Biology subjects

Rodriguez, J.

Publications and source records attributed to Rodriguez, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

An Intrinsic-hoc Framework for Heterogeneous Cellular Senescence Elucidation Using Deep Graph Representation Learning and Experimental Validation

Cellular senescence is a primordial driver of tissue and organ aging, and the accumulation of senescent cells (SnCs) has been implicated in numerous age-related diseases. A major barrier to studying senescence is the rarity and heterogeneity of SnCs, which are not a uniform population but instead comprise diverse senotypes shaped by cell-of-origin and microenvironmental context. Such heterogeneity exceeds what classical senescence hallmarks can resolve at single-cell resolution, motivating the need for computational frameworks that can capture senotype-level diversity intrinsically. Here, we introduce DeepSAS, a deep graph representation learning framework that robustly identifies cell-type-specific SnCs and their senescence-associated genes (SnGs). DeepSAS incorporates a heterogeneous graph that integrates intracellular transcriptional states with intercellular communication cues, enabling the joint inference of senescent cells and senescence-linked genes through attention-based contrastive learning. Applied to public healthy eye and lung atlases, DeepSAS identified SnCs whose proportions positively correlate with aging. From in-house idiopathic pulmonary fibrosis (IPF) patient scRNA-seq data, DeepSAS detected 1,678 SnCs (out of 24,125 cells) and 263 SnGs across 26 cell types, including 43 SnGs that are uniquely associated with a single cell type. We generated high-resolution Xenium spatial transcriptomics data to further validate SnGs in IPF, revealing NFE2L2 as a SnG specifically enriched in CTHRC1+ fibroblasts. Notably, the ex vivo bleomycin-induced senescence in human precision-cut lung slice (hPCLS) samples similarly identified NFE2L2 as an SnG in CTHRC1+ fibroblasts, albeit with stronger transcriptional signals, suggesting mechanistic differences in senescence cells associated with chronic and acute injury. Overall, DeepSAS uncovers distinct senescence programs and infers cell-type-specific SnGs that are difficult to resolve using existing marker-based approaches. We believe it offers a generalizable and translationally relevant strategy for advancing senescence biology and therapeutic development.

bioinformatics↗

bioRxiv2025

The C. elegans gustatory receptor homolog LITE-1 is a chemoreceptor required for diacetyl avoidance

The nematode C. elegans does not have eyes but can respond to aversive UV and blue light stimulation and even distinguish colours. The gustatory receptor homolog LITE-1 was identified in forward genetic screens for worms that failed to respond to blue light stimulation. When LITE-1 is expressed in body-wall muscles, it causes contraction in response to blue light suggesting that LITE-1 is both necessary and sufficient for blue light response. Here we show that in addition to light avoidance, LITE-1 is also required for worms avoidance of high concentrations of diacetyl, an odorant that is attractive at low concentrations. Like blue light, diacetyl causes muscle contraction in transgenic worms engineered to express LITE-1 in body-wall muscles. These data are consistent with a direct chemoreceptor function for LITE-1 which would make it a multimodal sensor of aversive stimuli.

neuroscience↗

bioRxiv2025

Leaf shape modulates climate trait relationships in the wild species Chenopodium hircinum (Amaranthaceae)

Understanding how leaf morphology mediates plant responses to environmental variation is essential for predicting species adaptability under climate change. In this study, we investigated natural variation in leaf shape and associated functional- physiological traits (FPTs) across populations of Chenopodium hircinum grown in a common garden. We found that leaf shape strongly correlates with the climatic conditions of population provenance, while functional and physiological traits are independently associated with morphology rather than directly with climate. Landmark-based morphometric analysis revealed that the second principal component, distinguishing deeply lobed from rounded leaves, is significantly linked to key traits such as leaf mass per unit area (LMA) and stomatal conductance. These relationships suggest that morphology mediates a functional continuum between resource-use strategies. Notably, within-population phenotypic variation accounted for much of the observed trait diversity, underscoring the role of individual-level phenotypic plasticity in shaping ecological function. Our results challenge traditional views on the thermoregulatory role of leaf lobation and highlight morphology as a central axis of adaptation. This work advances understanding of trait integration in response to environmental heterogeneity and suggests that plasticity in leaf shape and function may enhance resilience of C. hircinum across its native range.

plant biology↗

bioRxiv2025

Archaeal SegAB forms a bipolar structure that promotes chromosome segregation in spherical cells

Archaeal segAB operons are thought to promote chromosome segregation, but their mechanism remains unknown. We employ comparative genomics, structural biology, genetic knockouts, and quantitative cell biology to investigate how SegA and SegB proteins work together to segregate chromosomes in the thermophilic archaeon Sulfolobus acidocaldarius. In vitro, SegB binds a centromeric DNA sequence adjacent to the segAB operon, and in vivo forms a distinct focus on each segregating chromosome. SegA, a ParA-like ATPase, binds DNA non-specifically in vitro and promotes chromosome compaction and segregation in vivo. During division, SegA shifts from chromosome-associated puncta to form a single, elongated figure that runs between separating SegB foci. Late in division, SegA retreats to regions surrounding separated SegB foci. Elongated SegA figures appear in segB knockout cells but no longer lie perpendicular to the division plane. We propose that SegA and SegB interact to form a bipolar, DNA-segregating structure radically different from bacterial ParABS systems.

cell biology↗

bioRxiv2025

Proteostasis control via HSP90α sustains YAP activity to drive aggressive behaviours in cancer-associated fibroblasts

Cancers adapt proteostasis to cope with the burden of misfolded proteins, stabilize key signalling nodes and sustain their malignant behaviour. Tumour stroma is subjected to similar stresses, but how they influence its aberrant status remains unclear. We show that tumour stroma presents consistent upregulation of target genes associated to the major misfolding regulator HSP90 in cancer-associated fibroblasts (CAFs), and that HSP90 is required for CAFs to remodel the extracellular matrix (ECM) and promote cancer cell motility and growth. Mechanistically, HSP90 sustains TGF{beta} responses and YAP protein levels required for CAF functionality. In vivo, stromal or fibroblast-specific loss of HSP90 results in reduced ECM deposition, angiogenesis, growth and dissemination of breast tumours. Clinical analyses reveal a correlation between HSP90-dependent programs and YAP activity in CAFs, that are also associated with poor patient prognosis. Our findings uncover a link between proteostasis, mechanotransduction and generation of aggressive tumour microenvironments through HSP90.

cancer biology↗

bioRxiv2025

Jack of all trades and master of most: Carpobrotus taxa show no trade-off in reproductive strategies

O_LIThe ability to reproduce via multiple strategies is crucial for the invasion success of alien plant species. Here, we use Carpobrotus taxa (species and hybrids) to explore how trade-offs between and within these strategies may influence plant invasion dynamics. Native to South Africa, Carpobrotus plants are globally prominent in coastal ecosystems, reproducing by seed and clonally, and frequently hybridizing in both native and introduced regions. Three genetically distinct clusters were previously identified, with evidence of hybridization within and between these clusters in native and non-native ranges. C_LIO_LIWe collected fruit samples from populations representing the genetic clusters and their hybrids across native and non-native ranges (i.e., Europe, California, and New Zealand). These genetic clusters reflect the complex taxonomy of Carpobrotus, where species boundaries are unclear due to hybridization and morphological similarity. We then assessed seed set, seed mass, germination rates, and early growth under varying abiotic conditions alongside genetic estimates of clonality. C_LIO_LIGermination rates were influenced by temperature, moisture, and nutrient levels. Non-native populations demonstrated higher seed set, seed mass, and germination success compared to native populations, indicating a stronger investment in sexual reproduction. These populations also showed higher levels of clonality, shown by lower genotypic richness, suggesting that both reproductive strategies enhance invasive potential. C_LIO_LIHigh-clonality populations produced more seeds, demonstrating that the two reproductive strategies are not mutually exclusive. These results highlight the importance of multiple reproductive strategies for the establishment and spread of Carpobrotus taxa and provide insights into the mechanisms driving their global success. C_LI

plant biology↗

bioRxiv2024

An improved neural network model enables worm tracking in challenging conditions and increases signal-to-noise ratio in phenotypic screens

High-resolution posture tracking of C. elegans has applications in genetics, neuroscience, and drug screening. While classic methods can reliably track isolated worms on uniform backgrounds, they fail when worms overlap, coil, or move in complex environments. Model-based tracking and deep learning approaches have addressed these issues to an extent, but there is still significant room for improvement in tracking crawling worms. Here we train a version of the DeepTangle algorithm developed for swimming worms using a combination of data derived from Tierpsy tracker and hand-annotated data for more difficult cases. DeepTangleCrawl (DTC) outperforms existing methods, reducing failure rates and producing more continuous, gap-free worm trajectories that are less likely to be interrupted by collisions between worms or self-intersecting postures (coils). We show that DTC enables the analysis of previously inaccessible behaviours and increases the signal-to-noise ratio in phenotypic screens, even for data that was specifically collected to be compatible with legacy trackers including low worm density and thin bacterial lawns. DTC broadens the applicability of high-throughput worm imaging to more complex behaviours that involve worm-worm interactions and more naturalistic environments including thicker bacterial lawns.

animal behavior and cognition↗

bioRxiv2024

Electroconvulsive therapy generates a hidden wave after seizure

Electroconvulsive therapy (ECT) is a fast-acting, highly effective, and safe treatment for medication-resistant depression. Historically, the clinical benefits of ECT have been attributed to generating a controlled seizure; however, the underlying neurobiology is understudied and unresolved. Using optical neuroimaging of neural activity and hemodynamics in a mouse model of ECT, we demonstrated that a second brain event follows seizure: cortical spreading depolarization (CSD). We found that ECT pulse parameters and electrode configuration directly shaped the wave dynamics of seizure and subsequent CSD. To translate these findings to human patients, we used non-invasive diffuse optical monitoring of cerebral blood flow and oxygenation during routine ECT treatments. We observed that human brains reliably generate hyperemic waves after ECT seizure which are highly consistent with CSD. These results challenge a long-held assumption that seizure is the primary outcome of ECT and point to new opportunities for optimizing ECT stimulation parameters and treatment outcomes.

neuroscience↗

bioRxiv2024

LEAF SHAPE OF QUINOA WILD ANCESTOR CHENOPODIUM HIRCINUM IN A GEOGRAPHIC CONTEXT

PremiseIntraspecific variation in plant traits, such as leaf morphology, offers insights into local adaptation and the ecological niche breadth of species. Chenopodium hircinum, the wild ancestor of quinoa, is widely distributed across various ecoregions in Argentina. A detailed comparative analysis of leaf morphology across 23 populations covering its entire distribution was conducted to understand patterns of intraspecific variation along geographic gradients. Materials and MethodsUsing 104 leaves from these populations, leaf shapes were described through shape, landmarks, and Fourier descriptors. Both univariate and multivariate analyses were employed to evaluate variations among and within populations and to link leaf shape patterns with climatic and geographical variables at the sites of origin. ResultsA significant variability in leaf shapes was found across all ecoregions, with marked integration among populations. While landmark-based and Fourier analyses differentiated populations, shape descriptors introduced complexity in identification. Leaf morphology varied widely, from rounded and toothed to sharply lobed, with prominent lobes located at the base or middle of the leaf. The key environmental factors influencing leaf shape, particularly lobulation and relative positioning, were mean annual temperature and altitude. ConclusionsThe findings suggest that in C. hircinum, leaf shape variability goes beyond the simple lobed vs. entire dichotomy and is shaped by environmental temperatures. Leaf morphology and margin traits are primarily governed by the relative position of the lobes, which are strongly correlated with the mean temperature at the populations origin. This convergence across different ecoregions highlights the need for further research to explore the functional significance of such variation.

plant biology↗

bioRxiv2024

A reaction norm for flowering time plasticity reveals physiological footprints of maize adaptation

Understanding how plant phenotypes are shaped by their environments is crucial for addressing questions about crop adaptation to new environments. This study focused on analyzing the genetic variability underlying genotype-by-environment interactions and adaptation for flowering time in maize. We present a physiological reaction norm for flowering time plasticity (PRN-FTP), modeled from multi-environment trial networks and decomposed into its physiological components. We show how genotype-specific differences in developmental responses to temperature fluctuations condition differences in photoperiod perceived among genotypes. This occurs not only across but also within common environments, as the perception of photoperiod is altered by variation in rates of development and durations for becoming sensitized to photoperiod. Using a new metric for envirotyping sensed photoperiods for maize, it was found that, at high latitudes, different genotypes in the same environment can experience up to hours-long differences in photoperiod. This emphasizes the importance of considering genotype-specific differences in the experienced environment when investigating plasticity. Modeling the PRN-FTP for globally representative breeding material showed that tropical and temperate germplasm occupy distinct territories of the trait space for PRN-FTP parameters. Placed in the historical context of maize, our findings suggest that the geographical spread and breeding of maize was mediated by a specific modality of ecophysiological adaptation of flowering time. Our study has implications for understanding crop adaptation and for future crop improvement efforts. Article SummaryMaize adjusts its flowering time across environments using genetic pathways tuned to cues like temperature and day length. This study models how different varieties perceive and respond to these factors, revealing that genotypes can perceive the same environment in distinct ways. By disentangling the ecophysiological basis of genotype-environment interactions, the research explores maize diversity and highlights how adaptation and breeding have shaped distinct strategies for flowering time regulation in tropical and temperate varieties.

plant biology↗

bioRxiv2024

Prioritizing Metabolic Gene Regulators through Multi-Omic Network Integration in Maize

Gene regulatory networks (GRNs) link transcription factors (TFs) to the biological processes they control. Assembling them remains difficult because the relevant data types (gene expression, protein-DNA interactions, and genetic variation) are large, heterogeneous, and rarely combined. Here, we developed and benchmarked a framework that integrates these data into TF-function predictions in maize. We assembled four complementary TF-target gene network layers, based on expression, protein-DNA interaction, trans-expression quantitative trait loci (eQTL), and cis-eQTL-supported interaction, from 46 Random Forest (RF)-inferred regulatory networks, 283 protein-DNA interaction assays, and eQTLs derived from 16 million SNPs across 304 inbred lines. Together these layers comprised ~4.6 million interactions. We then compared three strategies for integrating them, benchmarking each against published TF knockout data. A network-based approach, which represents every gene as a low-dimensional vector (embedding) learned from the combined network, outperformed the two overlap-based strategies, annotating over eight times more TFs (~3,000), agreeing most closely with gene knockout responses where predictions existed, and remaining robust when individual layers lacked data. The predictions recovered TF functions and predicted new regulators of hormone, developmental, and metabolic processes, which we prioritized per process and mapped to specific conditions. Using similarity on the low-dimensional vector representation (embedding), we further identified candidate functionally redundant or diverged TF paralogs. Because it relies only on data types now common across species, the framework provides a generalizable template for prioritizing regulatory genes in maize and other plants.

plant biology↗

bioRxiv2024

Stepwise neofunctionalization of the NF-κB family member c-Rel during vertebrate evolution

Adaptive immunity and the five vertebrate NF-{kappa}B/Rel family members first appeared in cartilaginous fish, suggesting that divergence and specialization within the NF-{kappa}B family helped facilitate the evolution of adaptive immunity. One specialized function of the NF-{kappa}B c-Rel protein in macrophages is the activation of Il12b, which encodes a key regulator of T-cell development. We found that c-Rel is a far more potent regulator of Il12b than of any other inducible genes in macrophages, with c-Rel regulation of Il12b dependent on its heightened intrinsic DNA-binding affinity. c-Rel homodimers regulate Il12b transcription in part via motifs with little resemblance to canonical NF-{kappa}B motifs. ChIP-seq experiments further defined distinct c-Rel DNA-binding preferences genome-wide, and X-ray crystallography of a c-Rel/RelA chimeric protein identified key amino acid changes that support the unique c-Rel properties. Unexpectedly, these changes, along with the c-Rel/RelA binding affinity differences, were largely restricted to mammalian species. Together, our findings reveal how a transcription factor family member can undergo a structural transition at a late stage of vertebrate evolution, resulting in an increased intrinsic DNA binding affinity and with clear functional consequences, presumably to support the increasing complexity of immune regulation.

immunology↗

bioRxiv2023

Multi-Omics Analysis Of Antiviral Interactions Of Elizabethkingia anophelis And Zika Virus

BackgroundThe microbial communities residing in the mosquito midgut play a key role in determining the outcome of mosquito pathogen infection. Elizabethkingia anophelis, originally isolated from the midgut of Anopheles gambiae, has drawn much attention due to its close association with Aedes and Anopheles mosquitoes, primary vectors of dengue virus and malaria parasites, respectively. E. anophelis possesses a broad-spectrum antiviral phenotype, yet a gap in knowledge regarding the mechanistic basis of its interaction with viruses exists. Methodology/Principal findingsTo further understand the antiviral interactions between E. anophelis and Zika virus (ZIKV), we utilized a non-targeted multi-omics approach, analyzing lipids, proteins, and metabolites of cell monolayers co-infected with ZIKV and E. anophelis. We further assessed the gene expression of ZIKV when cultured in the presence of E. anophelis. ZIKV cultured in the presence of E. anophelis resulted in an attenuated replicative fitness and unproductive virus infection. Further, in this treatment, we observed lower levels of the nonstructural protein 5 (NS5) and RNA-directed RNA polymerase (RdRp) protein. Lastly, a significant decrease in arginine levels, an essential requirement for viral replication and progression of viral infection was observed. Conclusions/SignificanceThis study provides insights into the molecular basis of E. anophelis antiviral phenotype. These findings improve our knowledge of how microbes and viruses interact to impact viral replication. In the future, our findings can be utilized to unravel the mechanism behind the antiviral phenotype of E. anophelis, and this can help develop novel paradigms for viral therapeutics. AUTHOR SUMMARYZika is a re-emerging disease and is endemic in many regions of sub-Saharan Africa, Asia and Latin America. It remains a major public health threat and lacks FDA-approved therapeutics or vaccines, hence the urgent need for the identification of alternative approaches that limit the transmission of the pathogens by its primary vector, Aedes spp. The microbial communities residing in the mosquito midgut play a key role in determining the outcome of mosquito pathogen infection. Flavobacteria dominates the mosquito midgut including Elizabethkingia, which is a gram-negative bacillus prevalent in Aedes and Anopheles species of mosquitoes. E. anophelis, a poorly studied midgut microbe, has a broad-spectrum antiviral phenotype, yet the mechanism of its antiviral action is unknown. In this study, we have identified several pathways as well as Zika virus proteins perturbed when the Zika virus is cultivated in the presence of E. anophelis. Our findings do not only provide insights into microbial, virus interaction but could be harnessed to develop novel antiviral tools.

microbiology↗

bioRxiv2023

Correlative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment

In the nucleus, biological processes are driven by proteins that diffuse through and bind to a meshwork of nucleic acid polymers. To better understand this interplay, we developed an imaging platform to simultaneously visualize single protein dynamics together with the local chromatin environment in live cells. Together with super-resolution imaging, new fluorescent probes, and biophysical modeling, we demonstrated that nucleosomes display differential diffusion and packing arrangements as chromatin density increases whereas the viscoelastic properties and accessibility of the interchromatin space remain constant. Perturbing nuclear functions impacted nucleosome diffusive properties in a manner that was dependent on local chromatin density and supportive of a model wherein transcription locally stabilizes nucleosomes while simultaneously allowing for the free exchange of nuclear proteins. Our results reveal that nuclear heterogeneity arises from both active and passive process and highlights the need to account for different organizational principals when modeling different chromatin environments.

biophysics↗

bioRxiv2023

Atypical Protein Kinase C Promotes its own Asymmetric Localisation by Phosphorylating Cdc42 in Polarising Cells

Atypical protein kinase C (aPKC) is a major regulator of cell polarity. Acting in conjunction with Par6, Par3 and the small GTPase Cdc42, aPKC becomes asymmetrically localised and drives the polarisation of cells. aPKC activity is crucial for its own asymmetric localisation, suggesting a hitherto unknown feedback mechanism contributing to polarisation. Here we show in the C. elegans zygote that the feedback relies on aPKC phosphorylation of Cdc42 at serine 71. The turnover of CDC-42 phosphorylation ensures optimal aPKC asymmetry and activity throughout polarisation by tuning Par6/aPKC association with Par3 and Cdc42. Moreover, turnover of Cdc42 phosphorylation regulates actomyosin cortex dynamics that are known to drive aPKC asymmetry. Given the widespread role of aPKC and Cdc42 in cell polarity, this form of self-regulation of aPKC may be vital for the robust control of polarisation in many cell types. Key findings/graphical abstract- Phosphorylation of CDC-42 by aPKC accelerates aPKC dissociation from CDC-42, limiting aPKC activity - CDC-42/aPKC dissociation promotes aPKC association with PAR-3 and, thereby, aPKC asymmetry due to actomyosin flow - Cycling of CDC-42 phosphorylation fuels the exchange of aPKC between anteriorly transported PAR-3 and aPKC-active CDC-42 complexes - Turnover of CDC-42 phosphorylation alternates its association with effectors, aPKC and MRCK-1, ensuring proper actomyosin dynamics O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/563985v2_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@e0ec65org.highwire.dtl.DTLVardef@c00b8dorg.highwire.dtl.DTLVardef@36565dorg.highwire.dtl.DTLVardef@160149a_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

ERα mediated gene state switching regulates the extent of the single-cell estrogen response

Gene regulation is complex, involving the coordination of hundreds of proteins that function to control genome accessibility, mediate enhancer-promoter interactions, and initiate transcription. At individual loci, transcriptional initiation is stochastic, resulting in short periods of nascent RNA synthesis known as transcriptional bursts. To understand how altered Estrogen Receptor function and cofactor recruitment regulates transcriptional bursting, we used single molecule imaging of estrogen responsive genes in Bisphenol A (BPA) treated cells. Using live cell imaging of the estrogen responsive TFF1 gene, we observe that cells treated with BPA exhibited burst initiation kinetics and burst sizes which were indistinguishable from cells induced with Estradiol (E2). However, we observed a 50% reduction in the number of active alleles in BPA treated cells. This effect is gene specific, as GREB1 was unperturbed. Although we observed no difference in chromatin accessibility, the TFF1 promoter exhibited an altered structure which coincided with reduced ER and cofactor binding. Lastly, deletion of the enhancer locus removed the BPA effect, indicating that enhancer function was perturbed. Our results demonstrate gene specific effects of altered ER recruitment and function which lead to a reduction of transcriptionally permissive states. Our work supports the model that the early estrogen response occurs from alleles in primed transcriptionally permissive states with additional inactive alleles contributing to the response over time.

cell biology↗

bioRxiv2023

Histopathology-assisted proteogenomics provides foundations for stratification of melanoma metastases

Here we describe the histopathology-driven proteogenomic landscape of 142 treatment-naive metastatic melanoma samples. We identified five proteomic subtypes that integrate the immune and stroma microenvironment components, and associate with clinical and histopathological parameters, providing foundations for an in-depth molecular classification of melanoma. Our study shows that BRAF V600 mutated melanomas display heterogeneous biology, where the presence of an oncogene-induced senescence-like phenotype improves patient survival. Therefore, we propose a mortality-risk-based stratification, which may contribute to a more personalized approach to patient treatment. We also found a strong association between tumor microenvironment composition, disease progression, and patient outcome supported by single-cell omic signatures that point to straightforward histopathological connective tissue-to-tumor ratio assessment for better informed medical decisions. A melanoma-associated signature of single amino acid variants (SAAV) responsible for remodeling the extracellular matrix was uncovered together with SAAV-derived neoantigen candidates as targets of anti-tumor immune responses. Overall, this study offers comprehensive stratifications of melanoma metastases that may help develop tailored strategies for diagnosing and treating the disease.

cancer biology↗

bioRxiv2023

Design of Cytotoxic T Cell Epitopes by Machine Learning of Human Degrons

Antigen processing is critical for producing epitope peptides that are presented by HLA molecules for T cell recognition. Therapeutic vaccines aim to harness these epitopes for priming cytotoxic T cell responses against cancer and pathogens, but insufficient processing often reduces vaccine efficacy through limiting the quantity of epitopes released. Here, we set out to improve antigen processing by harnessing protein degradation signals called degrons from the ubiquitin-proteasome system. We used machine learning to generate a computational model that ascribes a proteasomal degradation score between 0 and 100. Epitope peptides with varying degron activities were synthesized and translocated into cells using nontoxic anthrax proteins: protective antigen (PA) and the N-terminus of lethal factor (LFN). Immunogenicity studies revealed epitope sequences with a low score (<25) show pronounced T-cell activation but epitope sequences with a higher score (>75) provide limited activation. This work sheds light on the sequence-activity relationships between proteasomal degradation and epitope immunogenicity, through conserving the epitope region but varying the flanking sequence. We anticipate that future efforts to incorporate proteasomal degradation signals into vaccine designs will lead to enhanced cytotoxic T cell priming by vaccine therapeutics in clinical settings.

immunology↗