Biology subjects

Rajagopala, S. V.

Publications and source records attributed to Rajagopala, S. V..

3 recordsLinked to original sources

bioRxiv2026

Esophageal epithelial cell-state transitions underlie the severity of pediatric eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a leading cause of chronic esophageal dysfunction driven by immune-mediated inflammation. Peak eosinophil count (PEC) in esophageal biopsies is routinely used to assess disease activity, and its associated molecular mechanisms have been well studied. However, PEC only partially captures overall disease severity, which is comprehensively captured by the Index of Severity for Eosinophilic Esophagitis (I-SEE). In contrast to PEC, the molecular and cellular programs associated with the I-SEE-defined disease severity, particularly in children, remain poorly understood. We integrated bulk transcriptomic profiling of pediatric esophageal biopsies with clinical severity metrics and a matched single-cell transcriptomic reference. Increasing severity was associated with a shift from type 2 inflammatory activation toward epithelial stress, cytoskeletal and junctional disruption, metabolic dysfunction, and extracellular matrix remodeling. Single-cell-informed analyses identified that proliferating and transitional epithelial cell states were strongly associated with higher I-SEE scores and exhibited impaired differentiation, heightened metabolic and oxidative stress responses, and structural remodeling programs not captured by bulk transcriptomic analyses alone. These findings reposition epithelial remodeling, rather than eosinophil burden alone, as a central molecular correlate of disease severity in pediatric EoE and provide a framework for improved disease stratification and therapeutic intervention.

immunology↗

bioRxiv2026

Biological signatures of history: Examination of composite biomes and Y chromosome analysis from da Vinci-associated cultural artifacts

Cultural heritage objects can accumulate DNA from materials, environments, and repeated human contact, but biomolecular profiling of such items is constrained by nondestructive sampling requirements, ultra-low biomass, and high contamination risk. Here we present a minimally invasive workflow that integrates gentle swab collection, low- input whole-metagenome sequencing, taxonomic profiling, and Y-chromosome analyses to recover "biological signatures of history" from Renaissance-era artwork and archival correspondence associated with ancestors of Leonardo da Vinci. Across artifacts, we recovered heterogeneous mixtures of microbial and eukaryotic DNA (including bacteria, fungi, plants, and viruses) consistent with composite "biomes" that reflect differences in substrate, storage, conservation treatments, and handling. Multivariate comparisons show reproducible sample-to-sample separations. In parallel, we assessed human Y-chromosome signal using a panel of [~]90,000 phylogenetically informative markers and partial Y-STR profiling where feasible. Across multiple independent swabs from Leonardo da Vinci-associated items, the obtained Y chromosome marker data suggested assignments withing the broader E1b1/E1b1b clade. However, the control samples also indicate mixed contributions consistent with modern handling and other sources. Together, these data demonstrate the feasibility as well as limitations of combining metagenomics and human DNA marker analysis for cultural heritage science, providing a baseline workflow for future conservation science studies and hypothesis-driven investigations of provenance, authentication and handling history.

genomics↗

bioRxiv2022

Mucosal gene expression in response to SARS-CoV-2 is associated with early viral load.

Little is known about the relationships between symptomatic early-time SARS-CoV-2 viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate COVID-19. We measured SARS-CoV-2 viral load using qRT-PCR. We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 85% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited co-detection of common respiratory viruses i.e., only the human Rhinovirus (HRV) being identified in 6% of the samples. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusted for age, sex and race. Interestingly, the expression levels of most of these genes plateaued at a CT value of ~25. Overall, our data shows that early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, which potentially could modify COVID-19 outcomes. AUTHOR SUMMARYSeveral prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load and airway mucosal gene expression and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during Spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load with interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load-dependent and may modify COVID-19 outcomes.

genomics↗