Biology subjects

Gore, J.

Publications and source records attributed to Gore, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Growth rate and yield are not constrained by a trade-off in microbes

Ecological theory traditionally posits widespread trade-offs in organismal growth, survival, and reproduction. One core trade-off is the relation between maximum intrinsic growth rate (r) and carrying capacity (K), proposed as a key mechanism explaining species coexistence and the maintenance of biodiversity. To quantify how r relates to K in microbes, we analyzed more than 70,000 microbial growth curves in dozens of media conditions. In this set, we observed a strong positive correlation between r and K, challenging classic life-history expectations of a trade-off. This unexpected "trade-up" can be recovered by a model assuming a non-zero maintenance cost in cells. The model predicts a stronger trade-up under stress conditions that reduce growth rate, consistent with empirical data showing that salinity stress strengthens the trade-up. We also found that community assembly weakens but does not eliminate this positive r-K relationship. The robust growth-yield trade-up between species contrasts with patterns within species. Single-gene knockout datasets in Escherichia coli and budding yeast show no or only weak r-K relationships. Together, our results suggest that the lack of strong trade-offs between growth rate and carrying capacity may be widespread across species, emphasizing the importance of alternative trade-offs and coexistence mechanisms beyond the classical r-K framework.

ecology↗

bioRxiv2026

Nutrient availability shapes the diversity and structure ofmicrobial communities

Nutrients are key drivers of microbial community structure, yet we lack a data-driven quantitative framework linking nutrient environments to community assembly. Here, using controlled microcosm experiments, we systematically probe the effects of nutrient number, concentration, and type on community diversity and structure. To explain these effects, we construct a minimal consumer-resource model incorporating resource competition and cross-feeding. We find that cross-feeding network structure is critical: only shallow, wide networks -- where several byproducts are produced from a few supplied nutrients in a few trophic layers -- reproduce a linear increase in diversity with the number of supplied nutrients. We also perform new experiments varying nutrient concentration and reveal that diversity slowly decreases with increasing concentration. We explain this finding by incorporating consumption-dependent toxicity into the model, consistent with spent-media measurements. This extended model not only recapitulates virtually all observed patterns but makes an independent prediction: at high nutrient concentrations, communities should be enriched in bistable species pairs, which we confirm experimentally. Our work demonstrates that minimal data-driven consumer-resource frameworks -- systematically constrained by experiments -- can unify and predict a broad range of nutrient-community relationships.

ecology↗

bioRxiv2026

Interspecies interactions drive community-level selection in microbial coalescence

It has long been debated in ecology whether communities behave as cohesive units or as loose collections of independent species. Here, we study this question in the context of community coalescence, the mixing of previously isolated communities, using bacterial microcosm experiments combined with ecological modeling. Our results demonstrate that interspecies interaction strength determines whether communities or species are the units of selection during coalescence. When interactions are moderate to strong, one parental community consistently outcompetes the other, indicating community-level selection. In contrast, under weak interactions, species fates are uncorrelated and the two communities contribute equally to the coalesced outcome, indicating the absence of community-level selection. These patterns extend to communities derived from natural samples with greater taxonomic diversity and richness. Furthermore, we identify two distinct regimes underlying community-level selection in experiments with different media conditions: an emergent regime in which collective dynamics shape outcomes that cannot be predicted from species traits alone, and a top-down regime where dominant species determine the winning community. Together, these results reconcile conflicting observations on community-level selection during community coalescence by demonstrating that communities behave as cohesive units only when interactions are sufficiently strong.

ecology↗

bioRxiv2025

Microbial communities demonstrate robustness in stressful environments due to predictable composition shifts

Environmental stress reduces species growth rates, but its impact on the function of microbial communities is less clear. Here, we experimentally demonstrate that increasing salinity stress shifts community composition towards species with higher growth rates. As a result, the mean community growth rate is more robust to increasing stress than the growth of individual species. We show this by propagating natural aquatic communities at multiple salinities and mapping the observed diversity onto the measured salinity performance curves of >80 bacterial isolates. We further validate these results with pairwise species competitions and in metagenomic data of natural communities sampled from estuarine environments. A Lotka-Volterra model including mortality and salinity-dependent growth rates recapitulates the observed robustness of community growth sustained by more abundant faster growers at high salinity. These results extend to other environmental stressors and point to fundamental mechanisms with which communities maintain growth despite deteriorating conditions.

microbiology↗

bioRxiv2025

Topological Analysis of the Human Lymph Node Reticular Network Predicts Outcome in Breast Cancer

Axillary lymph nodes (ALN) initiate local immune responses in breast cancer (BC) but how and when ALN become dysfunctional, facilitating metastasis, is unclear. We use unbiased computational approaches to quantify features of ALN stromal architecture. We identify PDGFR{beta} as a robust, immunomarker for human fibroblastic reticular cells (FRC) and use it to quantify how FRC network topology changes during BC progression and after treatment. ALN (n = 331) from 179 BC patients and 23 benign reactive controls were assessed for FRC network metrics, including lacunarity and branchpoints, alongside de-identified clinico-pathological data. We find in node-negative, triple-negative BC, neoadjuvant treatment induced denser FRC networks which correlated with improved survival. Conversely, denser FRC networks in node-positive patients correlated with worsened survival, regardless of BC subtype or treatment. Further, increased FRC alignment within metastases improved survival. We show that FRC network topology predicts prognosis in BC, providing a new avenue for mechanistic, translational research.

pathology↗

bioRxiv2025

Structured interactions explain the absence of keystone species in synthetic microcosms

In complex ecosystems, the loss of certain species can trigger a cascade of secondary extinctions and invasions. However, our understanding of the prevalence of these critical "keystone" species and the factors influencing their emergence remains limited. To address these questions, we experimentally assembled microcosms from 16 marine bacterial species and found that multiple extinctions and invasions were exceedingly rare upon removal of a species from the initial inoculation. This was true across eight different environments with either simple carbon sources (e.g., glucose) and more complex ones (e.g. glycogen). By employing a generalized Lotka-Volterra model, we could reproduce these results when interspecies interactions followed a hierarchical pattern, wherein species impacted strongly by one species were also more likely to experience strong impacts from others. Such a pattern naturally emerges due to observed variation in carrying capacities and growth rates. Furthermore, using both statistical inference and spent media experiments, we inferred interspecies interaction strengths and found them consistent with structured interactions. Our results suggest that the natural emergence of structured interactions may provide community resilience to extinctions.

systems biology↗

bioRxiv2024

Cell-type specific autophagy in human leukocytes

Autophagy is a naturally conserved mechanism crucial for degrading and recycling damaged organelles and proteins to support cell survival. This process slows biological ageing and age-related disease in preclinical models. However, there has been little translation of autophagy to the clinic, and we have identified a lack of measurement tools for physiological human autophagy as a barrier. To address this, we have previously developed a direct measurement tool for autophagy in pooled human peripheral blood mononuclear cells (PBMCs) in the context of whole blood. In order to better understand how autophagy behaves and changes in humans, we measured human autophagic flux using flow cytometry in 19 cell sub-populations in whole blood to retain physiological flux. Autophagic flux was different between different cell types, being highest in B lymphocytes and lowest in T lymphocytes and monocytes. Autophagic flux also varied with sex, being higher in monocytes in females compared with males. In keeping with previous observations in humans, autophagy also increased with ageing at sub-population levels. Importantly, we found that only monocytes - specifically, non-classical monocytes - displayed increased autophagic flux following amino acid withdrawal, underscoring the importance of population selection for measurement of autophagic flux during nutrient restriction studies in humans. Collectively, these data show PBMC population level analysis improves sensitivity of human autophagic flux measurement.

cell biology↗

bioRxiv2024

Ecosystem stability relies on diversity difference between trophic levels

The stability of ecological communities has a profound impact on humans, ranging from individual health influenced by the microbiome to ecosystem services provided by fisheries. A long-standing goal of ecology is the elucidation of the interplay between biodiversity and ecosystem stability, with some ecologists warning of instability due to loss of species diversity while others arguing that greater diversity will instead lead to instability. Here, by considering a minimal two-level ecosystem with multiple predator and prey species, we show that stability does not depend on absolute diversity but rather on diversity differences between levels. We discovered that increasing diversity in either level first destabilizes but then stabilizes the community (i.e., a re-entrant stability transition). We therefore find that it is the diversity difference between levels that is the key to stability, with the least stable communities having similar diversities in different levels. An analytical stability criterion is derived, demonstrating quantitatively that the critical diversity difference is determined by the correlation between how one level affects another and how it is affected in turn. Our stability criterion also applies to consumer-resource models with other forms of interaction such as cross-feeding. Finally, we show that stability depends on diversity differences in ecosystems with three trophic levels. Our finding of a non-monotonic dependence of stability on diversity provides a natural explanation for the variety of diversity-stability relationships reported in the literature, and emphasizes the significance of level structure in predicting complex community behaviors.

ecology↗

bioRxiv2024

Collective dynamical regimes predict invasion success and impacts in microbial communities

Invasions of microbial communities by species such as pathogens can have significant impacts on ecosystem services and human health1-9. Predicting the outcomes of these invasions, however, remains a challenge. Various theories propose that these outcomes depend on either characteristics of the invading species10-12 or attributes of the resident community13-16, including its composition and biodiversity3,17-19. Here we used a combination of experiments and theory to show that the interplay between dynamics, interaction strength, and diversity determine the invasion outcome in microbial communities. We found that the communities with fluctuations in species abundance are both more invasible and more diverse than stable communities, leading to a positive diversity-invasibility relationship among communities assembled in the same environment. As predicted by theory, increasing interspecies interaction strength and species pool size leads to a decrease of invasion probability in our experiment. Although diversity-invasibility relationships are qualitatively different depending upon how the diversity is changed, we provide a unified perspective on the diversity-invasibility debate by showing a universal positive correspondence between invasibility and survival fraction of resident species across all conditions. Communities composed of strongly interacting species can exhibit an emergent priority effect in which invader species are less likely to colonize than species in the original pool. However, in this regime of strong interspecies interactions, if an invasion is successful, it causes larger ecological effects on the resident community than when interactions are weak. Our results demonstrate that the invasibility and invasion effect are emergent properties of interacting species, which can be predicted by simple community-level features.

ecology↗

bioRxiv2024

Repulsion from slow-diffusing nutrients improves chemotaxis towards moving sources

Chemotaxis, or the following of chemical concentration gradients, is essential for microbes to locate nutrients. However, microbes often display paradoxical behaviors, such as Escherichia coli being repelled by several amino acids. Here, we explore chemotaxis towards a moving source and demonstrate that when multiple nutrients are released from the source repulsion from certain nutrients actually improves chemotaxis towards the source. Because a moving source leaves most of the nutrient plume behind it, simply following the concentration gradient results in aiming behind the source and failing to intercept it. However, when attraction to a fast-diffusing nutrient and repulsion from a slow-diffusing nutrient are combined, motion in a new direction emerges and the chance of intercepting the source is increased up to six-fold. We demonstrate that this "differential strategy" is robust against numerous variations, including order-of-magnitude increases in the repellent release rate. Finally, we leverage existing data to show that E. coli is attracted to fast-diffusing amino acids and repelled by slow-diffusing ones, suggesting it may utilize a differential strategy and providing an explanation for its repulsion from these amino acids. Our results thus illuminate new possibilities in how microbes can integrate signals from multiple gradients to accomplish the difficult chemotactic tasks.

ecology↗

bioRxiv2023

Multistability driven by cooperative growth in microbial communities

Microbial communities often exhibit more than one possible stable composition for the same set of external conditions1-7. In the human microbiome, persistent changes in species composition and abundance are associated with health and disease states8. The main drivers of these alternative stable states remain relatively unknown9. Here we experimentally demonstrate that a cross-kingdom community, composed of six species relevant to the respiratory tract, displays four alternative stable states each dominated by a different species. In pairwise coculture, we observe widespread bistability among species pairs, providing a natural origin for the multistability of the full community. In contrast with the common association between bistability and antagonism, experiments reveal many positive interactions within and between community members. We find that multiple species display self-facilitation, or cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A tailored biochemical screening assay reveals that glutamate supplementation either reduces or eliminates cooperativity in the growth of several species, and we confirm that such supplementation reduces the extent of bistability across pairs and reduces multistability in the full community. Our findings provide a mechanistic explanation of how cooperative growth rather than competitive interactions can underlie multistability in microbial communities.

microbiology↗

bioRxiv2023

Complex ecosystems lose stability when resource consumption is out of niche

Natural communities exhibit diverse dynamics, encompassing global stability, multi-stability, periodic oscillations, and chaotic fluctuations in species abundances. Resource-consumer interactions provide a lens for mechanistic understanding of community behaviors, yet only a globally stable equilibrium can exist in the original MacArthur resource-consumer model. Here we find that diverse dynamics emerges when species consume resources that contribute little to their own growth. Key to understanding these results is comparison of niche range (difference between growth-promoting resources of similar species) and consumption range (difference between growth-promoting resources and the resources that are actually consumed). If the consumption range is small, we observe global stability as in the MacArthur model. But when consumption range increases to about the niche range, stability is lost, giving rise to emergent alternative stable states, globally stable states but with species extinction, and slightly later, persistent fluctuations. Given its importance in dictating stability, we define the ratio between consumption and niche ranges as encroachment, and find that it predicts key community properties like diversity and attractor basins even after the instability transition. In particular, after the loss of stability (encroachment greater than one), species extinction increases approximately linearly with encroachment. Since encroachment relies only on intrinsic species properties, community stability is resilient to environmental changes such as resource supply and mortality rate. Encroachment provides a framework for capturing resource competition due to growth-consumption inconsistency in complex communities as well as a robust quantitative characterization of the resulting emergent dynamics.

ecology↗

bioRxiv2023

Interfacial morphodynamics of proliferating microbial communities

In microbial communities, various cell types often coexist by occupying distinct spatial domains. What determines the shape of the interface between such domains--which in turn influences the interactions between cells and overall community function? Here, we address this question by developing a continuum model of a 2D spatially-structured microbial community with two distinct cell types. We find that, depending on the balance of the different cell proliferation rates and substrate friction coefficients, the interface between domains is either stable and smooth, or unstable and develops finger-like protrusions. We establish quantitative principles describing when these different interfacial behaviors arise, and find good agreement both with the results of previous experimental reports as well as new experiments performed here. Our work thus helps to provide a biophysical basis for understanding the interfacial morphodynamics of proliferating microbial communities, as well as a broader range of proliferating active systems.

biophysics↗

bioRxiv2023

Identification of functional white matter networks in BOLD fMRI

White matter signals in resting state blood oxygen level dependent functional magnetic resonance (BOLD-fMRI) have been largely discounted, yet there is growing evidence that these signals are indicative of brain activity. Understanding how these white matter signals capture function can provide insight into brain physiology. Moreover, functional signals could potentially be used as early markers for neurological changes, such as in Alzheimers Disease. To investigate white matter brain networks, we leveraged the OASIS-3 dataset to extract white matter signals from resting state BOLD-FMRI data on 711 subjects. The imaging was longitudinal with a total of 2,026 images. Hierarchical clustering was performed to investigate clusters of voxel-level correlations on the timeseries data. The stability of clusters was measured with the average Dice coefficients on two different cross fold validations. The first validated the stability between scans, and the second validated the stability between subject populations. Functional clusters at hierarchical levels 4, 9, 13, 18, and 24 had local maximum stability, suggesting better clustered white matter. In comparison with JHU-DTI-SS Type-I Atlas defined regions, clusters at lower hierarchical levels identified well defined anatomical lobes. At higher hierarchical levels, functional clusters mapped motor and memory functional regions, identifying 50.00%, 20.00%, 27.27%, and 35.14% of the frontal, occipital, parietal, and temporal lobe regions respectively.

neuroscience↗

bioRxiv2023

Resource competition can explain simplicity in microbial community assembly

Predicting the composition and diversity of communities is a central goal in ecology. While community assembly is considered hard to predict, laboratory microcosms often follow a simple assembly rule based on the outcome of pairwise competitions. This assembly rule predicts that a species that is excluded by another species in pairwise competition cannot survive in a multispecies community with that species. Despite the empirical success of this bottom-up prediction, its mechanistic origin has remained elusive. In this study, we elucidate how this simple pattern in community assembly can emerge from resource competition. Our geometric analysis of a consumer-resource model shows that trio community assembly is always predictable from pairwise outcomes when one species grows faster than another species on every resource. We also identify all possible trio assembly outcomes under three resources and find that only two outcomes violate the assembly rule. Simulations demonstrate that pairwise competitions accurately predict trio assembly with up to 100 resources and the assembly of larger communities containing up to twelve species. We then further demonstrate accurate quantitative prediction of community composition using harmonic mean of pairwise fractions. Finally, we show that cross-feeding between species does not decrease assembly rule prediction accuracy. Our findings highlight that simple community assembly can emerge even in ecosystems with complex underlying dynamics. SignificanceMultispecies microbial communities play an essential role in the health of ecosystems ranging from the ocean to the human gut. A major challenge in microbial ecology is to understand and predict which species can coexist within a community. While a simple empirical rule utilizing only pairwise outcomes successfully predicts multispecies laboratory communities, its mechanistic origin has remained unexplained. Here, we find that the observed simplicity can emerge from competition for resources. Using a generic consumer-resource model, we demonstrate that community assembly of highly complex ecosystems is nevertheless well predicted by pairwise competitions. Our results argue that community assembly can be surprisingly simple despite the potential complexity associated with competition and crossfeeding of many different resources by many different species.

ecology↗

bioRxiv2023

SpliceMutr enables pan-cancer analysis of splicing-derived neoantigen burden in tumors

Aberrant alternative splicing can generate neoantigens, which can themselves stimulate immune responses and surveillance. Previous methods for quantifying splicing-derived neoantigens are limited by independent references and potential batch effects. Here, we introduce SpliceMutr, a bioinformatics approach and pipeline for identifying splicing derived neoantigens from paired tumor normal data. SpliceMutr facilitates the identification of tumor-specific antigenic splice variants, predicts MHC-binding affinity, and estimates splicing antigenicity scores per gene. By applying this tool to genomic data from The Cancer Genome Atlas (TCGA), we generate splicing-derived neoantigens and neoantigenicity scores per sample and across all cancer types and find numerous correlations between splicing antigenicity and well-established biomarkers of anti-tumor immunity. Notably, carriers of mutations within splicing machinery genes have higher splicing antigenicity, which provides support for our approach. Further analysis of splicing antigenicity in cohorts of melanoma patients treated with mono- or combined immune checkpoint inhibition suggest that the abundance of splicing antigens is reduced post-treatment from baseline in patients who progress, likely because of an immunoediting process. We also observe increased splicing antigenicity in responders to immunotherapy, which may relate to an increased capacity to mount an immune response to splicing-derived antigens. This new computational tool provides novel analytical capabilities for splicing antigenicity and is openly available for further immuno-oncologic analysis.

cancer biology↗

bioRxiv2023

Biodiversity is enhanced by sequential resource utilization and environmental fluctuations via emergent temporal niches

How natural communities maintain their remarkable biodiversity and which species survive in complex communities are central questions in ecology. Resource competition models successfully explain many phenomena but typically predict only as many species as resources can coexist. Here, we demonstrate that sequential resource utilization, or diauxie, with periodic growth cycles can support many more species than resources. We explore how communities modify their own environments by sequentially depleting resources to form sequences of temporal niches, or intermediately depleted environments. Biodiversity is enhanced when community-driven or environmental fluctuations modulate the resource depletion order and produce different temporal niches on each growth cycle. Community-driven fluctuations under constant environmental conditions are rare, but exploring them illuminates the temporal niche structure that emerges from sequential resource utilization. With environmental fluctuations, we find most communities have more stably coexisting species than resources with survivors accurately predicted by the same temporal niche structure and each following a distinct optimal strategy. Our results thus present a new niche-based approach to understanding highly diverse fluctuating communities.

systems biology↗

bioRxiv2022

Strong Ethanol- and Frequency-Dependent Ecological Interactions in a Community of Wine-Fermenting Yeasts

Natural wine fermentation is carried out by the complex consortia of microorganisms native to grapes and winery equipment, rather than by inoculation with industrial yeast strains. While this diversity of yeasts can result in an increased repertoire of wine flavors and aromas, it can also result in the inhibition of Saccharomyces cerevisiae, which is uniquely able to withstand the high ethanol and low resource conditions in the end stages of fermentation. Understanding how yeast species interact with each other within the wine-fermenting community, and disentangling the importance of these ecological interactions from the environmental impacts on growth rates, is key to developing synthetic communities that can provide the sensory benefits of natural fermentation while lowering the risk of stuck ferments. While numerous studies have characterized the dynamics of experimental fermentations, carried out by both synthetic and natural communities, it is difficult to infer ecological interactions from transient population dynamics. Here, we co-culture all pairwise combinations of five commonly isolated wine-fermenting yeasts at various ethanol concentrations. We show that these pairwise outcomes are a strong function of ethanol concentration, with frequency-dependent bistable interactions common at low alcohol and an increasingly transitive competitive hierarchy developing as alcohol increases. We also show that these pairwise outcomes are predictive of five-species community outcomes, and that frequency dependence in pairwise interactions can propagate to alternative states in the full community, highlighting the importance of species abundance as well as composition. We also observe that monoculture growth rates as a function of ethanol are only weakly predictive of competitive success, highlighting the need to incorporate ecological interactions when designing synthetic communities for optimal fermentation performance.

ecology↗