Study design and the sampling of deleterious rare variants in biobank-scale datasets.

One key component of study design in population genetics is the "geographic breadth" of a sample (i.e., how broad a region across which individuals are sampled).

TRIO RVEMVS: A Bayesian framework for rare variant association analysis with expectation-maximization variable selection using family trio data.

It is commonly reported that rare variants may be more functionally related to complex diseases than common variants. However, individual rare variant association tests remain challenging due to low minor allele frequency in the available samples. This paper proposes an expectation maximization variable selection (EMVS) method to simultaneously detect common and rare variants at the individual variant level using family trio data.

The design of mapping populations: Impacts of geographic scale on genetic architecture and mapping efficacy for defense and immunity.

Genome-wide association studies (GWAS) have yielded tremendous insight into the genetic architecture of trait variation. However, the collections of loci they uncover are far from exhaustive. As many of the complicating factors that confound or limit the efficacy of GWAS are exaggerated over broad geographic scales, a shift toward more analyses using mapping panels sampled from narrow geographic localities ("local" populations) could provide novel, complementary insights.

Long-acting growth hormone in 2022.

After the isolation of pituitary growth hormone (GH) in 1957, this form of GH, always in limited supply, was the only drug available for the treatment of GH deficiency. In 1985, recombinant GH became available, and the modalities of GH therapies changed dramatically as the supply was unlimited. New indications for GH in pediatrics and adult medicine were developed.

Population genetic models for the spatial spread of adaptive variants: A review in light of SARS-CoV-2 evolution.

Theoretical population genetics has long studied the arrival and geographic spread of adaptive variants through the analysis of mathematical models of dispersal and natural selection. These models take on a renewed interest in the context of the COVID-19 pandemic, especially given the consequences that novel adaptive variants have had on the course of the pandemic as they have spread through global populations. Here, we review theoretical models for the spatial spread of adaptive variants and identify areas to be improved in future work, toward a better understanding of variants of concern in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) evolution and other contemporary applications.

Turner Syndrome: An Update.

Turner syndrome is the most common sex chromosome abnormality in women. Infertility and short stature are the most striking findings seen in these patients. Unfortunately, many girls are still being diagnosed too late and therefore early diagnosis and treatment key.

A comprehensive electronic health record-enabled smoking treatment program: Evaluating reach and effectiveness in primary care in a multiple baseline design.

Effective treatments for smoking cessation exist but are underused. Proactive chronic care approaches may enhance the reach of cessation treatment and reduce the prevalence of smoking in healthcare systems. This pragmatic study evaluated a population-based Comprehensive Tobacco Intervention Program (CTIP) implemented in all (6) adult primary care clinics in a Madison, Wisconsin, USA healthcare cooperative, assessing treatment reach, reach equity, and effectiveness in promoting smoking cessation.

Locus-Specific Characterization of Human Endogenous Retrovirus Expression in Prostate, Breast, and Colon Cancers.

Human endogenous retroviruses (HERV) have been implicated in a variety of diseases including cancers. Recent research implicates HERVs in epigenetic gene regulation. Here we utilize a recently developed bioinformatics tool for identifying HERV expression at the locus-specific level to identify differential expression of HERVs in matched tumor-normal RNA-sequencing (RNA-seq) data from The Cancer Genome Atlas.

HAPHPIPE: Haplotype Reconstruction and Phylodynamics for Deep Sequencing of Intrahost Viral Populations.

Deep sequencing of viral populations using next-generation sequencing (NGS) offers opportunities to understand and investigate evolution, transmission dynamics, and population genetics. Currently, the standard practice for processing NGS data to study viral populations is to summarize all the observed sequences from a sample as a single consensus sequence, thus discarding valuable information about the intrahost viral molecular epidemiology. Furthermore, existing analytical pipelines may only analyze genomic regions involved in drug resistance, thus are not suited for full viral genome analysis.

Validation of Variant Assembly Using HAPHPIPE with Next-Generation Sequence Data from Viruses.

Next-generation sequencing (NGS) offers a powerful opportunity to identify low-abundance, intra-host viral sequence variants, yet the focus of many bioinformatic tools on consensus sequence construction has precluded a thorough analysis of intra-host diversity. To take full advantage of the resolution of NGS data, we developed HAplotype PHylodynamics PIPEline (HAPHPIPE), an open-source tool for the de novo and reference-based assembly of viral NGS data, with both consensus sequence assembly and a focus on the quantification of intra-host variation through haplotype reconstruction. We validate and compare the consensus sequence assembly methods of HAPHPIPE to those of two alternative software packages, HyDRA and Geneious, using simulated HIV and empirical HIV, HCV, and SARS-CoV-2 datasets.

Drug Resistance Prediction Using Deep Learning Techniques on HIV-1 Sequence Data.

The fast replication rate and lack of repair mechanisms of human immunodeficiency virus (HIV) contribute to its high mutation frequency, with some mutations resulting in the evolution of resistance to antiretroviral therapies (ART). As such, studying HIV drug resistance allows for real-time evaluation of evolutionary mechanisms. Characterizing the biological process of drug resistance is also critically important for sustained effectiveness of ART.

Corrigendum: A 28-Year History of HIV-1 Drug Resistance and Transmission in Washington, DC.

[This corrects the article DOI: 10.3389/fmicb.2019.

A 28-Year History of HIV-1 Drug Resistance and Transmission in Washington, DC.

Washington, DC consistently has one of the highest annual rates of new HIV-1 diagnoses in the United States over the last 10 years. To guide intervention and prevention strategies to combat DC HIV infection, it is helpful to understand HIV transmission dynamics in a historical context. Toward this aim, we conducted a retrospective study (years 1987-2015) of 3,349 HIV sequences (1,026 bp) from 1,996 individuals living in the DC area belonging to three different cohorts.