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1.
Proc Natl Acad Sci U S A ; 120(35): e2305050120, 2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37603760

RESUMEN

Primary productivity response to climatic drivers varies temporally, indicating state-dependent interactions between climate and productivity. Previous studies primarily employed equation-based approaches to clarify this relationship, ignoring the state-dependent nature of ecological dynamics. Here, using 40 y of climate and productivity data from 48 grassland sites across Mongolia, we applied an equation-free, nonlinear time-series analysis to reveal sensitivity patterns of productivity to climate change and variability and clarify underlying mechanisms. We showed that productivity responded positively to annual precipitation in mesic regions but negatively in arid regions, with the opposite pattern observed for annual mean temperature. Furthermore, productivity responded negatively to decreasing annual aridity that integrated precipitation and temperature across Mongolia. Productivity responded negatively to interannual variability in precipitation and aridity in mesic regions but positively in arid regions. Overall, interannual temperature variability enhanced productivity. These response patterns are largely unrecognized; however, two mechanisms are inferable. First, time-delayed climate effects modify annual productivity responses to annual climate conditions. Notably, our results suggest that the sensitivity of annual productivity to increasing annual precipitation and decreasing annual aridity can even be negative when the negative time-delayed effects of annual precipitation and aridity on productivity prevail across time. Second, the proportion of plant species resistant to water and temperature stresses at a site determines the sensitivity of productivity to climate variability. Thus, we highlight the importance of nonlinear, state-dependent sensitivity of productivity to climate change and variability, accurately forecasting potential biosphere feedback to the climate system.

2.
Proc Natl Acad Sci U S A ; 120(23): e2302672120, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-37253008

RESUMEN

Across modern civilization, societal norms and rules are established and communicated largely in the form of written laws. Despite their prevalence and importance, legal documents have long been widely acknowledged to be difficult to understand for those who are required to comply with them (i.e., everyone). Why? Across two preregistered experiments, we evaluated five hypotheses for why lawyers write in a complex manner. Experiment 1 revealed that lawyers, like laypeople, were less able to recall and comprehend legal content drafted in a complex "legalese" register than content of equivalent meaning drafted in a simplified register. Experiment 2 revealed that lawyers rated simplified contracts as equally enforceable as legalese contracts, and rated simplified contracts as preferable to legalese contracts on several dimensions-including overall quality, appropriateness of style, and likelihood of being signed by a client. These results suggest that lawyers who write in a convoluted manner do so as a matter of convenience and tradition as opposed to an outright preference and that simplifying legal documents would be both tractable and beneficial for lawyers and nonlawyers alike.


Asunto(s)
Contratos , Abogados , Humanos
3.
Proc Natl Acad Sci U S A ; 120(12): e2211758120, 2023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-36930600

RESUMEN

Forecasting the response of ecological systems to environmental change is a critical challenge for sustainable management. The metabolic theory of ecology (MTE) posits scaling of biological rates with temperature, but it has had limited application to population dynamic forecasting. Here we use the temperature dependence of the MTE to constrain empirical dynamic modeling (EDM), an equation-free nonlinear machine learning approach for forecasting. By rescaling time with temperature and modeling dynamics on a "metabolic time step," our method (MTE-EDM) improved forecast accuracy in 18 of 19 empirical ectotherm time series (by 19% on average), with the largest gains in more seasonal environments. MTE-EDM assumes that temperature affects only the rate, rather than the form, of population dynamics, and that interacting species have approximately similar temperature dependence. A review of laboratory studies suggests these assumptions are reasonable, at least approximately, though not for all ecological systems. Our approach highlights how to combine modern data-driven forecasting techniques with ecological theory and mechanistic understanding to predict the response of complex ecosystems to temperature variability and trends.


Asunto(s)
Ecosistema , Modelos Biológicos , Factores de Tiempo , Temperatura , Dinámica Poblacional , Ecología
4.
Mol Cell Proteomics ; 22(12): 100658, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37806340

RESUMEN

Label-free proteomics is a fast-growing methodology to infer abundances in mass spectrometry proteomics. Extensive research has focused on spectral quantification and peptide identification. However, research toward modeling and understanding quantitative proteomics data is scarce. Here we propose a Bayesian hierarchical decision model (Baldur) to test for differences in means between conditions for proteins, peptides, and post-translational modifications. We developed a Bayesian regression model to characterize local mean-variance trends in data, to estimate measurement uncertainty and hyperparameters for the decision model. A key contribution is the development of a new gamma regression model that describes the mean-variance dependency as a mixture of a common and a latent trend-allowing for localized trend estimates. We then evaluate the performance of Baldur, limma-trend, and t test on six benchmark datasets: five total proteomics and one post-translational modification dataset. We find that Baldur drastically improves the decision in noisier post-translational modification data over limma-trend and t test. In addition, we see significant improvements using Baldur over the other methods in the total proteomics datasets. Finally, we analyzed Baldur's performance when increasing the number of replicates and found that the method always increases precision with sample size, while showing robust control of the false positive rate. We conclude that our model vastly improves over popular data analysis methods (limma-trend and t test) in several spike-in datasets by achieving a high true positive detection rate, while greatly reducing the false-positive rate.


Asunto(s)
Proteínas , Proteómica , Proteómica/métodos , Teorema de Bayes , Proteínas/química , Péptidos/metabolismo , Espectrometría de Masas/métodos
5.
Proc Natl Acad Sci U S A ; 119(32): e2203020119, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35925887

RESUMEN

Inference in neuroimaging typically occurs at the level of focal brain areas or circuits. Yet, increasingly, well-powered studies paint a much richer picture of broad-scale effects distributed throughout the brain, suggesting that many focal reports may only reflect the tip of the iceberg of underlying effects. How focal versus broad-scale perspectives influence the inferences we make has not yet been comprehensively evaluated using real data. Here, we compare sensitivity and specificity across procedures representing multiple levels of inference using an empirical benchmarking procedure that resamples task-based connectomes from the Human Connectome Project dataset (∼1,000 subjects, 7 tasks, 3 resampling group sizes, 7 inferential procedures). Only broad-scale (network and whole brain) procedures obtained the traditional 80% statistical power level to detect an average effect, reflecting >20% more statistical power than focal (edge and cluster) procedures. Power also increased substantially for false discovery rate- compared with familywise error rate-controlling procedures. The downsides are fairly limited; the loss in specificity for broad-scale and FDR procedures was relatively modest compared to the gains in power. Furthermore, the broad-scale methods we introduce are simple, fast, and easy to use, providing a straightforward starting point for researchers. This also points to the promise of more sophisticated broad-scale methods for not only functional connectivity but also related fields, including task-based activation. Altogether, this work demonstrates that shifting the scale of inference and choosing FDR control are both immediately attainable and can help remedy the issues with statistical power plaguing typical studies in the field.


Asunto(s)
Conectoma , Imagen por Resonancia Magnética , Encéfalo/fisiología , Conectoma/métodos , Humanos , Imagen por Resonancia Magnética/métodos
6.
Proc Natl Acad Sci U S A ; 119(26): e2102466119, 2022 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-35733249

RESUMEN

Severe deterioration of water quality in lakes, characterized by overabundance of algae and declining dissolved oxygen in the deep lake (DOB), was one of the ecological crises of the 20th century. Even with large reductions in phosphorus loading, termed "reoligotrophication," DOB and chlorophyll (CHL) have often not returned to their expected pre-20th-century levels. Concurrently, management of lake health has been confounded by possible consequences of climate change, particularly since the effects of climate are not neatly separable from the effects of eutrophication. Here, using Lake Geneva as an iconic example, we demonstrate a complementary alternative to parametric models for understanding and managing lake systems. This involves establishing an empirically-driven baseline that uses supervised machine learning to capture the changing interdependencies among biogeochemical variables and then combining the empirical model with a more conventional equation-based model of lake physics to predict DOB over decadal time-scales. The hybrid model not only leads to substantially better forecasts, but also to a more actionable description of the emergent rates and processes (biogeochemical, ecological, etc.) that drive water quality. Notably, the hybrid model suggests that the impact of a moderate 3°C air temperature increase on water quality would be on the same order as the eutrophication of the previous century. The study provides a template and a practical path forward to cope with shifts in ecology to manage environmental systems for non-analogue futures.


Asunto(s)
Lagos , Calidad del Agua , Ecosistema , Monitoreo del Ambiente , Eutrofización , Lagos/química , Fósforo/análisis , Suiza
7.
Proc Natl Acad Sci U S A ; 119(46): e2207609119, 2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36343229

RESUMEN

Understanding the role of climate change, resource availability, and population growth in human mobility remains critically important in anthropology. Researching linkages between climate and demographic changes during the short settlement history of Aotearoa (New Zealand) requires temporal precision equivalent to the period of a single generation. However, current modeling approaches frequently use small terrestrial radiocarbon datasets, a practice that obscures past Maori population patterns and their connection to changing climate. Our systematic analysis of terrestrial and marine 14C ages has enabled robust assessments of the largest dataset yet collated from island contexts. This analysis has been made possible by the recent development of a temporal marine correction for southern Pacific waters, and our findings show the shortcomings of previous models. We demonstrate that human settlement in the mid to late 13th century AD is unambiguous. We highlight initial (AD 1250 to 1275) settlement in the North Island. The South Island was reached a decade later (AD 1280 to 1295), where the hunting of giant flightless moa commenced (AD 1300 to 1415), and the population grew rapidly. Population growth leveled off around AD 1340 and declined between AD 1380 and 1420, synchronous with the onset of the Little Ice Age and moa loss as an essential food source. The population continued to grow in the more economically stable north, where conditions for horticulture were optimal. The enhanced precision of this research afforded by the robust analysis of marine dates opens up unique opportunities to investigate interconnectivity in Polynesia and inform the patterns seen in other island contexts.


Asunto(s)
Cambio Climático , Nativos de Hawái y Otras Islas del Pacífico , Humanos , Nueva Zelanda , Crecimiento Demográfico , Antropología
8.
Proc Natl Acad Sci U S A ; 119(36): e2118539119, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-36037344

RESUMEN

Ecological interactions are not uniform across time and can vary with environmental conditions. Yet, interactions among species are often measured with short-term controlled experiments whose outcomes can depend greatly on the particular environmental conditions under which they are performed. As an alternative, we use empirical dynamic modeling to estimate species interactions across a wide range of environmental conditions directly from existing long-term monitoring data. In our case study from a southern California kelp forest, we test whether interactions between multiple kelp and sea urchin species can be reliably reconstructed from time-series data and whether those interactions vary predictably in strength and direction across observed fluctuations in temperature, disturbance, and low-frequency oceanographic regimes. We show that environmental context greatly alters the strength and direction of species interactions. In particular, the state of the North Pacific Gyre Oscillation seems to drive the competitive balance between kelp species, asserting bottom-up control on kelp ecosystem dynamics. We show the importance of specifically studying variation in interaction strength, rather than mean interaction outcomes, when trying to understand the dynamics of complex ecosystems. The significant context dependency in species interactions found in this study argues for a greater utilization of long-term data and empirical dynamic modeling in studies of the dynamics of other ecosystems.


Asunto(s)
Ecosistema , Kelp , Modelos Biológicos , Animales , Bosques , Océano Pacífico , Erizos de Mar , Temperatura , Movimientos del Agua
9.
BMC Bioinformatics ; 25(1): 147, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605284

RESUMEN

BACKGROUND: Expression quantitative trait locus (eQTL) analysis aims to detect the genetic variants that influence the expression of one or more genes. Gene-level eQTL testing forms a natural grouped-hypothesis testing strategy with clear biological importance. Methods to control family-wise error rate or false discovery rate for group testing have been proposed earlier, but may not be powerful or easily apply to eQTL data, for which certain structured alternatives may be defensible and may enable the researcher to avoid overly conservative approaches. RESULTS: In an empirical Bayesian setting, we propose a new method to control the false discovery rate (FDR) for grouped hypotheses. Here, each gene forms a group, with SNPs annotated to the gene corresponding to individual hypotheses. The heterogeneity of effect sizes in different groups is considered by the introduction of a random effects component. Our method, entitled Random Effects model and testing procedure for Group-level FDR control (REG-FDR), assumes a model for alternative hypotheses for the eQTL data and controls the FDR by adaptive thresholding. As a convenient alternate approach, we also propose Z-REG-FDR, an approximate version of REG-FDR, that uses only Z-statistics of association between genotype and expression for each gene-SNP pair. The performance of Z-REG-FDR is evaluated using both simulated and real data. Simulations demonstrate that Z-REG-FDR performs similarly to REG-FDR, but with much improved computational speed. CONCLUSION: Our results demonstrate that the Z-REG-FDR method performs favorably compared to other methods in terms of statistical power and control of FDR. It can be of great practical use for grouped hypothesis testing for eQTL analysis or similar problems in statistical genomics due to its fast computation and ability to be fit using only summary data.


Asunto(s)
Genómica , Sitios de Carácter Cuantitativo , Simulación por Computador , Teorema de Bayes , Genotipo
10.
Genet Epidemiol ; 47(1): 45-60, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36116031

RESUMEN

Populations of non-European ancestry are substantially underrepresented in genome-wide association studies (GWAS). As genetic effects can differ between ancestries due to possibly different causal variants or linkage disequilibrium patterns, a meta-analysis that includes GWAS of all populations yields biased estimation in each of the populations and the bias disproportionately impacts non-European ancestry populations. This is because meta-analysis combines study-specific estimates with inverse variance as the weights, which causes biases towards studies with the largest sample size, typical of the European ancestry population. In this paper, we propose two empirical Bayes (EB) estimators to borrow the strength of information across populations although accounting for between-population heterogeneity. Extensive simulation studies show that the proposed EB estimators are largely unbiased and improve efficiency compared to the population-specific estimator. In contrast, even though the meta-analysis estimator has a much smaller variance, it yields significant bias when the genetic effect is heterogeneous across populations. We apply the proposed EB estimators to a large-scale trans-ancestry GWAS of stroke and demonstrate that the EB estimators reduce the variance of the population-specific estimator substantially, with the effect estimates close to the population-specific estimates.


Asunto(s)
Estudio de Asociación del Genoma Completo , Modelos Genéticos , Humanos , Teorema de Bayes , Simulación por Computador , Desequilibrio de Ligamiento
11.
Neuroimage ; 289: 120540, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38355076

RESUMEN

INTRODUCTION: Functional brain networks (FBNs) coordinate brain functions and are studied in fMRI using blood-oxygen-level-dependent (BOLD) signal correlations. Previous research links FBN changes to aging and cognitive decline, but various physiological factors influnce BOLD signals. Few studies have investigated the intrinsic components of the BOLD signal in different timescales using signal decomposition. This study aimed to explore differences between intrinsic FBNs and traditional BOLD-FBN, examining their associations with age and cognitive performance in a healthy cohort without dementia. MATERIALS AND METHODS: A total of 396 healthy participants without dementia (men = 157; women = 239; age range = 20-85 years) were enrolled in this study. The BOLD signal was decomposed into several intrinsic signals with different timescales using ensemble empirical mode decomposition, and FBNs were constructed based on both the BOLD and intrinsic signals. Subsequently, network features-global efficiency and local efficiency values-were estimated to determine their relationship with age and cognitive performance. RESULTS: The findings revealed that the global efficiency of traditional BOLD-FBN correlated significantly with age, with specific intrinsic FBNs contributing to these correlations. Moreover, local efficiency analysis demonstrated that intrinsic FBNs were more meaningful than traditional BOLD-FBN in identifying brain regions related to age and cognitive performance. CONCLUSIONS: These results underscore the importance of exploring timescales of BOLD signals when constructing FBN and highlight the relevance of specific intrinsic FBNs to aging and cognitive performance. Consequently, this decomposition-based FBN-building approach may offer valuable insights for future fMRI studies.


Asunto(s)
Mapeo Encefálico , Demencia , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Mapeo Encefálico/métodos , Encéfalo/fisiología , Envejecimiento/fisiología , Imagen por Resonancia Magnética/métodos , Cognición/fisiología
12.
Eur J Neurosci ; 59(11): 3093-3116, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38616566

RESUMEN

The amygdala (AMY) is widely implicated in fear learning and fear behaviour, but it remains unclear how the many biological components present within AMY interact to achieve these abilities. Building on previous work, we hypothesize that individual AMY nuclei represent different quantities and that fear conditioning arises from error-driven learning on the synapses between AMY nuclei. We present a computational model of AMY that (a) recreates the divisions and connections between AMY nuclei and their constituent pyramidal and inhibitory neurons; (b) accommodates scalable high-dimensional representations of external stimuli; (c) learns to associate complex stimuli with the presence (or absence) of an aversive stimulus; (d) preserves feature information when mapping inputs to salience estimates, such that these estimates generalize to similar stimuli; and (e) induces a diverse profile of neural responses within each nucleus. Our model predicts (1) defensive responses and neural activities in several experimental conditions, (2) the consequence of artificially ablating particular nuclei and (3) the tendency to generalize defensive responses to novel stimuli. We test these predictions by comparing model outputs to neural and behavioural data from animals and humans. Despite the relative simplicity of our model, we find significant overlap between simulated and empirical data, which supports our claim that the model captures many of the neural mechanisms that support fear conditioning. We conclude by comparing our model to other computational models and by characterizing the theoretical relationship between pattern separation and fear generalization in healthy versus anxious individuals.


Asunto(s)
Amígdala del Cerebelo , Extinción Psicológica , Miedo , Generalización Psicológica , Modelos Neurológicos , Miedo/fisiología , Amígdala del Cerebelo/fisiología , Extinción Psicológica/fisiología , Humanos , Animales , Generalización Psicológica/fisiología , Condicionamiento Clásico/fisiología , Neuronas/fisiología , Potenciales de Acción/fisiología
13.
Hum Brain Mapp ; 45(10): e26782, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38989630

RESUMEN

This study assesses the reliability of resting-state dynamic causal modelling (DCM) of magnetoencephalography (MEG) under conductance-based canonical microcircuit models, in terms of both posterior parameter estimates and model evidence. We use resting-state MEG data from two sessions, acquired 2 weeks apart, from a cohort with high between-subject variance arising from Alzheimer's disease. Our focus is not on the effect of disease, but on the reliability of the methods (as within-subject between-session agreement), which is crucial for future studies of disease progression and drug intervention. To assess the reliability of first-level DCMs, we compare model evidence associated with the covariance among subject-specific free energies (i.e., the 'quality' of the models) with versus without interclass correlations. We then used parametric empirical Bayes (PEB) to investigate the differences between the inferred DCM parameter probability distributions at the between subject level. Specifically, we examined the evidence for or against parameter differences (i) within-subject, within-session, and between-epochs; (ii) within-subject between-session; and (iii) within-site between-subjects, accommodating the conditional dependency among parameter estimates. We show that for data acquired close in time, and under similar circumstances, more than 95% of inferred DCM parameters are unlikely to differ, speaking to mutual predictability over sessions. Using PEB, we show a reciprocal relationship between a conventional definition of 'reliability' and the conditional dependency among inferred model parameters. Our analyses confirm the reliability and reproducibility of the conductance-based DCMs for resting-state neurophysiological data. In this respect, the implicit generative modelling is suitable for interventional and longitudinal studies of neurological and psychiatric disorders.


Asunto(s)
Enfermedad de Alzheimer , Magnetoencefalografía , Humanos , Magnetoencefalografía/métodos , Magnetoencefalografía/normas , Reproducibilidad de los Resultados , Enfermedad de Alzheimer/fisiopatología , Masculino , Femenino , Anciano , Modelos Neurológicos , Teorema de Bayes
14.
Biostatistics ; 24(2): 406-424, 2023 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-34269371

RESUMEN

It is becoming increasingly common for researchers to consider incorporating external information from large studies to improve the accuracy of statistical inference instead of relying on a modestly sized data set collected internally. With some new predictors only available internally, we aim to build improved regression models based on individual-level data from an "internal" study while incorporating summary-level information from "external" models. We propose a meta-analysis framework along with two weighted estimators as the composite of empirical Bayes estimators, which combines the estimates from different external models. The proposed framework is flexible and robust in the ways that (i) it is capable of incorporating external models that use a slightly different set of covariates; (ii) it is able to identify the most relevant external information and diminish the influence of information that is less compatible with the internal data; and (iii) it nicely balances the bias-variance trade-off while preserving the most efficiency gain. The proposed estimators are more efficient than the naïve analysis of the internal data and other naïve combinations of external estimators.


Asunto(s)
Modelos Estadísticos , Humanos , Teorema de Bayes , Interpretación Estadística de Datos , Sesgo
15.
BMC Med ; 22(1): 112, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38475826

RESUMEN

BACKGROUND: The transitivity assumption is the cornerstone of network meta-analysis (NMA). Violating transitivity compromises the credibility of the indirect estimates and, by extent, the estimated treatment effects of the comparisons in the network. The present study offers comprehensive empirical evidence on the completeness of reporting and evaluating transitivity in systematic reviews with multiple interventions. METHODS: We screened the datasets of two previous empirical studies, resulting in 361 systematic reviews with NMA published between January 2011 and April 2015. We updated our evidence base with an additional 360 systematic reviews with NMA published between 2016 and 2021, employing a pragmatic approach. We devised assessment criteria for reporting and evaluating transitivity using relevant methodological literature and compared their reporting frequency before and after the PRISMA-NMA statement. RESULTS: Systematic reviews published after PRISMA-NMA were more likely to provide a protocol (odds ratio (OR): 3.94, 95% CI: 2.79-5.64), pre-plan the transitivity evaluation (OR: 3.01, 95% CI: 1.54-6.23), and report the evaluation and results (OR: 2.10, 95% CI: 1.55-2.86) than those before PRISMA-NMA. However, systematic reviews after PRISMA-NMA were less likely to define transitivity (OR: 0.57, 95% CI: 0.42-0.79) and discuss the implications of transitivity (OR: 0.48, 95% CI: 0.27-0.85) than those published before PRISMA-NMA. Most systematic reviews evaluated transitivity statistically than conceptually (40% versus 12% before PRISMA-NMA, and 54% versus 11% after PRISMA-NMA), with consistency evaluation being the most preferred (34% before versus 47% after PRISMA-NMA). One in five reviews inferred the plausibility of the transitivity (22% before versus 18% after PRISMA-NMA), followed by 11% of reviews that found it difficult to judge transitivity due to insufficient data. In justifying their conclusions, reviews considered mostly the comparability of the trials (24% before versus 30% after PRISMA-NMA), followed by the consistency evaluation (23% before versus 16% after PRISMA-NMA). CONCLUSIONS: Overall, there has been a slight improvement in reporting and evaluating transitivity since releasing PRISMA-NMA, particularly in items related to the systematic review report. Nevertheless, there has been limited attention to pre-planning the transitivity evaluation and low awareness of the conceptual evaluation methods that align with the nature of the assumption.


Asunto(s)
Informe de Investigación , Humanos , Metaanálisis en Red
16.
Brief Bioinform ; 23(1)2022 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-34849574

RESUMEN

Spatial transcriptomics has been emerging as a powerful technique for resolving gene expression profiles while retaining tissue spatial information. These spatially resolved transcriptomics make it feasible to examine the complex multicellular systems of different microenvironments. To answer scientific questions with spatial transcriptomics and expand our understanding of how cell types and states are regulated by microenvironment, the first step is to identify cell clusters by integrating the available spatial information. Here, we introduce SC-MEB, an empirical Bayes approach for spatial clustering analysis using a hidden Markov random field. We have also derived an efficient expectation-maximization algorithm based on an iterative conditional mode for SC-MEB. In contrast to BayesSpace, a recently developed method, SC-MEB is not only computationally efficient and scalable to large sample sizes but is also capable of choosing the smoothness parameter and the number of clusters. We performed comprehensive simulation studies to demonstrate the superiority of SC-MEB over some existing methods. We applied SC-MEB to analyze the spatial transcriptome of human dorsolateral prefrontal cortex tissues and mouse hypothalamic preoptic region. Our analysis results showed that SC-MEB can achieve a similar or better clustering performance to BayesSpace, which uses the true number of clusters and a fixed smoothness parameter. Moreover, SC-MEB is scalable to large 'sample sizes'. We then employed SC-MEB to analyze a colon dataset from a patient with colorectal cancer (CRC) and COVID-19, and further performed differential expression analysis to identify signature genes related to the clustering results. The heatmap of identified signature genes showed that the clusters identified using SC-MEB were more separable than those obtained with BayesSpace. Using pathway analysis, we identified three immune-related clusters, and in a further comparison, found the mean expression of COVID-19 signature genes was greater in immune than non-immune regions of colon tissue. SC-MEB provides a valuable computational tool for investigating the structural organizations of tissues from spatial transcriptomic data.


Asunto(s)
Algoritmos , COVID-19/metabolismo , Simulación por Computador , Perfilación de la Expresión Génica , SARS-CoV-2/metabolismo , Animales , Colon/metabolismo , Neoplasias Colorrectales/metabolismo , Corteza Prefontal Dorsolateral/metabolismo , Humanos , Hipotálamo/metabolismo , Cadenas de Markov , Ratones
17.
Mol Ecol ; 33(2): e17211, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37996993

RESUMEN

Hybrid zones among mussel species have been extensively studied in the northern hemisphere. In South America, it has only recently become possible to study the natural hybrid zones, due to the clarification of the taxonomy of native mussels of the Mytilus genus. Analysing 54 SNP markers, we show the genetic species composition and admixture in the hybrid zone between M. chilensis and M. platensis in the southern end of South America. Bayesian, non-Bayesian clustering and re-assignment algorithms showed that the natural hybrid zone between M. chilensis and M. platensis in the Strait of Magellan, Isla Grande de Tierra del Fuego and the Falkland Islands shows clinal architecture. The hybrid zone can be divided into three different areas: the first one is on the Atlantic coast where only pure M. platensis and hybrid were found. In the second one, inside the Strait of Magellan, pure individuals of both species and mussels with variable degrees of hybridisation coexist. In the last area at the Strait in front of Punta Arenas City, fjords on the Isla Grande de Tierra del Fuego, and at the Beagle Channel, only M. chilensis and a low number of hybrids were found. According to the proportion of hybrids, bays with protected conditions away from strong currents would give better conditions for hybridisation. We do not find evidence of any other mussel species such as M. edulis, M. galloprovincialis, M. planulatus or M. trossulus in the zone.


Asunto(s)
Mytilus , Humanos , Animales , Perros , Mytilus/genética , Islas Malvinas , Teorema de Bayes , Genotipo , América del Sur
18.
Mol Ecol ; : e17451, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970417

RESUMEN

Human-mediated habitat destruction has had a profound impact on increased species extinction rates and population declines worldwide. The coastal development in the United Arab Emirates (UAE) over the last two decades, serves as an example of how habitat transformation can alter the landscape of a country in just a few years. Here, we study the genomic implications of habitat transformation in the Critically Endangered Emirati Leaf-toed Gecko (Asaccus caudivolvulus), the only endemic vertebrate of the UAE. We generate a high-quality reference genome for this gecko, representing the first reference genome for the family Phyllodactylidae, and produce whole-genome resequencing data for 23 specimens from 10 different species of leaf-toed geckos. Our results show that A. caudivolvulus has consistently lower genetic diversity than any other Arabian species of Asaccus, suggesting a history of ancient population declines. However, high levels of recent inbreeding are recorded among populations in heavily developed areas, with a more than 50% increase in long runs of homozygosity within a 9-year period. Moreover, results suggest that this species does not effectively purge deleterious mutations, hence making it more vulnerable to future stochastic threats. Overall, results show that A. caudivolvulus is in urgent need of protection, and habitat preservation must be warranted to ensure the species' survival.

19.
Mol Ecol ; 33(14): e17436, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38872589

RESUMEN

Even seemingly homogeneous on the surface, the oceans display high environmental heterogeneity across space and time. Indeed, different soft barriers structure the marine environment, which offers an appealing opportunity to study various evolutionary processes such as population differentiation and speciation. Here, we focus on Amphiprion clarkii (Actinopterygii; Perciformes), the most widespread of clownfishes that exhibits the highest colour polymorphism. Clownfishes can only disperse during a short pelagic larval phase before their sedentary adult lifestyle, which might limit connectivity among populations, thus facilitating speciation events. Consequently, the taxonomic status of A. clarkii has been under debate. We used whole-genome resequencing data of 67 A. clarkii specimens spread across the Indian and Pacific Oceans to characterize the species' population structure, demographic history and colour polymorphism. We found that A. clarkii spread from the Indo-Pacific Ocean to the Pacific and Indian Oceans following a stepping-stone dispersal and that gene flow was pervasive throughout its demographic history. Interestingly, colour patterns differed noticeably among the Indonesian populations and the two populations at the extreme of the sampling distribution (i.e. Maldives and New Caledonia), which exhibited more comparable colour patterns despite their geographic and genetic distances. Our study emphasizes how whole-genome studies can uncover the intricate evolutionary past of wide-ranging species with diverse phenotypes, shedding light on the complex nature of the species concept paradigm.


Asunto(s)
Flujo Génico , Genética de Población , Perciformes , Animales , Perciformes/genética , Perciformes/clasificación , Océano Pacífico , Pigmentación/genética , Océano Índico , Evolución Biológica , Secuenciación Completa del Genoma , Color
20.
Mol Ecol ; 33(9): e17346, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38581173

RESUMEN

Wildlife populations are becoming increasingly fragmented by anthropogenic development. Small and isolated populations often face an elevated risk of extinction, in part due to inbreeding depression. Here, we examine the genomic consequences of urbanization in a caracal (Caracal caracal) population that has become isolated in the Cape Peninsula region of the City of Cape Town, South Africa, and is thought to number ~50 individuals. We document low levels of migration into the population over the past ~75 years, with an estimated rate of 1.3 effective migrants per generation. As a consequence of this isolation and small population size, levels of inbreeding are elevated in the contemporary Cape Peninsula population (mean FROH = 0.20). Inbreeding primarily manifests as long runs of homozygosity >10 Mb, consistent with the effects of isolation due to the rapid recent growth of Cape Town. To explore how reduced migration and elevated inbreeding may impact future population dynamics, we parameterized an eco-evolutionary simulation model. We find that if migration rates do not change in the future, the population is expected to decline, though with a low projected risk of extinction. However, if migration rates decline or anthropogenic mortality rates increase, the potential risk of extinction is greatly elevated. To avert a population decline, we suggest that translocating migrants into the Cape Peninsula to initiate a genetic rescue may be warranted in the near future. Our analysis highlights the utility of genomic datasets coupled with computational simulation models for investigating the influence of gene flow on population viability.


Asunto(s)
Flujo Génico , Genética de Población , Endogamia , Dinámica Poblacional , Animales , Sudáfrica , Densidad de Población , Urbanización , Migración Animal
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