, surprisingly little is known about how these bacteria and the molecules they produce influence HIV infection. In this study, we investigated a group of bacterial proteins known as sialic acid-binding lectins that are expressed by common members of the human microbiome: Siglec-like binding region lectins from Streptococcus gordonii and superantigen-like lectins from Staphylococcus aureus. Using multiple HIV strains and several types of target cells, we demonstrate that lectin binding to HIV can increase virus attachment to target cells and thereby enhance infection, although the magnitude of this effect varies among lectins and virus strains. Lectin binding also facilitates HIV spread from cell to cell and promotes mucosal HIV infection in a humanized mouse model, resulting in a higher viral burden in the blood and tissues. These findings identify bacterial lectins as important factors that can influence HIV infection and implicate a potential role for the human microbiota in determining susceptibility to HIV infection.

microbiology↗

bioRxiv2025

Analysis of alternative splicing uncovers a vastly expanded transcriptomic response to hypoxia in human vascular endothelial cells

Hypoxia is a fundamental pathophysiological stimulus that plays important roles in multiple cardiopulmonary diseases. During hypoxic stress, cells adapt by undergoing widespread transcriptional reprogramming. The conventional approach to investigating this response has largely involved RNA-seq analysis which typically quantifies transcriptional output at the level of individual genes. However, as most mammalian genes encode multiple transcripts that are divergently regulated by alternative splicing, consolidating these discrete features to the gene level can obscure critical changes within the transcriptome that are largely unappreciated. To more accurately define the role of individual transcript usage during hypoxia, herein we employed three different analytical strategies that collectively identified thousands of instances of alternative splicing in human endothelial cells undergoing hypoxic stress. Notably, the set of differentially utilized transcripts displayed minimal overlap with the genes identified to be differentially expressed by conventional RNA-seq analysis, indicating divergent usage of individual transcripts does not reliably culminate in a detectable change in overall expression. This outcome is particularly clear at the earliest time-point of hypoxia where we found the transcriptional response was mediated almost exclusively by alternative splicing. A subset of these acutely responsive genes was variably detected as differentially expressed or alternatively spliced at later time points, demonstrating hypoxic transcription is highly dynamic and temporally complex. Further, the number of genes in pathways incriminated in the hypoxic response was also expanded considerably when alternatively spliced transcripts were included in the analysis, suggesting distinct attributes of the hypoxic transcriptome are unveiled by transcript level assays that would otherwise be obfuscated by standard RNA-seq analyses that summarize expression to the gene level. Collectively, these results strongly point to alternative splicing being a significant, albeit understudied, component of the transcriptional response to hypoxic stress which is vastly more complicated than previously thought.

genomics↗

bioRxiv2016

Mortality prediction in sepsis via gene expression analysis: a community approach

Improved risk stratification and prognosis in sepsis is a critical unmet need. Clinical severity scores and available assays such as blood lactate reflect global illness severity with suboptimal performance, and do not specifically reveal the underlying dysregulation of sepsis. Here three scientific groups were invited to independently generate prognostic models for 30-day mortality using 12 discovery cohorts (N=650) containing transcriptomic data collected from primarily community-onset sepsis patients. Predictive performance was validated in 5 cohorts of community-onset sepsis patients (N=189) in which the models showed summary AUROCs ranging from 0.765-0.89. Similar performance was observed in 4 cohorts of hospital-acquired sepsis (N=282). Combining the new gene-expression-based prognostic models with prior clinical severity scores led to significant improvement in prediction of 30-day mortality (p<0.01). These models provide an opportunity to develop molecular bedside tests that may improve risk stratification and mortality prediction in patients with sepsis, improving both resource allocation and prognostic enrichment in clinical trials.

bioinformatics↗