Augur: a bioinformatics toolkit for phylogenetic analyses of human pathogens

The analysis of human pathogens requires a diverse collection of bioinformatics tools. These tools include standard genomic and phylogenetic software and custom software developed to handle the relatively numerous and short genomes of viruses and bacteria. Researchers increasingly depend on the outputs of these tools to infer transmission dynamics of human diseases and make actionable recommendations to public health officials (Black et al., 2020; Gardy et al., 2015). In order to enable real-time analyses of pathogen evolution, bioinformatics tools must scale rapidly with the number of samples and be flexible enough to adapt to a variety of questions and organisms. To meet these needs, we developed Augur, a bioinformatics toolkit designed for phylogenetic analyses of human pathogens

Deep generative models for T cell receptor protein sequences.

Probabilistic models of adaptive immune repertoire sequence distributions can be used to infer the expansion of immune cells in response to stimulus, differentiate genetic from environmental factors that determine repertoire sharing, and evaluate the suitability of various target immune sequences for stimulation via vaccination. Classically, these models are defined in terms of a probabilistic V(D)J recombination model which is sometimes combined with a selection model. In this paper we take a different approach, fitting variational autoencoder (VAE) models parameterized by deep neural networks to T cell receptor (TCR) repertoires. We show that simple VAE models can perform accurate cohort frequency estimation, learn the rules of VDJ recombination, and generalize well to unseen sequences. Further, we demonstrate that VAE-like models can distinguish between real sequences and sequences generated according to a recombination-selection model, and that many characteristics of VAE-generated sequences are similar to those of real sequences

Deep generative models for T cell receptor protein sequences.

Probabilistic models of adaptive immune repertoire sequence distributions can be used to infer the expansion of immune cells in response to stimulus, differentiate genetic from environmental factors that determine repertoire sharing, and evaluate the suitability of various target immune sequences for stimulation via vaccination. Classically, these models are defined in terms of a probabilistic V(D)J recombination model which is sometimes combined with a selection model. In this paper we take a different approach, fitting variational autoencoder (VAE) models parameterized by deep neural networks to T cell receptor (TCR) repertoires. We show that simple VAE models can perform accurate cohort frequency estimation, learn the rules of VDJ recombination, and generalize well to unseen sequences. Further, we demonstrate that VAE-like models can distinguish between real sequences and sequences generated according to a recombination-selection model, and that many characteristics of VAE-generated sequences are similar to those of real sequences

Dynamics of HIV DNA reservoir seeding in a cohort of superinfected Kenyan women.

A reservoir of HIV-infected cells that persists despite suppressive antiretroviral therapy (ART) is the source of viral rebound upon ART cessation and the major barrier to a cure. Understanding reservoir seeding dynamics will help identify the best timing for HIV cure strategies. Here we characterize reservoir seeding using longitudinal samples from before and after ART initiation in individuals who sequentially became infected with genetically distinct HIV variants (superinfected). We previously identified cases of superinfection in a cohort of Kenyan women, and the dates of both initial infection and superinfection were determined. Six women, superinfected 0.2-5.2 years after initial infection, were subsequently treated with ART 5.4-18.0 years after initial infection. We performed next-generation sequencing of HIV gag and env RNA from plasma collected during acute infection as well as every ~2 years thereafter until ART initiation, and of HIV DNA from PBMCs collected 0.9-4.8 years after viral suppression on ART. We assessed phylogenetic relationships between HIV DNA reservoir sequences and longitudinal plasma RNA sequences prior to ART, to determine proportions of initial and superinfecting variants in the reservoir. The proportions of initial and superinfection lineage variants present in the HIV DNA reservoir were most similar to the proportions present in HIV RNA immediately prior to ART initiation. Phylogenetic analysis confirmed that the majority of HIV DNA reservoir sequences had the smallest pairwise distance to RNA sequences from timepoints closest to ART initiation. Our data suggest that while reservoir cells are created throughout pre-ART infection, the majority of HIV-infected cells that persist during ART entered the reservoir near the time of ART initiation. We estimate the half-life of pre-ART DNA reservoir sequences to be ~25 months, which is shorter than estimated reservoir decay rates during suppressive ART, implying continual decay and reseeding of the reservoir up to the point of ART initiation

emmahodcroft/ncov_2021

This is the version of ncov_2021 used to generate the main Alpha & Delta phylogenies to detect introductions to Switzerland (without the modifications to reduce the background sampling). With the background sampling, the same code was used to produce the 10 re-runs

emmahodcroft/ncov_2021: Release for Geneva Manuscript

This is the version of ncov_2021 used to generate the main Alpha and Delta+Omicron phylogenies to investigate outbreaks in Geneva that were sampled focusing around schools

Parâmetros bioquímicos de equinos submetidos à simulação de prova de enduro recebendo dietas com adição de óleo de soja Biochemical parameters of horses submitted to an endurance simulation receiving diets with soybean oil addition

Com o objetivo de verificar o efeito da adição de níveis crescentes de óleo no concentrado sobre a atividade plasmática das enzimas creatina quinase (CK), aspartato aminotransferase (AST) e lactato desidrogenase (LDH) como indicativo de metabolismo energético, foram fornecidas dietas experimentais compostas de cinco níveis de óleo (controle, 6, 12, 18 e 24% do concentrado). Utilizaram-se 20 equinos da raça Árabe, peso médio de 400 kg, submetidos a prova de enduro de 80 km em esteira rolante. O enduro foi dividido em quatro anéis de 20 km, com duração média de 1 hora e dez minutos. A adição de óleo e a distância percorrida tiveram efeitos sobre as variáveis AST, CK e LDH, que apresentaram as respectivas expressões: AST (7,045-0,2292x+0,007991x2+0,008517z- 0,0003282xz), CK (8,06-,07020x+0,05546x2-0,001262x3+0,01204z+0,0006207xz) e LDH (6,624-0,3522x+0,03448x2-0,0008382x3+0,02401z-0,0007489xz) . O óleo é uma importante e bem aproveitada fonte de energia para equinos em exercício, pois sua adição na dieta de animais submetidos a prova de enduro promoveu alteração metabólica que favorece a produção de energia. O metabolismo animal poupou suas reservas energéticas oriundas da glicose, favorecendo a utilização do óleo. A menor atividade plasmática das enzimas AST, CK e LDH com a adição de óleo nas dietas indica direcionamento do metabolismo energético para a &#946;-oxidação. Como apresentam várias isoenzimas, as enzimas estudadas atuam amplamente no metabolismo energético, favorecendo a constante reposição de ATP ao longo do exercício.<br>The objective of this study was to verify the effect of increasing soybean oil addition levels in the concentrate, on the enzymatic activity CK (Creatine Kinase), LDH (Lactate Dehydrogenase), AST (Astarte aminostrafase), as an indication of energetic metabolism. Compond experimental diets were given with five oil levels (control, 6, 12, 18 and 24% concentrate). Twenty Arabian equines, average weight 400 kg were submitted to a 80 km endurance race on a treadmill. The endurance was divided into four 20 km rings with an average duration of one hour and 10 minutes. A significant effect of oil addition and the covered distance was observed on the variables AST, CK, LDH and they present the respective expressions AST and (7,045-0,2292x+0,007991x2+ 0,008517z- 0,0003282xz) CKand(8,06-,07020x+0,05546x2-0,001262x3+0,01204z+0,0006207xz) , LDH and (6,624-0,3522x+0,03448x2-0,0008382x3+0,02401z-0,0007489xz) . The oil is an important and well-used energy source for horses in exercise, because its addition to the diet of animals submitted to endurance test cause metabolic alteration that favored energy production. The animal metabolism save its energy reserves derived from glucose and favored the use of the oil. The smaller plasmatic activity of the AST, CK and LDH, enzymes with the addition of oil to the diets indicated directioning of the energy metabolism to &#946;-oxidation. As the enzymes show several isoenzymes, it was concluded that the enzymes studied act widely on the energetic metabolism, favoring constant ATP reposition during all exercise