Biology subjects

Ferreira, R.-C.

Publications and source records attributed to Ferreira, R.-C..

3 recordsLinked to original sources

bioRxiv2023

Within-host rates of insertion and deletion in the HIV-1 surface envelope glycoprotein

Under selection by neutralizing antibodies, the HIV-1 envelope glycoprotein gp120 undergoes rapid evolution within hosts, particularly in regions encoding the five variable loops (V1-V5). Indel polymorphisms are abundant in these loops, where they can facilitate immune escape by modifying the length, composition and glycosylation profile of these structures. Here, we present a comparative analysis of within-host indel rates and characteristics within the variable regions of gp120. We analyzed a total of 3,437 HIV-1 gp120 sequences sampled longitudinally from 29 different individuals using coalescent models in BEAST. Next, we used Historian to reconstruct ancestral sequences from the resulting tree samples, and fit a Poisson generalized linear model to the distribution of indel events to estimate their rates in the five variable loops. Overall, the mean insertion and deletion rates were 1.6 x 10-3 and 2.5 x 10-3/ nt / year, respectively, with significant variation among loops. Insertions and deletions also followed similar length distributions, except for significantly longer indels in V1 and V4 and shorter indels in V5. Insertions in V1, V2, and V4 tended to create new N-linked glycosylation sites significantly more often than expected by chance, which is consistent with positive selection to alter glycosylation patterns.

evolutionary biology↗

bioRxiv2022

bayroot: Bayesian sampling of HIV-1 integration dates by root-to-tip regression

The composition of the latent HIV-1 reservoir is shaped by when proviruses integrated into host genomes. These integration dates can be estimated by phylogenetic methods like root-to-top (RTT) regression. However, RTT does not accommodate variation in the number of substitutions over time, uncertainty in estimating the molecular clock or the position of the root in the tree. To address these limitations, we implemented a Bayesian extension of RTT as an R package (bayroot), which enables the user to incorporate prior information about the time of infection and start of antiretroviral therapy. Taking an unrooted maximum likelihood tree as input, we use a Metropolis-Hastings algorithm to sample three parameters (the molecular clock, the location of the root, and the time associated with the root) from the posterior distribution. Next, we apply rejection sampling to this posterior sample of model parameters to simulate integration dates for HIV proviral sequences. To validate this method, we use the R package treeswithintrees to simulate time-scaled trees relating samples of actively- and latently-infected T cells from a single host. We find that bayroot yields significantly more accurate estimates of integration dates than conventional RTT under a range of model settings.

bioinformatics↗

bioRxiv2021

CoVizu: Rapid analysis and visualization of the global diversity of SARS-CoV-2 genomes

Phylogenetics has played a pivotal role in the genomic epidemiology of SARS-CoV-2, such as tracking the emergence and global spread of variants, and scientific communication. However, the rapid accumulation of genomic data from around the world -- with over two million genomes currently available in the GISAID database -- is testing the limits of standard phylogenetic methods. Here, we describe a new approach to rapidly analyze and visualize large numbers of SARS-CoV-2 genomes. Using Python, genomes are filtered for problematic sites, incomplete coverage, and excessive divergence from a strict molecular clock. All differences from the reference genome, including indels, are extracted using minimap2, and compactly stored as a set of features for each genome. For each Pango lineage (https://cov-lineages.org), we collapse genomes with identical features into variants, generate 100 bootstrap samples of the feature set union to generate weights, and compute the symmetric differences between the weighted feature sets for every pair of variants. The resulting distance matrices are used to generate neigihbor-joining trees in RapidNJ and converted into a majority-rule consensus tree for the lineage. Branches with support values below 50% or mean lengths below 0.5 differences are collapsed, and tip labels on affected branches are mapped to internal nodes as directly-sampled ancestral variants. Currently, we process about million genomes in approximately nine hours on 34 cores. The resulting trees are visualized using the JavaScript framework D3.js as beadplots, in which variants are represented by horizontal line segments, annotated with beads representing samples by collection date. Variants are linked by vertical edges to represent branches in the consensus tree. These visualizations are published at https://filogeneti.ca/CoVizu. All source code was released under an MIT license at https://github.com/PoonLab/covizu.

bioinformatics↗