Innate immunity decreases pathogen diversity during infection DOI Creative Commons
Jonathan C. Kagan

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(40)

Опубликована: Сен. 20, 2023

With advancements in stem cell technology, vitro models using iPSC (induced pluripotent cells)-derived cardiomyocytes (iPSC-CM) and engineered heart tissues (EHT) can serve as powerful tools for disease modeling drug screening. ...Fluorescent reporters of cardiac electrophysiology provide valuable information on tissue function. However, motion artifacts caused by muscle contraction interfere with accurate measurement fluorescence signals. Although drugs ...

Язык: Английский

The Effects of Mutation and Recombination Rate Heterogeneity on the Inference of Demography and the Distribution of Fitness Effects DOI Creative Commons
Vivak Soni, Susanne P. Pfeifer, Jeffrey D. Jensen

и другие.

Genome Biology and Evolution, Год журнала: 2024, Номер 16(2)

Опубликована: Янв. 11, 2024

Abstract Disentangling the effects of demography and selection has remained a focal point population genetic analysis. Knowledge about mutation recombination is essential in this endeavor; however, despite clear evidence that both rates vary across genomes, it common practice to model as fixed. In study, we quantify how unaccounted for rate heterogeneity may impact inference using approaches inferring (DFE-alpha, Grapes, polyDFE) and/or (fastsimcoal2 δaδi). We demonstrate that, if not properly modeled, can increase uncertainty estimation demographic selective parameters some scenarios result mis-leading inference. These results highlight importance quantifying fundamental evolutionary before utilizing genomic data drift (i.e. modulated by history) selection; or, at least, these should be directly modeled downstream

Язык: Английский

Процитировано

9

A whole-genome scan for evidence of recent positive and balancing selection in aye-ayes (Daubentonia madagascariensis) utilizing a well-fit evolutionary baseline model DOI Creative Commons
Vivak Soni, John W. Terbot, Cyril J. Versoza

и другие.

Опубликована: Ноя. 11, 2024

The aye-aye (

Язык: Английский

Процитировано

8

Inferring the demographic history of aye-ayes (Daubentonia madagascariensis) from high-quality, whole-genome, population-level data DOI Creative Commons
John W. Terbot, Vivak Soni, Cyril J. Versoza

и другие.

Опубликована: Ноя. 11, 2024

The nocturnal aye-aye,

Язык: Английский

Процитировано

7

Inferring the demographic history of aye-ayes (Daubentonia madagascariensis) from high-quality, whole-genome, population-level data DOI Creative Commons
John W. Terbot, Vivak Soni, Cyril J. Versoza

и другие.

Genome Biology and Evolution, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Abstract The nocturnal aye-aye, Daubentonia madagascariensis, is one of the most elusive lemurs on island Madagascar. timing its activity and arboreal lifestyle has generally made it difficult to obtain accurate assessments population size using traditional census methods. Therefore, alternative estimates provided by genetic inference are essential for yielding much needed information conservation measures enabling ecological evolutionary studies this species. Here, we utilize genomic data from 17 individuals—including 5 newly sequenced, high-coverage genomes—to estimate history. Essential estimation recently published annotations aye-aye genome which allow variation at putatively neutral regions be included in procedures, subject selective constraints, or linkage such sites, excluded owing biasing effects selection demographic inference. By comparing a variety tools develop well-supported model history, find strong support two demes, separating northern Madagascar rest island. Additionally, that experienced severe reductions size. first occurred rapidly, approximately 3,000 5,000 years ago, likely corresponded with arrival humans second over past few decades related substantial habitat loss, suggesting species still undergoing decline remains great risk extinction.

Язык: Английский

Процитировано

1

Evaluating power to detect recurrent selective sweeps under increasingly realistic evolutionary null models DOI
Vivak Soni, Parul Johri, Jeffrey D. Jensen

и другие.

Evolution, Год журнала: 2023, Номер 77(10), С. 2113 - 2127

Опубликована: Июнь 30, 2023

The detection of selective sweeps from population genomic data often relies on the premise that beneficial mutations in question have fixed very near sampling time. As it has been previously shown power to detect a sweep is strongly dependent time since fixation as well strength selection, naturally case strong, recent leave strongest signatures. However, biological reality enter populations at rate, one partially determines mean wait between events and hence their age distribution. An important thus remains about recurrent when they are modeled by realistic mutation rate part distribution fitness effects, opposed single, recent, isolated event purely neutral background more commonly modeled. Here we use forward-in-time simulations study performance used statistics, within context evolutionary baseline models incorporating purifying size change, recombination heterogeneity. Results demonstrate interplay these processes, necessitating caution interpreting selection scans; specifically, false-positive rates excess true-positive across much evaluated parameter space, undetectable unless exceptionally strong.

Язык: Английский

Процитировано

15

Temporal challenges in detecting balancing selection from population genomic data DOI Creative Commons
Vivak Soni, Jeffrey D. Jensen

G3 Genes Genomes Genetics, Год журнала: 2024, Номер 14(6)

Опубликована: Март 29, 2024

Abstract The role of balancing selection in maintaining genetic variation remains an open question population genetics. Recent years have seen numerous studies identifying candidate loci potentially experiencing selection, most predominantly human populations. There are however alternative evolutionary processes that may leave similar patterns variation, thereby confounding inference, and the expected signatures additionally change a temporal fashion. Here we use forward-in-time simulations to quantify statistical power detect using both site frequency spectrum- linkage disequilibrium-based methods under variety evolutionarily realistic null models. We find whilst spectrum-based little immediately after balanced mutation begins segregating, increases with time since introduction allele. Conversely, considerable allele is young, dissipates rapidly as increases. Taken together, this suggests effective at detecting long-term (>25N generations allele) over much shorter timescales (<1N generations), leaving large frame which current action selection. Finally, investigate extent mimic these patterns, demonstrate need for caution attempting distinguish from those neutral (e.g. structure admixture) well selective partial sweeps).

Язык: Английский

Процитировано

6

Inferring demographic and selective histories from population genomic data using a two-step approach in species with coding-sparse genomes: an application to human data DOI Creative Commons
Vivak Soni, Jeffrey D. Jensen

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 22, 2024

The demographic history of a population, and the distribution fitness effects (DFE) newly arising mutations in functional genomic regions, are fundamental factors dictating both genetic variation evolutionary trajectories. Although DFE inference has been performed extensively humans, these approaches have generally either limited to simple models involving single or, where complex population inferred, without accounting for potentially confounding selection at linked sites. Taking advantage coding-sparse nature genome, we propose 2-step approach which coalescent simulations first used infer multi-population model, utilizing large non-functional regions that likely free from background selection. We then use forward-in-time perform conditional on demography inferred expected estimation procedure. Throughout, recombination mutation rate maps were account underlying empirical heterogeneity across human genome. Importantly, within this framework it is possible utilize fit multiple aspects data, scheme represents generalized such large-scale species with genomes.

Язык: Английский

Процитировано

6

Population genetic considerations regarding the interpretation of within-patient SARS-CoV-2 polymorphism data DOI Creative Commons
Vivak Soni, John W. Terbot, Jeffrey D. Jensen

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 16, 2024

Язык: Английский

Процитировано

5

A Simulation Framework for Modeling the Within-Patient Evolutionary Dynamics of SARS-CoV-2 DOI Creative Commons
John W. Terbot, Brandon S. Cooper, Jeffrey M. Good

и другие.

Genome Biology and Evolution, Год журнала: 2023, Номер 15(11)

Опубликована: Ноя. 1, 2023

Abstract The global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to considerable interest in detecting novel beneficial mutations and other genomic changes that may signal the development variants concern (VOCs). ability accurately detect these within individual patient samples is important enabling early detection VOCs. Such scans for rarely acting positive selection are best performed via comparison empirical data with simulated wherein commonly evolutionary factors, including mutation recombination, reproductive infection dynamics, purifying background selection, can be carefully accounted parameterized. Although there been work quantify factors SARS-CoV-2, they have yet integrated into a baseline model describing intrahost dynamics. To construct such model, we develop simulation framework enables one establish expectations underlying levels patterns patient-level variation. By varying eight key parameters, evaluated 12,096 different model–parameter combinations compared them existing data. Of these, 592 models (∼5%) were plausible based on resulting mean expected number segregating variants. These shared several commonalities shedding light SARS-CoV-2 dynamics: bottlenecks, low skew, distribution fitness effects skewed toward strongly deleterious mutations. We also describe areas uncertainty highlight additional sequence help further refine model. This study lays groundwork improved analysis future within-patient

Язык: Английский

Процитировано

6

Biases in ARG-based inference of historical population size in populations experiencing selection DOI Creative Commons
Jacob I. Marsh, Parul Johri

Molecular Biology and Evolution, Год журнала: 2024, Номер 41(7)

Опубликована: Июнь 14, 2024

Inferring the demographic history of populations provides fundamental insights into species dynamics and is essential for developing a null model to accurately study selective processes. However, background selection sweeps can produce genomic signatures at linked sites that mimic or mask signals associated with historical population size change. While theoretical biases introduced by effects have been well established, it unclear whether ancestral recombination graph (ARG)-based approaches inference in typical empirical analyses are susceptible misinference due these effects. To address this, we developed highly realistic forward simulations human Drosophila melanogaster populations, including empirically estimated variability gene density, mutation rates, purifying, positive selection, across different scenarios, broadly assess impact on using genealogy-based approach. Our results indicate minimally although could cause similar genome architecture parameters experiencing more frequent recurrent sweeps. We found accurate D. ARG-based methods compromised presence pervasive alone, leading spurious inferences recent expansion, which may be further worsened sweeps, depending proportion strength beneficial mutations. Caution additional testing species-specific needed when inferring non-human avoid selection.

Язык: Английский

Процитировано

2