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Sequencing pools of individuals rather than individuals separately reduces the costs of estimating allele frequencies at many loci in many populations. Theoretical and empirical studies show that sequencing pools comprising a limited number of individuals (typically fewer than 50) provides reliable allele frequency estimates, provided that the DNA pooling and DNA sequencing steps are carefully controlled. Unequal contributions of different individuals to the DNA pool and the mean and variance in sequencing depth both can affect the standard error of allele frequency estimates. To our knowledge, no study separately investigated the effect of these two factors on allele frequency estimates; so that there is currently no method to a priori estimate the relative importance of unequal individual DNA contributions independently of sequencing depth. We develop a new analytical model for allele frequency estimation that explicitly distinguishes these two effects. Our model shows that the DNA pooling variance in a pooled sequencing experiment depends solely on two factors: the number of individuals within the pool and the coefficient of variation of individual DNA contributions to the pool. We present a new method to experimentally estimate this coefficient of variation when planning a pooled sequencing design where samples are either pooled before or after DNA extraction. Using this analytical and experimental framework, we provide guidelines to optimize the design of pooled sequencing experiments. Finally, we sequence replicated pools of inbred lines of the plant Medicago truncatula and show that the predictions from our model generally hold true when estimating the frequency of known multilocus haplotypes using pooled sequencing.
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http://dx.doi.org/10.1111/1755-0998.12723 | DOI Listing |
J Infect Dis
December 2024
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Canada.
Background: CD4+ T cells expressing α4β7 are optimal targets for HIV infections, with higher pre-HIV α4β7hi expression linked to increased HIV acquisition and progression in South African women. However, similar associations were not observed in men who have sex with men (MSM) or people who inject drugs (PWID) in the Americas, indicating need for further research.
Methods: This retrospective case-control study enrolled heterosexual men and women from South Africa (HIV Vaccine Trials Network; HVTN 503) and East Africa (Partners Pre-Exposure Prophylaxis/Couples' Observational Study; PP/COS), quantifying α4β7 expression on CD4+ T cells as a predictor of subsequent HIV risk using flow cytometry analyses.
Med Decis Making
December 2024
Department of Health Policy, Stanford School of Medicine, Stanford, CA, USA.
Purpose: Individual-level state-transition microsimulations (iSTMs) have proliferated for economic evaluations in place of cohort state transition models (cSTMs). Probabilistic economic evaluations quantify decision uncertainty and value of information (VOI). Previous studies show that iSTMs provide unbiased estimates of expected incremental net monetary benefits (EINMB), but statistical properties of iSTM-produced estimates of decision uncertainty and VOI remain uncharacterized.
View Article and Find Full Text PDFLiver Int
January 2025
Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Introduction: Racial/ethnic disparities have been previously reported in renal and hepatic disease care; however, acute kidney injury (AKI) in the setting of cirrhosis (hepatorenal syndrome [HRS]-AKI) despite its complexity requiring a multidisciplinary approach, remains understudied.
Methods: To identify unique associations of clinical and sociodemographic factors with mortality and length of stay (LOS) among patients hospitalised with HRS-AKI, hierarchical regression analysis was conducted, along with a mediation analysis to estimate how race-related differences in in-hospital mortality were influenced by payer type, area household income, and clinical severity.
Results: Black patients demonstrated a significantly higher odds of in-hospital mortality, compared to their white counterparts, adjusting for (1) sex and age, (2) sex, age, payer type, and area household income and (3) sex, age, and clinical severity [OR 1.
Ochsner J
January 2024
The University of Queensland Medical School, Ochsner Clinical School, New Orleans, LA.
Despite the substantial expenditures on health care in the United States, persistent underperformance in health system metrics necessitates innovative approaches to address complex patient needs. The MedVantage Clinic in New Orleans, Louisiana, offers a regionally tailored, value-based primary care model targeting patients with high social and medical needs. This study provides an evaluation of the efficacy of the MedVantage Clinic in improving the cost of care and service utilization for this population.
View Article and Find Full Text PDFFront Public Health
December 2024
Department of Public Health, School of Public Health in Bytom Medical University of Silesia in Katowice, Piekarska, Poland.
In 2019, ozone was responsible for about 365,000 premature deaths worldwide (6.21 million healthy life years lost) and acute ozone exposure led to 16,800 premature deaths in the European Union. The aim of the study was to estimate the influence of NO, NO, wind direction (WD) wind speed (WS), air temperature (TA), and total radiation (GLR) on ozone concentration levels.
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