Towards evolutionary predictions: Current promises and challenges

Evolutionary Applications, Год журнала: 2022, Номер 16(1), С. 3 - 21

Опубликована: Дек. 9, 2022

Abstract Evolution has traditionally been a historical and descriptive science, predicting future evolutionary processes long considered impossible. However, predictions are increasingly being developed used in medicine, agriculture, biotechnology conservation biology. Evolutionary may be for different purposes, such as to prepare the future, try change course of evolution or determine how well we understand processes. Similarly, exact aspect evolved population that want predict also differ. For example, could which genotype will dominate, fitness extinction probability population. In addition, there many uses not always recognized such. The main goal this review is increase awareness methods data research fields by showing breadth situations made. We describe diverse share common structure described predictive scope, time scale precision. Then, using examples ranging from SARS‐CoV2 influenza CRISPR‐based gene drives sustainable product formation biotechnology, discuss evolution, factors affect predictability can prevent undesirable directions promote beneficial (i.e. control). hope stimulate collaboration between establishing language predictions.

Язык: Английский

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Rapid evolution and strain turnover in the infant gut microbiome

Genome Research, Год журнала: 2022, Номер 32(6), С. 1124 - 1136

Опубликована: Май 11, 2022

Although the ecological dynamics of infant gut microbiome have been intensely studied, relatively little is known about evolutionary in microbiome. Here we analyze longitudinal fecal metagenomic data from more than 700 infants and their mothers over first year life find that microbiomes are distinct those adults. We evidence for a 10-fold increase rate evolution strain turnover compared with healthy adults, mother-infant transition at delivery being particularly dynamic period which gene loss dominates. Within few months after birth, these stabilize, gains become increasingly frequent as matures. furthermore changes show signatures seeded by mixture de novo mutations transmissions pre-evolved lineages broader family. Several occur parallel across infants, highlighting candidate genes may play important roles development Our results point to picture volatile characterized rapid change early days life.

Язык: Английский

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Understanding patterns of HIV multi-drug resistance through models of temporal and spatial drug heterogeneity

eLife, Год журнала: 2021, Номер 10

Опубликована: Сен. 2, 2021

Triple-drug therapies have transformed HIV from a fatal condition to chronic one. These should prevent drug resistance evolution, because one or more drugs suppress any partially resistant viruses. In practice, such drastically reduced, but did not eliminate, evolution. this article, we reanalyze published data an evolutionary perspective and demonstrate several intriguing patterns about evolution - evolves (1) even after years on successful therapy, (2) sequentially, often via mutation at time (3) in predictable order. We describe how these observations might emerge under two models of varying space time. Despite decades work area, much opportunity remains create with realistic parameters for three drugs, match model outcomes rates genetic individuals triple-drug therapy. Further, lessons may inform other systems.

Язык: Английский

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Elevated HIV Viral Load is Associated with Higher Recombination Rate In Vivo

Molecular Biology and Evolution, Год журнала: 2024, Номер 41(1)

Опубликована: Янв. 1, 2024

Abstract HIV’s exceptionally high recombination rate drives its intrahost diversification, enabling immune escape and multidrug resistance within people living with HIV. While we know that varies by genomic position, have little understanding of how throughout infection or between individuals as a function the cellular coinfection. We hypothesize denser populations may higher rates coinfection therefore recombination. To test this hypothesis, develop new approach (recombination analysis via time series linkage decay RATS-LD) to quantify using autocorrelation mutations across points. validate RATS-LD on simulated data under short read sequencing conditions then apply it longitudinal, high-throughput viral data, stratifying load (a proxy for density). Among sampled lowest loads (<26,800 copies/mL), estimate 1.5×10−5 events/bp/generation (95% CI: 7×10−6 2.9×10−5), similar existing estimates. However, among samples highest (>82,000 our median is approximately 6 times higher. In addition co-varying individuals, also find are associated single different Our findings suggest rather than acting constant, uniform force, can vary dynamically drastically them over time. More broadly, phenomenon affect other facultatively asexual where spatial co-localization varies.

Язык: Английский

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Study on the prediction performance of AIDS monthly incidence in Xinjiang based on time series and deep learning models

BMC Public Health, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 25, 2025

AIDS is a highly fatal infectious disease of Class B, and Xinjiang high-incidence region for in China. The core prevention control lies early monitoring warning. This study aims to identify the best model predicting monthly incidence Xinjiang, providing scientific evidence control. Monthly data from January 2004 December 2020 were collected. Six different models, including ARIMA (2,1,2) model, (2,1,2)-EGARCH (2,2) combined (2,1,2)-TGARCH (1,1) ETS (A, A, A) XGBoost LSTM used fitting forecasting. All models able capture overall trend Xinjiang. In terms RMSE MAE, performed best, achieving smallest values. For MAPE metric, best. Considering RMSE, together, was best-performing this study. also showed good predictive performance, while relatively poorly. Deep learning (such as LSTM) have significant potential time series may limitations when handling data, future improvements or combinations could enhance prediction performance.

Язык: Английский

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Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1

eLife, Год журнала: 2022, Номер 11

Опубликована: Июль 19, 2022

Infusion of broadly neutralizing antibodies (bNAbs) has shown promise as an alternative to anti-retroviral therapy against HIV. A key challenge is suppress viral escape, which more effectively achieved with a combination bNAbs. Here, we propose computational approach predict the efficacy bNAb based on population genetics HIV parametrize using high-throughput sequence data from bNAb-naive patients. By quantifying mutational target size and fitness cost HIV-1 escape bNAbs, distribution rebound times in three clinical trials. We show that cocktail bNAbs necessary optimal composition such cocktail. Our results offer rational design for HIV, how genetic can be used treatment outcomes new approaches pathogenic control.

Язык: Английский

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Soft selective sweeps: Addressing new definitions, evaluating competing models, and interpreting empirical outliers

PLoS Genetics, Год журнала: 2022, Номер 18(2), С. e1010022 - e1010022

Опубликована: Фев. 24, 2022

The ability to accurately identify and quantify genetic signatures associated with soft selective sweeps based on patterns of nucleotide variation has remained controversial. We here provide counter viewpoints recent publications in PLOS Genetics that have argued not only for the statistical identifiability sweeps, but also their pervasive evolutionary role both Drosophila HIV populations. present evidence these claims owe a lack consideration competing models, unjustified interpretations empirical outliers, as well new definitions processes themselves. Our results highlight dangers fitting models hypothesized episodic without properly first considering common and, more generally, tendency certain research areas view positive selection foregone conclusion.

Язык: Английский

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Timesweeper: accurately identifying selective sweeps using population genomic time series

Genetics, Год журнала: 2023, Номер 224(3)

Опубликована: Май 9, 2023

Despite decades of research, identifying selective sweeps, the genomic footprints positive selection, remains a core problem in population genetics. Of myriad methods that have been developed to tackle this task, few are designed leverage potential time-series data. This is because most genetic studies natural populations, only single period time can be sampled. Recent advancements sequencing technology, including improvements extracting and ancient DNA, made repeated samplings possible, allowing for more direct analysis recent evolutionary dynamics. Serial sampling organisms with shorter generation times has also become feasible due cost throughput sequencing. With these advances mind, here we present Timesweeper, fast accurate convolutional neural network-based tool sweeps data consisting multiple over time. Timesweeper analyzes by first simulating training under demographic model appropriate interest, one-dimensional network on said simulations, inferring which polymorphisms serialized set were target completed or ongoing sweep. We show simulated scenarios, identifies selected variants high resolution, estimates selection coefficients accurately than existing methods. In sum, inferences about possible when available; such will continue proliferate coming years both samples extant populations faster times, as well experimentally evolved where often generated. Methodological thus help resolve controversy role genome. provide Python package use community.

Язык: Английский

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Mutation rate, selection, and epistasis inferred from RNA virus haplotypes via neural posterior estimation

Virus Evolution, Год журнала: 2023, Номер 9(1)

Опубликована: Янв. 1, 2023

Abstract RNA viruses are particularly notorious for their high levels of genetic diversity, which is generated through the forces mutation and natural selection. However, disentangling these two a considerable challenge, this may lead to widely divergent estimates viral rates, as well difficulties in inferring fitness effects mutations. Here, we develop, test, apply an approach aimed at rate key parameters that govern selection, from haplotype sequences covering full-length genomes evolving virus population. Our employs neural posterior estimation, computational technique applies simulation-based inference with networks jointly infer multiple model parameters. We first tested our on synthetic data simulated using different rates selection while accounting sequencing errors. Reassuringly, inferred parameter were accurate unbiased. then applied serial passaging experiment MS2 bacteriophage, parasites Escherichia coli. estimated phage around 0.2 mutations per genome replication cycle (95% highest density interval: 0.051–0.56). validated finding approaches based single-locus models gave similar but much broader distributions. Furthermore, found evidence reciprocal sign epistasis between four strongly beneficial all reside stem loop controls expression lysis protein, responsible lysing host cells egress. surmise there fine balance over- underexpression leads pattern epistasis. To recap, have developed joint full errors used it reveal features governing evolution.

Язык: Английский

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Declines in prevalence alter the optimal level of sexual investment for the malaria parasite Plasmodium falciparum

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(30)

Опубликована: Июль 22, 2022

Successful infectious disease interventions can result in large reductions parasite prevalence. Such demographic change has fitness implications for individual parasites and may shift the parasite’s optimal life history strategy. Here, we explore whether declining infection rates alter Plasmodium falciparum ’s investment sexual versus asexual growth. Using a multiscale mathematical model, demonstrate how proportion of polyclonal infections, which decreases as prevalence declines, affects development strategy: Within-host competition multiclone infections favors greater growth whereas single-clone benefit from higher conversion to forms. At same time, drug treatment also imposes selection pressure on by shortening length reducing within-host competition. We assess these models using 148 P. genomes sampled French Guiana over an 18-y period intensive intervention (1998 2015). During this time frame, multiple public health measures, including introduction new drugs expanded rapid diagnostic testing, were implemented, malaria cases order magnitude. Consistent with decline, see increase relatedness among parasites, but no single clonal background grew dominate population. Analyzing allele frequency trajectories, identify genes that likely experienced selective sweeps. Supporting our model predictions, showing strongest signatures include transcription factors involved gametocyte form. These results highlight impose wide-ranging pressures affect basic traits.

Язык: Английский

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