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bioRxiv2026

HALPred-B: Host-Aware Linear B-Cell Epitope Prediction: Challenges, Limitations, and Variability Across Species

Predicting linear B-cell epitopes is a basic immunoinformatics task that has a direct impact on vaccine design and antibody engineering. Recent advances in machine learning have improved predictive performance, but most existing approaches are trained on aggregated datasets and assume that antigenic patterns are conserved across host organisms. This assumption ignores the immunological variability depending on the host and prevents generalizing the model across species. This is the first systematic host-wise evaluation where we present a systematic machine learning-based analysis of host-aware linear B-cell epitope prediction using curated datasets from the Immune Epitope Database (IEDB). We build separate datasets for human, mouse, and non-human primate hosts and assess several classification models, including Random Forest, Support Vector Machine (SVM), Gradient Boosting, XGBoost, and K-Nearest Neighbors (KNN). The models exploit feature representations derived from sequences, such as AAIndex descriptors, biochemical properties from ExPASy, and dipeptide composition. Our results show that predictive performance differs substantially across hosts. Models achieve up to 86.07% accuracy and 0.93 ROC-AUC on human datasets but lower performance on mouse and non-human primate datasets. This gap underlies dataset bias and sequence distribution differences, as well as the inability of existing features to capture host-specific immunological context. These results indicate that the prediction of linear B-cell epitopes is intrinsically host-specific, and a single global model does not generalize well across species. We propose to incorporate host-aware modeling strategies and organism-specific features for enhanced predictive reliability and biological relevance.

bioinformatics↗

bioRxiv2026

Single-cell multi-omics analysis reveals heterogeneity and plasticity of neutrophil states in response to immunotherapies

BackgroundTumor-associated neutrophils (TANs) are emerging as functionally heterogeneous and plastic cells in the tumor microenvironment. In immunologically cold tumors, elevated neutrophil abundance correlates with poor prognosis and resistance to immune checkpoint inhibition (ICI). Whether distinct anti-tumoral neutrophil states can be induced by different immunotherapies and how they relate to treatment efficacy remains unclear. MethodsUsing the syngeneic MOC2-huEGFR (M2h) mouse model of head and neck squamous cell cancer (HNSCC), we treated tumor-bearing mice with agonistic anti-CD40 monoclonal antibody (mAb) (aCD40), TNF, Cetuximab, or a combination of all three, designated Neutrophil Activating Therapy (NAT). In addition to evaluating anti-tumor efficacy, we performed single-cell multiomics RNA and protein sequencing, followed by bioinformatics analyses and flow cytometry validation. NAT-induced anti-tumor efficacy and related neutrophil states were also assessed in another cold tumor model, 9464D-GD2 neuroblastoma. Murine treatment-induced neutrophil gene signatures were then evaluated using clinical, proteomic, and transcriptomic data from HNSCC patients. ResultsFive transcriptionally distinct neutrophil states (N0-N4), including precursor state CD49d+ N4, were identified using the M2h model. N0 neutrophils (immunosuppressive/quiescent) dominated untreated tumors, but not in successful treatments. ISG+ N1 neutrophils and CCR3+ N3 neutrophils expanded by aCD40, TNF, and NAT treatment with anti-tumoral gene signatures and found more interacting with CD8+ T cells from bioinformatics analysis. N2 neutrophils reflected a recently established hypoxia-adapted state found in all treatments. ICAM1 (CD54) emerged as a marker of treatment-induced neutrophil activation, discriminating N1, N2, and N3 neutrophils from N0 neutrophils, validated by flow cytometry. In the 9464D-GD2 neuroblastoma model, NAT treatment also reduced the N0 dominance seen in untreated tumors in the HNSCC model but failed to induce anti-tumoral neutrophil states. In 23 HNSCC patients who received ICI therapy, ICAM1 protein expression in neutrophils trended toward association with responder status (TMA-level p=0.029), and ICAM1 neutrophil gene expression also trended toward association with improved overall survival in TCGA data (HR=0.75, p=0.059). ConclusionsDistinct immunotherapy-induced neutrophil states are defined by transcriptional profiles enriched in different functional pathways, associated with both anti-tumor and pro-tumor signatures. ICAM1 identifies activated neutrophils and potentially serves as a biomarker of ICI response in HNSCC, warranting further clinical validation. WHAT IS ALREADY KNOWN ON THIS TOPICNeutrophil heterogeneity has received increasing attention, with studies identifying antitumoral neutrophil populations, either at baseline or induced by treatment. Several effective treatment regimens involve an anti-CD40 agonist (aCD40) antibody, among them Neutrophil Activating Therapy (NAT), which combines aCD40, TNF, and a tumor antigen binding antibody designed to reprogram neutrophils. NAT could thus be particularly effective in cold, myeloid-rich tumors that are largely unresponsive to conventional immunotherapies such as checkpoint blockade, enacting these anti-tumoral effects through similar and different mechanisms; however, this has not been tested. WHAT THIS STUDY ADDSThis study adds a single-cell multi-omics framework for defining treatment-induced neutrophil heterogeneity in MOC2-huEGFR and 9464D-GD2 tumors, two immunologically cold models. It highlights ICAM1/CD54 and interferon-stimulated genes as markers of a dominant antitumor neutrophil state, while showing that neutrophil state composition variy across tumor models. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE, OR POLICYThese results support the efficacy of a myeloid-modulating therapy built around aCD40 and TNF in a cold murine head and neck cancer model, and to a lesser extent in a cold murine neuroblastoma model. ICAM1/CD54 expression in neutrophils was also identified as a promising marker of antitumor activity and treatment response. More broadly, this work suggests that incorporating aCD40 and/or TNF into existing treatment regimens could improve outcomes, while ICAM1/CD54-high neutrophils may serve as a useful therapeutic readout.

cancer biology↗

bioRxiv2026

DNCB shows hormetic effects in THP 1 cells: low-dose enhancement of metabolic activity

2,4-Dinitrochlorobenzene (DNCB) is a well-characterized skin sensitizer that has been widely used in immunological and toxicological research and, historically, in clinical immunotherapy. Although it is a well-investigated chemical, this is the first study focusing on the dose response behavior at low-level concentrations. The aim was to reveal potential hormetic effects due to its known Nrf2 inducting activity. Therefore, THP-1 cells were treated with low doses of DNCB and two endpoints were evaluated for hormetic responses: metabolic activity using a resazurin-based assay and immune activation by measuring CD86 and CD54 expression using flow cytometry. The results showed a significant hormetic effect on the metabolic endpoint at the lower cell density for both analyzed time points, and a hormetic tendency at the higher cell density. Metabolic activity increased to approximately 125% of the control at 0.05 micromolar DNCB. For the immunological endpoint a slight decrease in CD86 and CD54 surface marker expression was observed, up to -16% and up to -12% compared to control at 0.5 micromolar DNCB. These findings highlight the importance of including low dose concentrations when characterizing chemical dose-response relationships and evaluating toxicological risk.

pharmacology and toxicology↗

bioRxiv2026

Disease investigation in a New Zealand high-health pig herd reveals a divergent porcine adenovirus

Porcine adenoviruses are common in domestic pigs and are generally regarded as low-pathogenicity viruses associated with mild or subclinical infections. However, their diversity, host associations and disease potential remain poorly understood. Here, we investigated a disease outbreak in an immunologically naive 320-sow high-health hysterectomy-derived pig herd in New Zealand. The outbreak was characterised by anorexia, lethargy, diffuse cutaneous erythema, death in neonatal piglets, and an increased occurrence of mummified fetuses. Histopathological examination of a piglet revealed widespread intranuclear inclusion bodies within endothelial cells, indicative of systemic viral infection. Total RNA sequencing was performed on tissues from an affected piglet and mummified fetuses. Metatranscriptomic analysis identified an abundant adenovirus in multiple piglet and aborted fetus tissues, and de novo assembly recovered a 27,685-nucleotide genome. Phylogenetic analysis placed the virus within the genus Mastadenovirus but it formed a divergent lineage distinct from all previously characterised porcine adenoviruses. Despite sequence divergence, the genome retained the characteristic organisation of mastadenoviruses. Aside from a single detection of porcine kobuvirus identified at low abundance in the small intestine and colon from the piglet, no other viral pathogens were identified. The high viral abundance and systemic tissue distribution observed in both the piglet and fetus, together with the presence of widespread adenoviral inclusion bodies in the piglet, support an association between this novel adenovirus and the disease outbreak. These findings expand the diversity of porcine adenoviruses and suggest that previously unrecognised adenovirus lineages may contribute to reproductive and neonatal disease when introduced into immunologically naive high-health herds.

microbiology↗

bioRxiv2026

Transmission of mutated SARS-CoV-2 variants is favored by relatively prolonged infections due to delayed immunity

SARS-CoV-2 evolution enhanced viral fitness and immune evasion, extending the COVID-19 pandemic and resulting in millions of excess deaths. Viral diversity is generated within infected individuals, yet the timing and interplay of viral and immunological forces that drive transmissible evolution are incompletely understood. We developed a multi-scale within host phylodynamic (WiPhy) model of SARS-CoV-2 infection which couples viral replication, innate and acquired immune responses, and viral mutation. We then validated the model against quantitative viral and phylodynamic metrics. Model output predicts that typical acute infections rapidly generate genetic diversity due to accumulation of minor variants which in most cases do not achieve sufficient concentrations for transmission. Delayed innate immune responses correlate with higher peak viral load and diversification, allowing higher transmission risk of the founder virus or with a novel variant that is equally or less fit. In contrast, the risk of transmitting a fitter variant is highest during the ~10% of infections in which viral loads remain sufficiently high for transmission after 10-14 days. In these cases, non-sustained innate and/or weak acquired immune responses allow sufficient time for selection of a variant with one or more fitness enhancing non-synonymous mutations. Across a simulated cohort of ~1500 individuals, 5% of transmission risk came from variants with enhanced fitness from nonsynonymous mutations, and 13% of simulated infections accounted for 90% of fitter variant transmission risk. Our results highlight how the timing and interplay of viral and immunological forces within a host create bottlenecks that severely limit between host evolution.

evolutionary biology↗

bioRxiv2026

MHC Molecules on B Cell Microvilli Are Spatially Associated with IL-15Rα

Interleukin-15 (IL-15) trans-presentation (TP) by B cells is an important mechanism of T-cell activation; however, the spatial organisation of interleukin-15 receptor (IL-15R) relative to major histocompatibility complex (MHC) molecules on B-cell microvilli remains poorly understood. As microvilli protrude from the B-cell surface and may serve as sites of initial B cell-T-cell contact, the distribution of IL-15R and MHC molecules within these structures may be important during the earliest stages of T-cell recognition and activation. Here, we investigated the spatial association and molecular proximity of IL-15R with MHC class I and class II molecules on B-cell microvilli before immunological synapse formation, using confocal microscopy, stimulated emission depletion (STED) microscopy, stochastic optical reconstruction microscopy (STORM), and fluorescence lifetime imaging microscopy-based Forster resonance energy transfer (FLIM-FRET). Both MHC class I and class II molecules showed significant spatial association with IL-15R; however, the extent of colocalisation decreased as spatial resolution increased. STED microscopy revealed significant colocalisation between IL-15R and MHC class I, whereas STORM did not detect this association. In contrast, IL-15R and MHC class II remained significantly colocalised at both resolutions. FLIM-FRET further demonstrated molecular proximity between IL-15R and both MHC class I and class II molecules, with higher FRET efficiency observed for MHC class II. Collectively, these findings indicate that IL-15R is spatially organised in proximity to both MHC class I and class II molecules on B-cell microvilli before immunological synapse formation. This arrangement at potential sites of initial B-cell-T-cell contact may facilitate the coordination of IL-15 trans-presentation and antigen presentation during the earliest stages of B-cell-T-cell interactions.

cell biology↗

bioRxiv2026

Molecular Characterization of Gene-Product Relationships in the Wheat Gluten Complex for Reduced Immunogenicity Wheat Development

Immune-mediated reactions to wheat gliadins, including celiac disease and wheat allergies, affect ~1% of the U.S. population and are prevalent worldwide. Reducing the risk of inadvertent gluten exposure for individuals with celiac disease or wheat allergies requires the development of reduced immunogenicity wheat varieties which are suitable for human consumption. This study was designed with a view to improve our understanding of gene protein relationships at the complex wheat Gli1/Glu3 and Gli2 loci, and to develop genetic and molecular resources for breeding reduced-immunogenicity wheat lines. We conducted comprehensive genomic, biochemical, and immunological analyses of diverse wheat genetic resources, including aneuploid stocks, chromosome deficiency and interstitial deletion lines, Wasko omega null, the landrace San Pastore, Pegaso near isogenic lines lacking Gli1/Glu3/Gli2 loci, and progenies derived from a Wasko mega null X Pegaso(6A/6D) alpha null. Genomic characterization involved the targeted GlutEnSeq approach and PCR based DNA markers while biochemical and immunological analyses employed acid-urea PAGE, SDS PAGE, and ELISA. Integration of these complementary approaches resolved gliadin gene protein relationships at an unprecedented level. Notably, two F2; lines exhibited substantial reductions (both omega and alpha gliadins) due to the successful stacking of parental mutations. The resulting F2; progenies and associated DNA markers represent valuable resources for breeding wheat for reduced immunogenicity

genomics↗

bioRxiv2026

Oxidized TRX1 and DPP8/9 stabilize the MIA40-AIFM1 complex during intrinsic apoptosis

Mammalian cells execute diverse death programs with distinct immunological consequences. Mitochondrial outer membrane permeabilization (MOMP) drives typically immunologically silent intrinsic apoptosis by releasing cytochrome c and other proapoptotic proteins into the cytosol. Here, we show that MOMP also engages two established repressors of the pyroptosis-inducing NLRP1 inflammasome, oxidized thioredoxin-1 (oxTRX1) and catalytically active DPP8/9, in a coordinated redox and proteostasis program. Immediately after MOMP, oxTRX1 forms a disulfide with MIA40 Cys4 at the MIA40-AIFM1 interface. Subsequently, DPP8/9 cleave AK2, targeting this competing AIFM1 ligand for degradation. Biochemical reconstitution and cryo-EM reveal that oxTRX1 promotes AIFM1 dimerization and preferentially stabilizes MIA40-AIFM1 over AK2-AIFM1. Thus, redox-dependent complex assembly and selective proteolysis converge to favor MIA40-bound AIFM1 after MOMP. These findings suggest how post-MOMP remodeling could reinforce NLRP1 restraint during apoptosis and how disruption of this program could trigger pyroptosis.

cell biology↗

bioRxiv2014

Tracking global changes induced in the CD4 T cell receptor repertoire by immunization with a complex antigen using short stretches of CDR3 protein sequence.

The clonal theory of adaptive immunity proposes that immunological responses are encoded by increases in the frequency of lymphocytes carrying antigen-specific receptors. In this study, we measure the frequency of different TcRs in CD4+ T cell populations of mice immunized with a complex antigen, killed Mycobacterium tuberculosis, using high throughput parallel sequencing of the TcR beta chain. In order to track the changes induced by immunisation within this very heterogeneous repertoire, the sequence data were classified by counting the frequency of different clusters of short (3 or 4) continuous stretches of amino acids within the CDR3 repertoire of different mice. Both unsupervised (hierarchical clustering) and supervised (support vector machine) analysis of these different distributions of sequence clusters differentiated between immunised and unimmunised mice with 100% efficiency. The CD4+ T cell receptor repertoires of mice 5 and 14 days post immunisation were clearly different from that of unimmunised mice, but were not distinguishable from each other. However, the repertoires of mice 60 days post immunisation were distinct both from unimmunised mice, and the day 5/14 animals. Our results reinforce the remarkable diversity of the T cell receptor repertoire, resulting in many diverse private TcRs contributing to the T cell response even in genetically identical mice responding to the same antigen. Finally, specific motifs defined by short sequences of amino acids within the CDR3 region may have a major effect on TcR specificity. The results of this study provide new insights into the properties of the CD4+ adaptive T cell response.

Immunology↗

bioRxiv2014

Antimicrobial peptides play a functional role in bumblebee anti-trypanosome defense

Bumblebees, amongst the most important of pollinators, are under enormous population pressures. One of these is disease. The bumblebee and its gut trypanosome Crithidia bombi are one of the fundamental models of ecological immunology. Although there is previous evidence of increased immune gene expression upon Crithidia infection, recent work has focussed on the bumblebees gut microbiota. Here, by knocking down gene expression using RNAi, we show for the first time that antimicrobial peptides (AMPs) have a functional role in anti-Crithidia defense.

Immunology↗

bioRxiv2016

Antibody mediated epitope mimicry in the pathogenesis of Zika virus related disease

The association of Guillain-Barre syndrome with Zika virus infection raises suspicion of autoimmunity in the pathogenesis of Zika associated disease. Using computational analysis to identify predicted B and T cell epitopes, we assessed whether antibodies elicited by B cell epitopes in Zika virus may also target B cell epitopes in the human proteome. We detected amino acid motifs predicted to be B cell epitopes in Zika virus proteins which are also present in human proteins, including pro-neuropeptide Y (proNPY), NAV2 and other proteins with interacting neurophysiologic function. We examine the predicted MHC binding of peptides likely to provide T cell help to the potential mimic epitopes. Some potential mimic epitopes in Zika virus envelope have apparently strong T cell help, likely facilitating immunoglobulin class switch. We also identify epitope mimic commonalities with dengue serotypes 1 and 3. We hypothesize that antibodies to Zika virus epitopes may contribute to the pathogenesis of Zika-associated Guillain-Barre syndrome, microcephaly, and ocular lesions, and may be a driver of autoimmunity. The risk associated with responses to potential epitope mimics must be addressed in the development of vaccines and therapeutics for Zika virus infections.\n\nAuthor SummaryUsing computational immunologic analysis, we examine the possibility that anti-Zika antibodies are binding to mimic epitopes on human proteins and that this autoimmunity may be a driver for some of the clinical signs associated with Zika virus infection. These include Guillain Barre Syndrome, other neurophysiologic deficits, and the Zika Fetal Syndrome, including microcephaly. We identify specific proteins and epitopes to which anti-Zika antibodies may bind. The prospect that the pathogenesis of ZIKV may involve an antibody-mediated autoimmune component must be addressed in vaccine and therapeutic development.

Immunology↗

bioRxiv2016

Predicting Peptide-MHC Binding Affinities With Imputed Training Data

Predicting the binding affinity between MHC proteins and their peptide ligands is a key problem in computational immunology. State of the art performance is currently achieved by the allele-specific predictor NetMHC and the pan-allele predictor NetMHCpan, both of which are ensembles of shallow neural networks. We explore an intermediate between allele-specific and pan-allele prediction: training allele-specific predictors with synthetic samples generated by imputation of the peptide-MHC affinity matrix. We find that the imputation strategy is useful on alleles with very little training data. We have implemented our predictor as an open-source software package called MHCflurry and show that MHCflurry achieves competitive performance to NetMHC and NetMHCpan.

Immunology↗

bioRxiv2016

A generalized quantitative antibody homeostasis model: antigen saturation, natural antibodies and a quantitative antibody network

In a pair of articles we present a generalized quantitative model for the homeostatic function of clonal humoral immune system. In this second paper we describe how antibody production controls the saturation of antigens and the network of antibody interactions that emerges in the epitome space with the establishment of the immune system.\n\nEfficient control of antigens, be it self or foreign, requires the maintenance of antibody concentrations that saturate antigen to relevant levels. Simple calculations suggest that the observed diverse recognition of antigens by natural antibodies is only possible by cross-reactivity whereby particular clones of antibodies bind to diverse targets and shared recognition of particular antigens by multiple antibody clones contribute to the maintenance of antigen control. We also argue that natural antibodies are none else than the result of thymus independent responses against immunological self. We interpret and explain antibody production and function in a virtual molecular interaction space and as a network of interactions. Indeed the general quantitative (GQM) model we propose is in agreement with earlier models, confirms some assumptions and presumably provides the theoretical basis for the construction of a real antibody network using sequence and database data.

Immunology↗

bioRxiv2016

Depot Medroxyprogesterone Acetate is associated with increased Peripheral blood CD 3 and CD 4 T-Lymphocyte Counts among ART-Naive women living with HIV

IntroductionEstablishment of peripheral blood CD 3 and CD 4 lymphocyte counts is useful for immunological monitoring and staging of HIV. This forms the basis of management. This study evaluates total T lymphocyte and CD4 lymphocyte counts among women on DMPA and compares this to matched controls that were not on hormonal contraception.\n\nMaterials and MethodsThis case control study was conducted in the western Kenya city of Kisumu. Participants were WHO stage I and II ART naive HIV-positive women. The cases were enrolled in the institutional family planning clinic and must have had an intramuscular injection of DMPA within a three month period. We used a standard provider initiated questionnaire to collect social and demographic information. Peripheral blood CD 3 and CD 4 lymphocyte counts were determined using BD-Facs-count . Data was entered and analysed using SPSS(R) Version 17.\n\nResultsA total of 138 participants were recruited into the study, 66 controls and 54 cases. The median ages were 26 and 28 respectively. The median CD 3 lymphocyte counts among controls and cases were 1628 and (p=0.004) while median CD4 lymphocyte counts are 649 (p=0.02).\n\nConclusionUse of the progestin DMPA is associated with an increase in median in CD3 and CD 4 I lymphocyte counts. Although the clinical benefits of this increase is unclear, DMPA is safe for use among women living with HIV.

Immunology↗

bioRxiv2017

Do maternal antibodies facilitate hemagglutinin imprinting to influenza A viruses encountered early in childhood?

In a recent study, we showed evidence for childhood HA imprinting, a phenomenon in which children develop preferential, lifelong immune memory against zoonotic influenza viruses with hemagglutinin (HA) antigens in the same phylogenetic group as the first influenza virus encountered in childhood (Gostic et al. 2016). Although our original study showed strong, population-level HA imprinting effects, it did not resolve the underlying immunological mechanisms.\n\nSimilar immune imprinting phenomena, where individuals preferentially recall immune responses primed early in life, also influence seasonal influenza epidemiology via antigenic seniority (Lessler et al. 2012) and original antigenic sin (Francis 1960), yet the mechanisms underlying all these childhood immune imprinting phenomena remain poorly understood (Cobey & Hensley 2017). A recent letter from Dr. H. Lemke (Lemke 2017) suggested that these childhood imprinting effects might be mediated by the combined action of maternal antibodies (mAbs) and influenza antigen. In other words, that imprinting may require that children are exposed to influenza A virus in the first year of life, while maternal antibodies are still present.

immunology↗

bioRxiv2017

Quantification of inter-sample differences in T cell receptor sequences

Inter-sample comparisons of the T cell receptor (TCR) repertoire are crucial for gaining a better understanding into the immunological states determined by different collections of T cells from different donor sites, cell types, and genetic and pathological backgrounds. As a theoretical approach for the quantitative comparison, previous studies utilized the Poisson abundance models and the conventional methods in ecology, which focus on the abundance distribution of observed TCR sequences. However, these methods ignore the details of the measured sequences and are consequently unable to identify sub-repertoires that might have the contributions to the observed inter-sample differences. In this paper, we propose a new comparative approach based on TCR sequence information, which can estimate the low-dimensional structure by projecting the pairwise sequence dissimilarities in high-dimensional sequence space. The inter-sample differences are then quantified according to information-theoretic measures among the distributions of data estimated in the embedded space. Using an actual dataset of TCR sequences in transgenic mice that have strong restrictions on somatic recombination, we demonstrate that our proposed method can accurately identify the inter-sample hierarchical structure, which is consistent with that estimated by previous methods based on abundance or count information. Moreover, we identified the key sequences that contribute to the pairwise sample differences. Such identification of the sequences contributing to variation in immune cell repertoires may provide substantial insight for the development of new immunotherapies and vaccines.

immunology↗

bioRxiv2017

Phenolic glycolipid facilitates mycobacterial escape from a microbicidal population of tissue-resident macrophages

Mycobacterium tuberculosis enters the host in aerosol droplets deposited in lung alveoli where the bacteria first encounter lung-resident alveolar macrophages. We studied the earliest mycobacterium-macrophage interactions in the optically transparent zebrafish. We find that the first-responding resident macrophages can phagocytose and eradicate infecting mycobacteria. So, to establish a successful infection, mycobacteria must escape out of the initial resident macrophage into growth-permissive monocytes. We define a critical role for the membrane phenolic glycolipid (PGL) in engineering this transition to a permissive niche. PGL activates the STING cytosolic sensing pathway, thereby inducing the chemokine CCL2 that recruits permissive peripheral monocytes. The bacteria then transfer from resident macrophage to recruited monocyte via transient fusion of the two immune cells. We show that interrupting this bacterial strategy so as to prolong the mycobacterial sojourn in resident macrophages promotes clearing of infection. Because PGL-dependent CCL2 induction is conserved in human alveolar macrophages, our findings suggest the potential of immunological or pharmacological PGL-blocking interventions to prevent tuberculosis.

immunology↗

bioRxiv2017

Modeling of cytometry data in logarithmic space: when is a bimodal distribution not bimodal?

Recent efforts in systems immunology lead researchers to build quantitative models of cell activation and differentiation. One goal is to account for the distributions of proteins from single-cell measurements by flow cytometry or mass cytometry as a readout of biological regulation. In that context, large cell-to-cell variability is often observed in biological quantities. We show here that these readouts, viewed in logarithmic scale may result in two easily-distinguishable modes, while the underlying distribution (in linear scale) is unimodal. We introduce a simple mathematical test to highlight this mismatch. We then dissect the flow of influence of cell-to-cell variability proposing a graphical model which motivates higher-dimensional analysis of the data. Finally we show how acquiring additional biological information can be used to reduce uncertainty introduced by cell-to-cell variability, helping to clarify whether the data is uni- or bimodal. This communication has cautionary implications for manual and automatic gating strategies, as well as clustering and modeling of single-cell measurements.

immunology↗