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Hidden paths to endless forms most wonderful: Ecology latently shapes evolution of multicellular development in predatory bacteria

Ecological causes of developmental-system evolution, for example from predation, remain under intense investigation. An important open question is the role of latent phenotypes in eco-evo-devo. The predatory bacterium Myxococcus xanthus undergoes aggregative multicellular development upon starvation. Here we use M. xanthus to test whether evolution in several distinct growth environments that do not induce development latently alters developmental phenotypes, including morphology and plasticity, in environments that do induce development. In the MyxoEE-3 evolution experiment, growing M. xanthus populations swarmed across agar surfaces while adapting to distinct conditions varying at factors such as surface stiffness or prey identity. All examined developmental phenotypes underwent extensive and ecologically specific latent evolution, with surface stiffness, prey presence and prey identity all strongly impacting the latent evolution of development. Evolution on hard agar allowed retention of developmental proficiency and extensive stochastic phenotypic radiation, including of reaction norms, with instances of both increased plasticity and canalization. In contrast, evolution on soft agar latently led to systematic loss of development, revealing an ecologically-contingent fitness trade-off between the growth and developmental phases of a multicellular life cycle that is likely determined by details of motility behavior. Similar contingency was observed after evolution during predatory growth in distinct prey environments, with Bacillus subtilis causing greater loss of development and lower stochastic diversification than Escherichia coli. Our results have implications for understanding evolutionary interactions among predation, development and motility in myxobacterial life cycles, and, more broadly, the importance of latent phenotypes for the diversification of developmental systems.

evolutionary biology↗

Using wearable biosensors and ecological momentary assessments for the detection of prolonged stress in real life

BackgroundIncreasing efforts toward prevention of stress-related mental disorders have created a need for unobtrusive real-life monitoring of stress-related symptoms. Wearable devices have emerged as a possible solution to aid in this process, but their use in real-life stress detection has not been systematically investigated. MethodsUsing ecological momentary assessments (EMA) combined with wearable biosensors for ecological physiological assessments (EPA), we investigated the impact of an ecological stressor (i.e., an exam week) on physiological arousal and affect. With this paradigm we investigated whether we could use wearable devices to detect stress states using machine learning models. ResultsDuring stressful high-stake exam (versus control) weeks, participants reported increased negative affect and decreased positive affect. Intriguingly, physiological arousal was decreased on average during the exam week. Time-resolved analyses revealed peaks in physiological arousal associated with both self-reported stress and self-reported positive affect, while the overall decrease in physiological arousal was mediated by lower positive affect during the stress period. We then used machine learning to show that a combination of EMA and physiology yields optimal identification of stress states. ConclusionsOur findings highlight the potential of wearable biosensors in stress-related mental-health monitoring, but critically show that psychological context is essential for interpreting physiological arousal detected using these devices.

physiology↗

Individual repeatability, species differences, and the influence of socio-ecological factors on neophobia in 10 corvid species

Behavioural responses to novelty, including fear and subsequent avoidance of novel stimuli, behaviours referred to as neophobia, determine how animals interact with their environment. Neophobia aids in navigating risk and impacts on adaptability and survival. There is variation within and between individuals and species, however, lack of large-scale, comparative studies critically limits investigation of the socio-ecological drivers of neophobia. In this study, we tested responses to novel objects and food (alongside familiar food) versus a baseline (familiar food alone) in 10 corvid species (241 subjects) across 10 labs worldwide. There were species differences in the latency to touch familiar food in the novel object and food conditions relative to the baseline. Three of seven socio-ecological factors influenced object neophobia: 1) use of urban habitat (vs not), 2) territorial pair vs family group sociality and 3) large vs small flock size (whereas range, caching, hunting live animals, and genus did not); while only flock size influenced food neophobia. We found that, overall, individuals were temporally and contextually repeatable (i.e. consistent) in their novelty responses in all conditions, indicating neophobia is a stable behavioural trait. With this study, we have established a network of corvid researchers, demonstrating potential for further collaboration to explore the evolution of cognition in corvids and other bird species. These novel findings enable us, for the first time in corvids, to identify the socio-ecological correlates of neophobia and grant insight into specific elements that drive higher neophobic responses in this avian family group.

animal behavior and cognition↗

Multi-plasmid clash in a bacterial community: plasmid viability depends on the ecological setting of hosts

Plasmids are genetic elements that disperse horizontally between different strains and species of bacteria and a major factor in the dissemination of virulence factors and antibiotic resistance. Understanding the ecology of plasmids has a notable anthropocentric value and therefore the interactions between bacterial hosts and individual plasmids have been studied in detail. However, bacterial systems often carry multiple genetically distinct plasmids, but dynamics of these multiplasmid "clashes" has remained unstudied. Here, we set to investigate the survival of 11 mobilizable or conjugative plasmids in five different ecological settings. The key incentive was to determine whether plasmid dynamics are reproducible and whether there are trade-offs in plasmid fitness that stem from the ecological situation of their initial hosts. Growth rates and maximum population densities increased in all communities and treatments over the 42-day evolution experiment although plasmid contents at the end varied notably. We show that large multiresistance conferring plasmids are unfit when the community also contains smaller plasmids with fewer resistance genes. This suggests that restraining the use to few antibiotics can make bacterial communities sensitive to others. The hosts also appear to react to the presence of multiple genetically different plasmids by enhancing fimbriae production instead of alleviating costs of individual plasmids. In general, the survivors of the here-studied multi-plasmid clash are significantly affected by the presence or absence of antibiotic selection and plasmid-free hosts of varying fitness. Therefore, these trade-offs in different settings can explain for example why some resistance plasmids have an advantage during a rapid proliferation of antibiotic sensitive pathogen whereas others dominate in alternative situations.

microbiology↗

Long-distance dispersal of pigeons and doves generated new ecological opportunities for host-switching and adaptive radiation by their parasites

Adaptive radiation is an important mechanism of organismal diversification, and can be triggered by new ecological opportunities. Although poorly studied in this regard, parasites present an ideal system to study adaptive radiations because of their close associations with host species. Both experimental and comparative studies suggest that the ectoparasitic wing lice of pigeons and doves have undergone an adaptive radiation, resulting in differences in both body size and overall coloration. Here we show that long-distance dispersal by dove hosts was important for parasite diversification, providing new ecological opportunities for parasites to speciate by host-switching. We further show that these new opportunities for host-switching decreased over time, and cospeciation became the more dominant mode of parasite speciation. Taken together, our results suggest that host dispersal, followed by host-switching, provided novel ecological opportunities that facilitated adaptive radiation by parasites.

evolutionary biology↗

Ecological constraints on highly evolvable olfactory receptor genes and morphology

While evolvability of genes and traits may promote specialization during species diversification, how ecology subsequently restricts such variation remains unclear. Chemosensation requires animals to decipher a complex chemical background to locate fitness-related resources, and thus the underlying genomic architecture and morphology must cope with constant exposure to a changing odorant landscape; detecting adaptation amidst extensive chemosensory diversity is an open challenge. Phyllostomid bats, an ecologically diverse clade that evolved plant-visiting from an insectivorous ancestor, suggest the evolution of novel food detection mechanisms is a key innovation: phyllostomids behaviorally rely strongly on olfaction, while echolocation is supplemental. If this is true, exceptional variation in underlying olfactory genes and phenotypes may have preceded dietary diversification. We compared olfactory receptor (OR) genes sequenced from olfactory epithelium transcriptomes and olfactory epithelium surface area of bats with differing diets. Surprisingly, although OR evolution rates were quite variable and generally high, they are largely independent of diet. Olfactory epithelial surface area, however, is relatively larger in plant-visiting bats and there is an inverse relationship between OR evolution rates and surface area. Relatively larger surface areas suggest greater reliance on olfactory detection and stronger constraint on maintaining an already diverse OR repertoire. Instead of the typical case in which specialization and elaboration is coupled with rapid diversification of associated genes, here the relevant genes are already evolving so quickly that increased reliance on smell has led to stabilizing selection, presumably to maintain the ability to consistently discriminate among specific odorants -- a potential ecological constraint on sensory evolution. Significance StatementThe evolutionary relationship between genes and morphology is complex to decipher, and macroevolutionary trends are often measured independently; this is especially challenging to quantify in unstable genomic regions or hypervariable traits. Odorant cues are detected by proteins encoded by the largest and fasted-evolving gene family in the mammalian genome and expressed in epithelia distributed on elaborate bony structures in the nose, posing a challenge to quantification. Yet, the direct interaction of the olfactory system with environmental signals strongly suggest that selection shapes its immense diversity. In neotropical bats, where reliance on plant-visiting evolved from an insectivorous ancestor, we discovered clear dietary differences amongst species, but only after considering morphological and molecular data simultaneously, emphasizing the power of a coupled analysis.

evolutionary biology↗

Ecological and social pressures interfere with homeostatic sleep regulation in the wild

Sleep is fundamental to the health and fitness of all animals. The physiological importance of sleep is underscored by the central role of homeostasis in determining sleep investment - following periods of sleep deprivation, individuals experience longer and more intense sleep bouts. Yet, most studies of sleep have been conducted in highly controlled settings, disconnected from the ecological and social context that may exert pressures on sleep patterns in conflict with homeostatic regulation. Using tri-axial accelerometry and GPS to track the sleep patterns of a group of wild baboons (Papio anubis) at multiple temporal and spatial scales, we found that ecological and social pressures indeed interfere with homeostatic sleep regulation. Baboons sacrificed time spent sleeping when in less familiar locations and when sleeping in proximity to more group-mates, regardless of how much they had slept the prior night or how much they had physically exerted themselves the preceding day. Moreover, we found that the collective dynamics characteristic of social animal groups persist into the sleep period, as baboons exhibited synchronized patterns of waking throughout the night, particularly with nearby group-mates. Thus, for animals whose fitness depends critically on avoiding predation and developing social relationships, maintaining sleep homeostasis may be only secondary to remaining vigilant when sleeping in risky habitats and interacting with group-mates during the night. Our results highlight the importance of studying sleep in ecologically relevant contexts, where the adaptive function of sleep patterns directly reflect the complex trade-offs that have guided its evolution.

animal behavior and cognition↗

Emergent phases of ecological diversity and dynamics mapped in microcosms

Natural ecological communities display striking features, such as high biodiversity and a wide range of dynamics, that have been difficult to explain in a unified framework. Using experimental bacterial microcosms, we perform the first direct test of recent complex systems theory predicting that simple aggregate parameters dictate emergent behaviors of the community. As either the number of species or the strength of species interactions is increased, we show that microbial ecosystems transition between distinct qualitative dynamical phases in the predicted order, from a stable equilibrium where all species coexist, to partial coexistence, to emergence of persistent fluctuations in species abundance. Under the same conditions, high biodiversity and fluctuations allow and require each other. Our results demonstrate predictable emergent diversity and dynamics in ecological communities. One-Sentence SummaryA phase diagram of ecological dynamics and diversity as a function of coarse-grained features of species interaction network.

biophysics↗

The Ecology of Palm Genomes: Repeat-associated genome size expansion is constrained by aridity

O_LIGenome size varies 2,400-fold across plants, influencing their evolution through changes in cell size and cell division rates which impact plants environmental stress tolerance. Repetitive element expansion explains much genome size diversity, and the processes structuring repeat communities are analogous to those structuring ecological communities. However, which environmental stressors influence repeat community dynamics has not yet been examined from an ecological perspective. C_LIO_LIWe measured genome size and leveraged climatic data for 91% of genera within the ecologically diverse palm family (Arecaceae). We then generated genomic repeat profiles for 141 palm species, and analysed repeats using phylogenetically-informed linear models to explore relationships between repeat dynamics and environmental factors. C_LIO_LIWe show that palm genome size and repeat community composition are best explained by aridity. Specifically, EnSpm CACTA repeats were more abundant in palm species from wetter environments, which generally had larger genomes (>2.15Gbp/1C), suggesting amplification. In contrast, Ty1-copia Angela elements were more abundant in drier environments. C_LIO_LIOur results suggest water stress inhibits the expansion of repeats through selection on upper genome size limits. However, Ty1-copia Angela elements, which may associate with stress-response genes, have amplified in arid-adapted palm species. Overall, we provide novel evidence of climate influencing the assembly of repeat communities. C_LI

evolutionary biology↗

A framework for defining livestock ecotypes based on ecological modelling and exploring genomic environmental adaptation: the example of Ethiopian village chicken

In evolutionary ecology, an ecotype is a population that is genetically adapted to specific environmental conditions. Environmental and genetic characterisation of livestock ecotypes can play a crucial role in conservation and breeding improvement, particularly to achieve climate resilience. However, livestock ecotypes are often arbitrarily defined without a detailed characterisation of their agro-ecologies. In this study, we employ a novel integrated approach, combining Ecological Niche Modelling (ENM) with genomics, to delineate ecotypes based on environmental characterisation of population habitats and unravel the signatures of adaptive selection in the ecotype genomes. The method was applied on 25 Ethiopian village chicken populations representing diverse agro-climatic conditions. ENM identified six key environmental drivers of adaptation and delineated 12 ecotypes. Within- ecotype selection signature analyses (using Hp and iHS methods) identified 1,056 candidate sweep regions (SRs) associated with diverse biological processes. A few biological pathways were shared amongst most ecotypes and the involved genes showed functions important for scavenging chickens, e.g. neuronal development/processes, immune response, vision development, and learning. Genotype-environment association using Redundancy Analysis (RDA) allowed for correlating [~]33% of the SRs with major environmental drivers. Inspection of some strong candidate genes from selection signature analysis and RDA showed highly relevant functions in relation to the major environmental drivers of corresponding ecotypes. This integrated approach offers a powerful tool to gain insight into the complex processes of adaptive evolution including the genotype x environment (GxE) interactions.

genetics↗

Ecological speciation promoted by divergent regulation of functional genes within African cichlid fishes

Rapid ecological speciation along depth gradients has taken place independently and repeatedly in freshwater fishes. While the extent of genomic divergence between ecomorphs is often well understood, the molecular mechanisms facilitating such rapid diversification are typically unclear. In Lake Masoko, an East African crater lake, the cichlid Astatotilapia calliptera has diverged into shallow littoral and deep benthic ecomorphs with strikingly different jaw structures within the last 1,000 years. Using genome-wide transcriptome data from jaw tissue, we explore two major regulatory transcriptional mechanisms, expression and splicing QTL variants and examine their contribution to differential gene expression underpinning functional phenotypes. We identified 7,550 genes with significant differential expression between ecomorphs, of which 4.2% were regulated by cis-regulatory expression QTLs, and 6.4% were regulated by cis-regulatory splicing QTLs. There were also strong signals of divergent selection of differentially expressed genes that showed divergent regulation from expression, splicing or both QTL variants, including genes associated with major jaw plasticity and adaptation networks, adaptive immune system response, and oxidoreductase processes. These results suggest that transcriptome plasticity and modification have important roles during early-stage ecological speciation and demonstrate the role of regulatory-variants as important targets of selection driving ecologically-relevant divergence in gene expression that is associated with adaptive diversification.

evolutionary biology↗

Ecological insights into soil health according to the life-history traits and environment-wide associations of bacteria in agricultural soils

Soil health assessment may be enhanced by monitoring changes in bacterial populations that are indicators of various biological, physical, and chemical properties of soil. However, the lack of ecological information for many abundant bacteria in agricultural soils limits our understanding of indicator responses and, thus, their utility for guiding management. We identified bacterial indicators of twelve conventional measures of soil health, and tillage intensity, from a 16S rRNA gene-based survey of farmland across North America. We then analyzed trends according to bacterial life-history frameworks and an environment-wide association survey (EWAS) to gain ecological insights. Life-history traits were assessed using genomic traits inferred from taxonomic classifications and included: genome size, rrn copy number, and coding density. An EWAS was conducted using 89 studies of agricultural land management. Most bacterial indicators were positively correlated with biological measures and negatively correlated with physical and chemical measures of soil health, revealing broad differences in the way management shapes bacterial associations with soil health. High soil health ratings corresponded with life-history traits associated with metabolic dependency (smaller genome and lower coding density), while lower health scores corresponded with traits selected for by environmental instability and disturbance (larger genome and multiple rrn). Trade-offs in community-weighted genome size explained most variation in overall health score. EWAS confirmed the importance of disturbance-adapted bacterial indicators, underscoring the impacts of tillage on soil bacterial communities. These findings provide insights into the ecological relationships between bacterial indicators and soil health and illustrate new approaches for interpreting patterns in microbiome data.

microbiology↗

A simulation study of the ecological speciation conditions in the Galician marine snail Littorina saxatilis

In the last years the interest on evolutionary divergence at small spatial scales has increased and so did the study of speciation caused by ecologically-based divergent natural selection. The evolutionary interplay between gene flow and local adaptation can lead to low-dispersal locally adapted specialists. When this occurs the evolutionary interplay between gene flow and local adaptation could eventually lead to speciation. The L. saxatilis system consists of two ecotypes displaying a microhabitat-associated intraspecific dimorphism along the wave-exposed rocky shores of Galicia. In spite of being a well-known system, the dynamics of the ecotype formation remains unclear and cannot be studied from empirical evidence alone. In this study, individual-based simulations were used to incorporate relevant ecological, spatial and genetic information, to check different evolutionary scenarios that could evolve non-random mating preferences and finally may facilitate speciation. As main results, we observed the evolution of intermediate values of choice which matches estimates from empirical data of L. saxatilis in Galician shores and coincides with previous theoretical outcomes. Also, the use of the mating correlation as a proxy for assortative mating led to spuriously inferring greater reproductive isolation in the middle habitat than in the others, which does not happen when directly considering the choice values from the simulations. We also corroborate the well-known fact that the occurrence of speciation is influenced by the strength of selection. Taken together, this means, also according to other L. saxatilis systems, that speciation is not an immediate consequence of local divergent selection and mating preferences, but a fine tuning among several factors including the ecological conditions in the shore levels, the selection strength, the mate choice stringency and cost to choosiness. The L. saxatilis system could correspond to a case of incomplete reproductive isolation, where choice intensity is intermediate and local adaptation within the habitat is strong. These results support previous interpretations of the L. saxatilis model system and indicate that further empirical studies would be interesting to test whether the mate choice mechanism functions as a similarity-like mechanism as has been shown in other littorinids.

evolutionary biology↗

Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects

Long-term colonization of the gut microbiome by carbapenemase-producing Enterobacteriaceae (CPE) is a growing area of public health concern as it can lead to community transmission and rapid increase in cases of life-threatening CPE infections. Leveraging the observation that many subjects are decolonized without interventions within a year, we used longitudinal shotgun metagenomics (up to 12 timepoints) for detailed characterization of ecological and evolutionary dynamics in the gut microbiome of a cohort of CPE-colonized subjects and family members (n=46; 361 samples). Subjects who underwent decolonization exhibited a distinct ecological shift marked by recovery of microbial diversity, key commensals and anti-inflammatory pathways. In addition, colonization was marked by elevated but unstable Enterobacteriaceae abundances, which exhibited distinct strain-level dynamics for different species (Escherichia coli and Klebsiella pneumoniae). Finally, comparative analysis with whole genome sequencing data from CPE isolates (n=159) helped identify sub-strain variation in key functional genes and the presence of highly similar E. coli and K. pneumoniae strains with variable resistance profiles and plasmid sharing. These results provide an enhanced view into how colonization by multi-drug resistant bacteria associates with altered gut ecology and can enable transfer of resistance genes, even in the absence of overt infection and antibiotic usage.

genomics↗

The limits to ecological limits to diversification

AO_SCPLOWBSTRACTC_SCPLOWWhile the theory of micro-evolution by natural selection assigns a crucial role to competition, its role in macroevolution is less clear. Phylogenetic evidence for a decelerating accumulation of lineages suggests a feedback of lineage diversity on diversification, i.e., ecological limits to diversification. However, does this feedback only occur between close relatives, or do distant relatives also influence their diversification? In other words: are there phylogenetic limits to these ecological limits? Islands form ideal systems to answer these questions, because their boundedness facilitates an overview of all potential competitors. The DAISIE (Dynamic Assembly of Island biota through Speciation Immigration and Extinction) framework allows for testing the presence of diversity-dependence on islands given phylogenetic data on colonization and branching times. The current inference models in DAISIE assume that this diversity-dependence only applies within a colonizing clade, which we term clade-specific (CS) diversity-dependence. Here we introduce a new DAISIE model that assumes that diversity-dependence applies to all species regardless of their ancestry, i.e. diversity-dependence applies both to species within the same clade and between different clades. We call this island-wide (IW) diversity-dependence. Here we present a method to compute a likelihood for this model and develop a statistical procedure based on likelihood ratio bootstrapping to compare it to the likelihood of the CS model in order to overcome biases known for standard model selection. We apply it to the diversification of Eleutherodactylus frogs on Hispaniola. Across the Greater Antilles archipelago, this radiation shows repeated patterns of diversification in ecotypes which are similar across clades. This could be suggestive of overlapping niche space and hence between-clade interactions, i.e. IW diversity-dependence. But it could also be suggestive of only within-clade interactions, because between-clade interactions would have blocked the same ecotype re-appearing. We find that the CS model fits the data much better than the IW model, indicating that different colonizations, while resulting in similar ecotypes, are sufficiently distinct to avoid interacting strongly. We argue that non-overlapping distributions between clades (both spatially and in terms of ecotypes) cannot be used as evidence of CS diversity-dependence, because this pattern may be a consequence of IW diversity-dependence. By contrast, by using phylogenetic data rather than distributional data our method does allow for inferring the phylogenetic limits to ecological limits to diversification. We discuss how our new IW model advances our understanding also in other ways, ranging from identifying priority effects to modelling the spread of an epidemic in island-like systems, such as schools or hospitals.

evolutionary biology↗

An ecological investigation of the capacity to follow simultaneous speech and preferential detection of ones' own name

Many situations require focusing attention on one speaker, while monitoring the environment for potentially important information. Some have proposed that dividing attention among two speakers involves behavioral tradeoffs, due to limited cognitive resources. However the severity of these tradeoffs, particularly under ecologically-valid circumstances, is not well understood. We investigated the capacity to process simultaneous speech using a dual-task paradigm simulating task demands and stimuli encountered in real-life. Participants listened to conversational narratives (Narrative Stream) and monitored a stream of announcements (Barista Stream), to detect when their order was called. We measured participants performance, neural activity and skin conductance as they engaged in this dual-task. Participants achieved extremely high dual-task accuracy, with no apparent behavioral tradeoffs. Moreover, robust neural and physiological responses were observed for target-stimuli in the Barista Stream, alongside significant neural speech-tracking of the Narrative Stream. These results suggest that humans have substantial capacity to process simultaneous speech and do not suffer from insufficient processing resources, at least for this highly ecological task-combination and level of perceptual load. Results also confirmed the ecological validity of the advantage for detecting ones own name at the behavioral, neural and physiological level, highlighting the contribution of personal relevance when processing simultaneous speech.

neuroscience↗

Breakdown of cooperative architecture in dual species biofilms and the spatial ecology of predation

Adherence to surfaces and secretion of extracellular matrix, or biofilm formation, is common in the microbial world, but we often do not know how interaction at the cellular spatial scale translates to higher-order biofilm community ecology. Here we explore an especially understudied element of biofilm ecology, namely predation by the bacterium Bdellovibrio bacteriovorus. This predator can kill and consume many different Gram-negative bacteria, including Vibrio cholerae and Escherichia coli. V. cholerae can protect itself from predation within highly packed biofilm structures that it creates, whereas E. coli biofilms are highly susceptible to B. bacteriovorus. Here we explore how predator-prey dynamics change when V. cholerae and E. coli are growing in biofilms together. We find that in dual species prey biofilms, E. coli survival under B. bacteriovorus predation increases, whereas V. cholerae survival decreases. E. coli benefits from predator protection when it becomes embedded within expanding groups of highly packed V. cholerae. But we also find that the ordered, highly packed, and clonal biofilm structure of V. cholerae can be disrupted if V. cholerae cells are directly adjacent to E. coli cells at the start of biofilm growth. When this occurs, the two species become entangled, and the resulting disordered cell groups do not block predator entry. Because biofilm cell group structure depends on initial cell distributions at the start of prey biofilm growth, the colonization dynamics have a dramatic impact on the eventual multispecies biofilm architecture, which in turn determines to what extent both species survive exposure to B. bacteriovorus. Significance StatementBacteria live in multispecies, spatially structured communities ubiquitously in the natural world. These communities, or biofilms, have a strong impact on microbial ecology, but we often do not know how cellular scale interactions determine overall biofilm structure and community dynamics. Here we explore this problem in the context of predator-prey interaction, with two prey species - Vibrio cholerae and Escherichia coli - being attacked by the bacterial predator Bdellovibrio bacteriovorus. We find that when V. cholerae and E. coli grow together in biofilms, the architectures that they both produce change in ways that cannot be predicted from looking at each prey species alone, and that these changes in cell group structure impact the community dynamics of predator-prey interaction in biofilms.

microbiology↗

Distinct tumor-immune ecologies in NSCLC patientspredict progression and define a clinical biomarker of therapy response

We investigated multiplexed histological images from nine patients (both pre- and on-treatment) with immunotherapy-refractory Non-Small Cell Lung Cancer (NSCLC) treated with an oral HDAC inhibitor (vorinostat) combined with a PD-1 inhibitor (pembrolizumab). Patient responses comprised of either stable disease (SD) or progressive disease (PD). We built an extensive multiplexed-image analysis pipeline involving both cell segmentation and quadrats, coupled with spatial statistics, machine learning, and deep learning to analyze the spatial and temporal features that predict disease progression and identify potential clinical biomarkers. We found that distinct spatial immune ecologies exist between SD and PD patients. We also demonstrate that tumors from PD patients are already characterized by an immune-suppressive environment prior to treatment. Finally, we show that the learned spatial ecologies can predict disease progression better than PD-L1 status alone, suggesting these ecologies can be used as potential companion biomarkers with PD-L1 in NSCLC. These findings will be investigated in a larger-cohort study generated from an ongoing clinical trial (NCT02638090) that includes a wider range of responses including complete and partial responders. Additionally, the computational infrastructure developed in this study can be generalized to any cancer type.

cancer biology↗