Biology subjects

Simon, S.

Publications and source records attributed to Simon, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Reactivation of neural signatures of food during REM-like sleep in the high-level visual cortex of monkeys

Can we tell what animals are dreaming about from their brain activity? This fascinating question has been explored extensively using the rodent hippocampus, where place cells are sequentially reactivated during sleep, consistent with replay of paths explored while awake. However, dreams involve vivid visual experiences, and whether analogous replays occur in the visual cortex has not been explored, that too in primates. To address this gap, we performed wireless neural recordings from the high-level visual (IT) and motor regions (PMv, PFC) in two monkeys while they viewed food images on a screen while awake, and afterwards while they slept in their natural setting. Decoders trained on sleep/wake neural activity in each region were able to accurately predict the ongoing sleep/wake state, as well as upcoming transitions between states. Interestingly, decoders trained to categorize neural responses to food (but not faces/objects) showed increased probability during REM-like sleep compared to NREM or awake states. Thus, behaviorally relevant visual stimuli seen while awake are reactivated during REM-like sleep. In other words, these monkeys saw food, faces and objects while awake, and dreamt selectively about food while sleeping.

neuroscience↗

bioRxiv2026

High-level visual and motor regions are doubly dissociated in controlled tasks but only at specific times during natural behaviors

Our knowledge of the neural basis of sensory and motor information processing comes largely from recording brain activity in controlled settings. This approach, while insightful, blinds us from understanding natural behaviors, which involve far richer visual inputs and far larger range of movements. The prevailing belief is that, during natural behaviors, movement information would modulate visual cortex, and visual inputs would modulate motor cortex. Alternatively, this mixing might only reflect correlations between sensory inputs and movements present during natural behavior. To resolve this issue, we performed wireless recordings from high-level visual (IT) and motor regions (PMv/PFC) in freely moving monkeys while they performed a natural task and a fixation task. In each task, we extracted visual and movement features and asked to what degree these features explained neural activity. In the fixation task, we found a striking double dissociation whereby visual (but not movement) features predicted neural activity in IT, whereas motor (but not visual) features predicted neural activity in PMv & PFC. This dissociation was far weaker in the natural task but present particularly at key events when the visual and motor features were less correlated. Thus, high-level sensory and motor regions in the brain are doubly dissociated under controlled conditions, and remain so at specific times during natural behavior.

neuroscience↗

bioRxiv2026

Single-cell and spatial transcriptomics resolve airway obliteration in bronchiolitis obliterans syndrome

Background: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation, and its most frequent phenotype is bronchiolitis obliterans syndrome (BOS), a fibrotic small-airway disease. Mechanistic work has focused on the immune compartment, yet intensified immunosuppression does not alter established disease. Aim: To resolve which structural cell states populate the BOS graft and how they are spatially organized during airway obliteration. Methods: We profiled explanted lungs from 33 BOS patients undergoing re-transplantation and 33 controls, combining single-nucleus RNA sequencing (14 BOS, 13 controls) with targeted spatial transcriptomics of 108 regions (27 BOS, 24 controls) and multiplex immunofluorescence validation. Single-nucleus data were integrated with a published restrictive allograft syndrome (RAS) atlas. Results: Across 175,128 nuclei and 1.67 million spatially resolved cells, BOS lungs harbored a profibrotic circuit of Aberrant Basaloid cells and CTHRC1+ fibrotic fibroblasts previously described in fibrotic lung diseases, including RAS. Spatial mapping identified a CXCL14+TNC+ injury-associated basal cell state arising early in the obliterative cascade, identifying basal cells as their major reservoir. CTHRC1+ fibroblasts expanded subepithelially replacing resident peribronchial fibroblasts, alongside a peribronchial vascular shift toward systemic venous endothelium. The circuit extended beyond the airway wall to the alveolar interface, defining two convergent remodeling fronts. Conclusion: BOS engages structural-cell circuits largely shared with RAS and fibrotic lung diseases, but along an airway-centered rather than parenchyma-centered axis. CLAD thus emerges as a spatial rather than cellular spectrum, defined by anatomical distribution more than cell identity. Shared structural programs may therefore be targetable across CLAD phenotypes.

cell biology↗

bioRxiv2026

Enhanced BCMA Antigen Density Increases Trogocytosis and Attenuates CAR T cell Function

BackgroundChimeric Antigen Receptor (CAR) T cell therapy targeting B-cell maturation antigen (BCMA) has demonstrated impressive clinical efficacy in relapsed/refractory multiple myeloma (MM). Nonetheless, disease relapse limits durable response for most patients. Trogocytosis of target antigen by effector cells has emerged as a potential contributor to reduced surface antigen density, CAR T cell dysfunction, and fratricide. Although {gamma}-secretase inhibitors (GSI) significantly increase cell surface BCMA density and decrease soluble BCMA (sBCMA), their effects on BCMA trogocytosis and the resulting impact on CAR T-cell function remain incompletely understood. MethodsWe investigated the effects of GSI on BCMA-directed CAR T cell function and trogocytosis using in vitro co-culture systems with MM cell lines across a spectrum of BCMA expression. We validated findings using confocal microscopy and cytotoxicity assays. Trogocytosis and fratricide were assessed in time-resolved functional studies. Phenotypic and functional differences between trogocytosis-positive (CAR T Trogo+) and trogocytosis-negative (CAR T) cells were evaluated using multiparametric flow cytometry, proteomic profiling, single-cell RNA sequencing (scRNA-seq), T-cell receptor (TCR) sequencing, and in vitro rechallenge assays. We also interrogated clinical samples from two Phase I trials (NCT03338972 and NCT03502577) which employed the identical CAR T cell construct with or without GSI respectively, to evaluate the relationship between trogocytosis, CAR T cell persistence, and treatment outcome. ResultsGSI driven increases in BCMA density on MM cell lines enhanced CAR T cell cytotoxicity but concomitantly increased trogocytosis, particularly in high-antigen-density cell lines-(H929+GSI vs H929; 30 min (P<0.0001), 1 h (P<0.0001), 2 h (P<0.0001), 6 h (P<0.0001), and 24 h (P<0.0001) and in CD4 CAR T cells (K562mCherry+GSI, CD4 vs CD8 CAR T cells;10 min (P=0.01), 2 h (P=0.01), and 6 h (P=0.004). Following BCMA acquisition, CAR T cells (CAR T Trogo) exhibited reduced proliferative capacity, diminished cytotoxic function (CAR T Trogo+ vs CAR T; (P=0.01), and an increase in markers of exhaustion/activation (CD4+ CAR T Trogo+ vs CD4 CAR T and CD8+ CAR T Trogo+ vs CAR T; PD-1+LAG-3+, PD-1+TIM-3+, and TOX+TIM-3 co-expression, (P=0.007, P<0.0001, P=0.006 and P=0.004, P=0.03, P=0.006). In fratricide assays, CAR T Trogo cells were susceptible to killing by naive CAR T cells. Single cell RNA-seq supports the phenotypic findings revealing transcriptional features of heightened activation and accelerated exhaustion in CAR T Trogo+ cells. Clinical phase I trial data confirm BCMA trogocytosis in patient samples. ConclusionsOur findings highlight the paradoxical effects of increased BCMA density on BCMA CAR T cell therapy: enhancement of initial tumor targeting and promotion of trogocytosis-associated dysfunction. Trogocytosis may contribute to antigen modulation, CAR T cell exhaustion, and fratricide, potentially muting the therapeutic benefits of enhanced antigen density. To optimize GSI and mitigate trogocytosis-associated resistance mechanism, future clinical trial designs should incorporate early time-point sampling, a sample size providing sufficient statistical power to determine an impact on CAR T cell persistence and treatment response, and mechanistic assessments.

cancer biology↗

bioRxiv2026

Coordinated expansion of CD163⁺ monocytes and immature CD177⁺ neutrophils marks severe neurotoxicity after CD19 CAR T cell therapy

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a major complication after CAR T cell therapy, but its underlying mechanisms remain poorly understood. We performed longitudinal immune profiling of paired whole blood and serum samples from patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) treated with CD19 CAR T cells. At peak neurotoxicity, high-dimensional mass cytometry and serum proteomics identified the expansion of CD163 monocytes and immature CD10lowCD101low neutrophils correlated with elevated serum ST2 and IL-2RA concentrations. Integrative immune module analysis identified these features among the strongest predictors of ICANS severity. Independent single-cell transcriptomic profiling validated the emergence of immunoregulatory CD163 monocytes and identified CD177 as a biomarker of ICANS-associated immature neutrophils. Together, these findings reveal a coordinated myeloid inflammatory network associated with ICANS and nominate candidate biomarkers and therapeutic targets for improving the safety of CAR T cell therapy. SignificanceWe demonstrate that immunoregulatory CD163+ monocytes and immature, activated CD177hiCD10lowCD101low neutrophils emerge in patients with moderate to severe ICANS at peak toxicity following CD19 CAR T cell therapy. These findings identify an uncharacterized myeloid network potentially contributing towards ICANS pathogenesis.

immunology↗

bioRxiv2026

Natural behavior elicits reliable neural signatures in high-level sensory and motor regions of freely moving monkeys

Natural behaviors are challenging to study because they involve large variations in sensory inputs and motor outputs across trials. Even the simple act of eating can involve seeing food from many angles and reaching for it differently each time. The prevailing view is that natural behaviors are more noisy compared to controlled tasks, and involve mixing of sensorimotor information. Alternatively, natural behaviors might elicit reliable neural signatures in high-level visual and motor regions which contain invariant representations, and involve correlated sensory and motor information that leads to apparent mixing. Here, we provide evidence for the latter possibility through wireless recordings in freely moving monkeys performing natural tasks as well as controlled screen tasks. During natural interactions with food, neural activity was decodable with striking fidelity, equivalent to that of food images. Key events during these interactions elicited distinct and reliable neural signatures that reflected the encoding priorities of each region. Visual and motor regions were clearly dissociated in screen tasks, but were dissociated only at specific events in the natural task. Neurons active while seeing food were reactivated during sleep. Taken together, our results reveal that reliable neural signatures in high-level sensory and motor regions form the neural substrates for natural behaviors.

neuroscience↗

bioRxiv2026

Dynamic tracking of social variables in simultaneous brain recordings of socially interacting monkeys

Primates are deeply social, but understanding the neural basis has been challenging since it has previously only been possible to record from single monkeys interacting with a social partner. Here, we performed simultaneous wireless neural recordings from two macaque monkeys interacting socially in a natural, unconstrained setting. Neural activity in each monkey encoded key social variables such as allogrooming state, partner identity and joint movements. Interestingly, neurons in the high-level visual cortex of each monkey continuously tracked a social favor signal, i.e. net duration of allogrooming given versus received, providing a neural basis for grooming reciprocity. In each monkey, neural activity was predicted better by his partners joints and neural activity, particularly while giving compared to receiving grooming. Thus, the receiver of grooming drove the social interaction, not the groomer. Taken together, our findings elucidate the rich and dynamic neural basis of primate social interactions in an ecologically valid setting.

neuroscience↗

bioRxiv2026

Dual blockade of LILRB1 and LILRB2 enhances antiviral immune responses in SIV infection

Restoring effective antiviral immunity remains a major challenge in HIV infection. Among emerging immune checkpoint molecules, the inhibitory receptors LILRB1 and LILRB2 have been proposed as therapeutic targets, yet their in vivo function remains undefined due to the lack of cross-reactive blocking antibodies for relevant preclinical models. To address this, we developed a dual-specific blocking monoclonal antibody, mac20G10, targeting cynomolgus macaque LILRB1 and LILRB2 and assessed its immunomodulatory activity in an SIV model of infection. Pharmacodynamics analyses demonstrated that mac20G10 persisted in circulation and engaged target myeloid cells for up to 14 days without detectable adverse effects. A single administration prior to SIVmac251 infection enhanced early myeloid immune activation, characterized by increased frequencies of CD80+ pDC and CD80+ monocyte/macrophage subsets in blood and lymphoid tissues. These changes were accompanied by increased plasma levels of IFN-{lambda}, IL8, and IL-1RA during acute infection. Although viral replication remained unchanged, mac20G10 treatment promoted the development of SIV-specific memory CD8 T-cell responses. Together, these findings provide in vivo evidence that LILRB1 and LILRB2 function as myeloid immune checkpoints restraining antiviral priming, supporting this pathway as a rational target for combination immunotherapeutic strategies aimed at achieving durable HIV remission during analytic treatment interruption.

immunology↗

bioRxiv2026

Smad7-based biologic targeting epidermis and stroma promotes healing of diabetic wounds in mice and pigs

This study aimed to identify novel mechanisms of diabetic wound healing defects and test a therapeutic intervention using diabetic mouse and pig models. We found Smad7 transgene expression in mouse epidermis promoted wound healing in diabetic mice. To isolate effects of Smad7 on wounds, we created a Smad7-based biologic (Tat-PYC-Smad7) that penetrated cells of the wound. Topical Tat-PYC-Smad7 treatment to diabetic pig and mouse wounds accelerated healing compared to vehicle controls. Tat-PYC-Smad7-treated wounds showed reduced TGF{beta}/NF{kappa}B signaling, faster re-epithelialization and better extracellular matrix remodeling. Tat-PYC-Smad7 also attenuated neutrophil NETosis, potentially acting through reductions in MPO enzymatic activity and MPO nuclear entry, consequently reducing chromatin decondensation and the release of NET components. Our study revealed that Tat-PYC-Smad7 promoted diabetic wound healing by targeting keratinocytes and neutrophils, providing insight into mechanisms of diabetic wound healing defects targetable by Smad7-based therapy.

immunology↗

bioRxiv2025

Vis-OCT Explorer: an open-source software for visible-light optical coherence tomography data processing

Background and objectivesVisible-light optical coherence tomography (vis-OCT) has enabled the visualization of retinal structures and functions beyond the capabilities of conventional OCTs. However, to reconstruct high-quality images, vis-OCT requires special post-processing, including balanced detection. An open-source, standardized vis-OCT data processing software is essential for clinical applications and translation of vis-OCT. MethodsWe developed Vis-OCT Explorer, an open-source, modular Python-based software for processing vis-OCT images. In addition to the standard spectral-domain OCT processing pipeline - including k-space resampling, dispersion compensation, and fast Fourier transformation - Vis-OCT Explorer offers unique dual-spectrometer balanced detection, short-time-Fourier transformation (STFT) based dispersion compensation coefficient optimization, and GPU-accelerated processing. We evaluated the reconstruction performance by quantifying a quality index extracted from individual B-scan images. We also assessed the repeatability of retinal thickness measurements by five operators on images acquired from different testing sites using the intraclass correlation coefficient (ICC) analysis. ResultsBalanced detection and STFT-based dispersion compensation significantly increased the quality index of reconstructed B-scan images. ICC values of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness measurements from four testing sites exceeded 0.8 in 87.5% of the macular-centered images. The ICC of RNFL thickness measurements on all optic nerve head-centered images is above 0.8, showing strong repeatability across users. ConclusionsVis-OCT Explorer provides high-quality image processing and enables highly repeatable measurements on vis-OCT human retinal images. It facilitates future multicenter clinical tests to validate vis-OCTs clinical efficacy.

bioengineering↗

bioRxiv2025

Targeted fusion of Antibody-Secreting Cells: unlocking monoclonal antibody production with hybridoma technology

Monoclonal antibodies (mAbs) produced by hybridoma technology have extensively proved their value for therapeutic, diagnostic, and biomedical research applications, despite the reported low fusion yields between short-lived B cells and immortal myeloma cells. To improve the efficiency of this process and accelerate the development of new mAbs, we characterized and isolated antibody-secreting cells (ASCs) from the spleen of immunized mice before cell fusion. This approach resulted in a high yield of hybridoma generation by increasing the probability of successive pairing between the most suitable cell fusion partners. Specifically, we developed an optimized workflow combining Fluorescence-Activated Cell Sorting (FACS) with antibody secretion assays, using a panel of five cell-surface markers (CD3, TACI, CD138, MHC-II, and B220) that allowed us to identify a particular ASC subset with key characteristics. Such ASCs exhibited a plasmablast phenotype with high MHC-II expression and secreted high levels of Ag-specific antibodies in immunized mice. These features were also found in hybridomas, suggesting a preferential fusion of myeloma cells with this ASCs subset. Finally, the targeted electrofusion of TACIhighCD138high sorted ASCs led to a 100% fusion yield compared to a non-targeted approach. In particular, over 60% of these generated hybridomas secreted Ag-specific mAbs. Collectively, these results pave the way for a highly efficient method to produce new mAbs by cell fusion, which could facilitate hybridoma generation and expand therapeutic applications of mAbs.

immunology↗

bioRxiv2025

Precise engineering of chimeric antigen receptor expression levels defines T cell identity and function

Chimeric Antigen Receptor (CAR) T therapy is a potent treatment for haematological malignancies, but T cell exhaustion reduces its efficacy in many patients. Although high CAR transgene levels appear to drive T cell exhaustion, the relationship between CAR expression levels, T cell function, and transcriptional identity is yet to be mapped at high resolution. Here, we harness a high-resolution microRNA-based control system to precisely modulate CAR transgene expression levels and assess the impact on T cell activation, gene expression and function. By post-transcriptionally modulating CAR abundance, we show that differential CAR levels significantly impact T cell proliferation, cytokine production and tonic signalling. T cells with high CAR expression become strongly activated even at low target antigen densities, while those with low CAR expression are triggered only by high concentrations of their target. Single-cell RNA sequencing of primary T cells expressing a broad range of CAR transcript levels revealed global transcriptional programmes that become dysfunctional with increased CAR abundance, expanding our understanding of T cell exhaustion. Notably, we identified a narrow CAR expression range where the exhaustion transcriptional state is not triggered, demonstrating that T cell exhaustion can be controlled by fine-tuning CAR levels. This work demonstrates that CAR expression levels are key determinants of T cell transcriptional identity and function and introduces a tractable method to precisely tune CAR expression and T cell activity.

synthetic biology↗

bioRxiv2024

Modifiers of genetic dominance at the Arabidopsis self-incompatibility locus retain proto-miRNA features and act through non-canonical gene silencing pathways

Self-incompatibility in flowering plants is a common mechanism that prevents self-fertilization and promotes outcrossing. In Brassicaceae, the self-incompatibility locus is highly diverse, with many alleles arranged in a complex dominance hierarchy and exhibiting monoallelic expression in heterozygote individuals. Monoallelic expression of the pollen self-incompatibility gene is achieved through the action of sRNA precursors that resemble miRNAs, although the underlying molecular mechanisms remain elusive. Here, we engineered Arabidopsis thaliana lines expressing components of the Arabidopsis halleri self-incompatibility system, and used a reverse genetics approach to pinpoint the pathways underlying the function of these sRNA precursors. We showed that they trigger a robust decrease in transcript abundance of the recessive self-incompatibility genes, but not through the canonical transcriptional or post-transcriptional gene silencing pathways. Furthermore, we observed that single sRNA precursors are typically processed into hundreds of sRNA molecules with a variety of sizes, abundance levels and ARGONAUTE loading preferences. Our results suggest that these seemingly arbitrary processing characteristics are essential for establishing the self-incompatibility dominance hierarchy, as they enable a single sRNA precursor from a dominant allele to effectively repress multiple recessive alleles, thus providing a unique example of how small RNAs mediate gene silencing within a highly complex regulatory network. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/591913v3_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@b32c02org.highwire.dtl.DTLVardef@10e65d3org.highwire.dtl.DTLVardef@3f14b3org.highwire.dtl.DTLVardef@1682d57_HPS_FORMAT_FIGEXP M_FIG C_FIG

plant biology↗

bioRxiv2023

Phylogenomics recovers multiple origins of portable case-making in caddisflies (Insecta: Trichoptera), the world's most common underwater architects

Caddisflies (Trichoptera) are among the most diverse groups of freshwater animals with more than 16,000 described species. They play an outsized role in freshwater ecology and environmental engineering in streams, rivers, and lakes. Because of this, they are frequently used as indicator organisms in biomonitoring programs. Despite their importance, key questions concerning the evolutionary history of caddisflies, such as the timing and origin of larval case-making, have been unanswered due to the lack of a well-resolved phylogenetic tree. To shed light on these questions in Trichoptera, we estimated a phylogenetic tree using a combination of transcriptomes and targeted enrichment data for 206 species, representing 48 of 52 extant families and 174 genera. We calibrated and dated the tree with a set of 33 carefully selected fossils. The first caddisflies originated in the Permian and the major suborders began to diversify in the Triassic. Ancestral state reconstruction and diversification analysis revealed that portable case-making evolved in three separate lineages and shifts in diversification occurred in concert with key evolutionary innovations other than case-making.

evolutionary biology↗

bioRxiv2023

S100A1's single cysteine is an indispensable redox-switch for the protection against diastolic calcium leakage in cardiomyocytes

The EF-hand calcium (Ca2+) sensor protein S100A1 combines inotropic with antiarrhythmic potency in cardiomyocytes (CM). Oxidative posttranslational modification (ox-PTM) of S100A1s conserved, single cysteine residue (C85) via reactive nitrogen species (i.e. S-nitrosylation or glutathionylation) was proposed to modulate conformational flexibility of intrinsically disordered sequence fragments and to increase the molecules affinity towards Ca2+. In light of the unknown biological functional consequence, we aimed to determine the impact of the C85 moiety of S100A1 as a potential redox-switch. We first uncovered that S100A1 is endogenously glutathionylated in the adult heart in vivo. To prevent glutathionylation of S100A1, we generated S100A1 variants that were unresponsive to ox-PTMs. Overexpression of wildtype (WT) and C85-deficient S100A1 protein variants in isolated CM demonstrated equal inotropic potency, as shown by equally augmented Ca2+ transient amplitudes under basal conditions and {beta}-adrenergic receptor ({beta}AR) stimulation. However, in contrast ox-PTM defective S100A1 variants failed to protect against arrhythmogenic diastolic sarcoplasmic reticulum (SR) Ca2+ leak and ryanodine receptor (RyR2) hypernitrosylation during {beta}-AR stimulation. Despite diastolic performance failure, C85-deficient S100A1 protein variants exerted similar Ca2+-dependent interaction with the RyR2 than WT-S100A1. Dissecting S100A1s molecular structure-function relationship, our data indicate for the first time that the conserved C85 residue potentially acts as a redox-switch that is indispensable for S100A1s antiarrhythmic but not its inotropic potency in CM. We therefore propose a model where C85s ox-PTM determines S100A1s ability to beneficially control diastolic but not systolic RyR2 activity.

molecular biology↗

bioRxiv2023

Microbial fingerprints reveal interaction between museum objects, curators and visitors

Microbiomes populate the border between humans and their environment. Whether the microbiome can be leveraged to gain information on human interaction with museum objects is unclear. To answer this question, museum objects varying in material and size from two museums, the Museum fur Naturkunde and the Pergamonmuseum in Berlin, Germany, which forms part of UNESCO World Heritage since 1999, were defined. In total 126 samples of natural and cultural heritage objects were taken with sterile nylon flocked swabs and subsequently subjected to 16S rRNA amplicon sequencing. By comparing the microbial composition of touched and untouched mollusc and fossil natural heritage objects we derived a robust microbial touch signature characterized by increased abundance of microbes known to be present in human skin. Application of this touch signature to cultural heritage objects from the Pergamonmuseum revealed areas of differential exposure to human contact on the Ishtar gate and Samal gate lions. Moreover, we were able to distinguish museum objects and personal office items touched by two different individuals with high sensitivity. Our results demonstrate that the microbial composition of museum objects gives insight into the degree of exposure to human contact, which is an important parameter for conservation and heritage science, and possibly provenance research.

microbiology↗

bioRxiv2022

Through the Random Forest: Ontogeny as a study system to connect prediction to explanation

As modeling tools and approaches become more advanced, ecological models are becoming more complex and must be investigated with novel methods of analysis. Machine learning approaches are a powerful toolset for exploring such complexity. While these approaches are powerful, results may suffer from well-known trade-offs between predictive and explanatory power. We employ an empirically rooted ontogenetically stage-structured consumer-resource model to investigate how machine learning can be used as a tool to root model analysis in mechanistic ecological principles. Applying random forest models to model output using simulation parameters as feature inputs, we extended established feature analysis into a simple graphical analysis. We used this graphical analysis to reduce model behavior to a linear function of three ecologically based mechanisms. From this model, we find that stability depends on the interaction between internal plant demographics that control the distribution of plant density across ontogenetic stages and the distribution of consumer pressure across ontogenetic stages. Predicted outcomes from these linear models rival accuracy achieved by our random forests, while explaining results as a function of ecological interactions.

ecology↗

bioRxiv2022

Community assessment of methods to deconvolve cellular composition from bulk gene expression

We evaluate deconvolution methods, which infer levels of immune infiltration from bulk expression of tumor samples, through a community-wide DREAM Challenge. We assess six published and 22 community-contributed methods using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells. Several published methods predict most cell types well, though they either were not trained to evaluate all functional CD8+ T cell states or do so with low accuracy. Several community-contributed methods address this gap, including a deep learning-based approach, whose strong performance establishes the applicability of this paradigm to deconvolution. Despite being developed largely using immune cells from healthy tissues, deconvolution methods predict levels of tumor-derived immune cells well. Our admixed and purified transcriptional profiles will be a valuable resource for developing deconvolution methods, including in response to common challenges we observe across methods, such as sensitive identification of functional CD4+ T cell states.

bioinformatics↗