Biology subjects

Ghimire, D.

Publications and source records attributed to Ghimire, D..

4 recordsLinked to original sources

bioRxiv2026

Capturing Spatial Heterogeneity Using UAV-Derived Multispectral Phenotypes and Random Regression Models Improves Genetic Evaluation in Alfalfa Breeding Trials

Spatial heterogeneity is a major source of environmental noise in field trials, reducing genetic evaluation accuracy. Conventional spatial correction methods use field layout and plot proximity but often fail to capture in-season dynamics or leverage temporal data from high-throughput phenotyping. We hypothesized that longitudinal UAV-derived multispectral measurements could characterize field-scale environmental heterogeneity and improve genetic evaluation in breeding trials. Multispectral imagery was collected throughout the growing season across eight alfalfa trials in New York and New Mexico (20222023). Vegetation indices were evaluated for heritability and association with biomass yield using univariate and multi-trait models. Longitudinal measurements were modeled with random regression (RR) to estimate plot-specific permanent environmental effects (PEE), incorporated into genomic mixed models within a two-stage framework. Model performance was compared with conventional autoregressive (AR) and baseline (no correction) models using metrics of consistency and accuracy of estimated genetic effects across replicates. Vegetation indices showed moderate to high heritability, with GNDVI consistently outperforming NDVI and NDRE. Both univariate and multi-trait analyses revealed substantial spatial variability, particularly in New Mexico trials. RR-derived PEE captured field-scale spatial patterns and improved genetic signal recovery relative to baseline and AR models, with the largest gains under strong spatial heterogeneity and comparable performance where variability was limited. The RR framework improved reproducibility of genetic effect estimates across independent field subsets without compromising agreement with full-trial evaluations. These findings show that integrating UAV data via random regression enhances genetic signal recovery and selection accuracy, with broader potential for precision agriculture and biosensor-driven crop management.

genetics↗

bioRxiv2026

Post-infection immune response in adults with COVID-19 with and without nirmatrelvir-ritonavir treatment and virologic rebound

BackgroundNirmatrelvir-ritonavir (N-R) reduces morbidity and mortality from COVID-19 in high-risk individuals; however, N-R use has been associated with risk of SARS-CoV-2 virologic rebound. The mechanisms contributing to virologic rebound after N-R treatment are currently unknown. One plausible mechanism is that antiviral treatment may alter the development of immune responses to SARS-CoV-2 infection, thereby contributing to rebound after cessation of therapy. MethodsWe profiled immune responses in a case-ascertained, longitudinal, prospective cohort of ambulatory individuals with COVID-19. Participants were grouped according to whether virological rebound occurred and whether they had received N-R treatment. We assessed antibody, T-cell, and innate responses. ResultsWe observed no differences in the binding or neutralizing antibody, T-cell, and innate immune responses between participants with virologic rebound compared to participants without virologic rebound. N-R use was associated with slightly weaker antibody responses overall, even after adjustment for immunosuppression. ConclusionVirologic rebound after N-R treatment is likely driven by non-immune mechanisms. FundingThe project was supported by the National Institutes of Health (R01 AI 138801) and the Massachusetts Consortium on Pathogen Readiness. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

immunology↗

bioRxiv2026

Subtype-specific differences in susceptibility to monoclonal antibodies and vaccines among contemporary RSV-A and RSV-B isolates

Respiratory syncytial virus (RSV) continues to circulate at high levels despite the introduction of new monoclonal antibodies (mAbs) and vaccines targeting the prefusion F (pre-F) protein. We analyzed the viral genome sequences of 133 RSV clinical samples collected during the 2022-2023 and 2023-2024 seasons, and selected representative isolates for phenotypic testing. We selected four RSV A and four RSV B replication-competent, sequence-verified stocks that were assessed for replication kinetics in vitro and neutralization sensitivity by a panel of F-targeting mAbs and polyclonal sera using a rabbit vaccination model. Isolates retained sensitivity to all mAbs tested. We detected no mutations in mAb binding sites in the isolates tested. RSV-A isolates were slightly less susceptible to multiple mAbs than RSV-B isolates. Antigenic cartography revealed a separation of antibody responses by subtype: RSV-A isolates clustered together and aligned with lower neutralization by antibodies such as MPE8 and 101F, whereas RSV-B isolates formed a distinct cluster associated with higher mAb susceptibility. In a rabbit vaccination model, RSV-A-only sera efficiently neutralized all RSV-A isolates and the RSV-B1 reference strain but showed diminished activity against contemporary RSV-B isolates. RSV-B-only sera displayed balanced neutralization across both subtypes. Combined RSV-A+B immunization produced uniformly strong responses to all isolates, suggesting that multivalent exposure may overcome subtype-specific antibody polarization. Collectively, our results demonstrate consistent antigenic divergence of RSV subtypes and underscore the importance of considering genetic and phenotypic divergence for F-directed immunoprophylaxis. ImportanceRSV remains a major cause of lower respiratory tract infections. Although new mAbs and vaccines have been approved in recent years, the impact of circulating genetic diversity on these therapeutics is incompletely understood. In this study, we demonstrate how recent RSV isolates respond to a panel of mAbs and whether sera from rabbits vaccinated with mRNA vaccines effectively neutralize these isolates. We reveal that RSV-A isolates are more resistant to neutralization by mAbs than RSV-B isolates, and the bivalent vaccine elicits broader neutralizing responses than the monovalent vaccine. This study provides insights into how viral diversity may influence antibody-mediated protection and suggests that recent RSV-B isolates may respond differently from the laboratory-adapted strains commonly used in research.

microbiology↗

bioRxiv2023

An intact amber-free HIV-1 system for in-virus protein bioorthogonal click labeling that delineates envelope conformational dynamics

The HIV-1 envelope (Env) glycoprotein is conformationally dynamic and mediates membrane fusion required for cell entry. Single-molecule fluorescence resonance energy transfer (smFRET) of Env using peptide tags has provided mechanistic insights into the dynamics of Env conformations. Nevertheless, using peptide tags risks potential effects on structural integrity. Here, we aim to establish minimally invasive smFRET systems of Env on the virus by combining genetic code expansion and bioorthogonal click chemistry. Amber stop-codon suppression allows site-specifically incorporating noncanonical/unnatural amino acids (ncAAs) at introduced amber sites into proteins. However, ncAA incorporation into Env (or other HIV-1 proteins) in the virus context has been challenging due to low copies of Env on virions and incomplete amber suppression in mammalian cells. Here, we developed an intact amber-free virus system that overcomes impediments from preexisting ambers in HIV-1. Using this system, we successfully incorporated dual ncAAs at amber-introduced sites into Env on intact virions. Dual-ncAA incorporated Env retained similar neutralization sensitivities to neutralizing antibodies as wildtype. smFRET of click-labeled Env on intact amber-free virions recapitulated conformational profiles of Env. The amber-free HIV-1 infectious system also permits in-virus protein bioorthogonal labeling, compatible with various advanced microscopic studies of virus entry, trafficking, and egress in living cells. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/530526v1_ufig1.gif" ALT="Figure 1000"> View larger version (30K): org.highwire.dtl.DTLVardef@10e7728org.highwire.dtl.DTLVardef@b1078aorg.highwire.dtl.DTLVardef@65f874org.highwire.dtl.DTLVardef@9ab0e8_HPS_FORMAT_FIGEXP M_FIG C_FIG Amber-free HIV-1 infectious systems actualized minimal invasive Env tagging for smFRET, versatile for in-virus bioorthogonal click labeling in advanced microscopic studies of virus-host interactions.

microbiology↗