Search bioRxiv⌕ Search

Biology subjects

Oliveira, T. d.

Publications and source records attributed to Oliveira, T. d..

3 recordsLinked to original sources
bioRxiv2023

SeqPanther: Sequence manipulation and mutation statistics toolset

Pathogen genomes harbor critical information necessary to support genomic investigations that inform public health interventions such as treatment, control, and eradication. To extract this information, their sequences are analysed to identify structural variations such as single nucleotide polymorphisms (SNPs) and insertions and deletions (indels) that may be associated with phenotypes of interest. Typically, this involves generating a consensus sequence from raw reads, aligning it to a reference and identifying positions where variations occur. Several pipelines exist to map raw reads and assemble whole genomes for downstream analysis. However, there is no easy to use, freely available bioinformatics quality control (QC) tool to explore mappings for both positional codons and nucleotide distributions in mapped short reads of microbial genomes. To address this problem, we have developed a fast and accurate tool to summarise read counts associated with codons, nucleotides, and indels in mapped next-generation sequencing (NGS) short reads. The tool, developed in Python, also provides a visualization of the genome sequencing depth and coverage. Furthermore, the tool can be run in single or batch mode, where several genomes need to be analysed. Our tool produces a text-based report that enables quick review or can be imported into any analytical tool for upstream analysis. Additionally, the tool also provides functionality to modify the consensus sequences by adding, masking, or restoring to wild type mutations specified by the user. AvailabilitySeqPanther is available at https://github.com/codemeleon/seqPanther, along with the necessary documentation for installation and usage.

bioinformatics↗
bioRxiv2021

HIV-specific CD8+ T-cells in tonsils express exhaustive TRM-like signatures

Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue resident memory ( TRM) CD8+ T-cells is of great interest, but limited data exist on TRMs within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and transcriptionally TRM-like profile that is distinct from blood. In PLWH, CD8+ TRM-like cells are highly expanded and adopt a more cytolytic, activated and exhausted phenotype characterized by increased expression of CD69, PD-1 and perforin, but reduced CD127. This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood. Single-cell profiling of these cells revealed a clear transcriptional signature of T-cell activation, clonal expansion and exhaustion ex-vivo. In contrast, this signature was absent from HIV-specific CD8+ T-cells in tonsils isolated from a natural HIV controller, who expressed lower levels of cell surface PD-1 and CXCR5, and reduced transcriptional evidence of T-cell activation, exhaustion and cytolytic activity. Thus, we show that HIV-specific TRM-like CD8+ T-cells in tonsils from non-HIV controllers are enriched for activation and exhaustion profiles compared to those in blood, suggesting that lymphoid HIV-specific CD8+ TRM cells are potentially ideal candidates for immunotherapy to modulate their ability to targeting the HIV reservoirs.

immunology↗