Biology subjects

Ferreira, R. C.

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

6 recordsLinked to original sources

bioRxiv2025

Oncogenic HPV types identified in Paleolithic and Chalcolithic human genome sequencing data from Ust'-Ishim and Ötzi

Human papillomaviruses (HPVs) are ancient viruses with diverse lineages infecting epithelial tissues in primates and humans. Although contemporary distribution and clinical importance are well understood, there is limited knowledge about their occurrence among prehistoric human populations. We investigated the presence of HPV in ancient anatomically modern humans (AMHs) by analyzing genome sequencing data from two exceptionally preserved individuals: Ust-Ishim ([~]45,000 years BP) and Otzi the Iceman ([~]5,300 years BP). Using a combination of reference-guided mapping and ancient DNA authentication criteria, we searched for HPV sequences in these ancient genomes. We detected high-confidence papillomavirus fragments in both individuals. Further phylogenetic and comparative analyses revealed that the reconstructed sequences belong to HPV16, the most oncogenic HPV lineage. Our study presents the earliest molecular evidence of HPV16 in anatomically modern humans (AMHs), pushing back its evolutionary history and challenging the idea that HPV16A entered Homo sapiens through Neanderthal interbreeding. Our results suggest that HPV16 was already present in modern humans during the Upper Paleolithic, indicating a long-standing host-virus association independent of Neanderthal transmission.

evolutionary biology↗

bioRxiv2023

Reconstructing prehistoric viral genomes from Neanderthal sequencing data

DNA viruses that produce persistent infections have been proposed as potential causes for the extinction of Neanderthals and therefore, the identification of viral genome remnants in Neanderthal sequence reads is an initial step to address this hypothesis. Here, as proof of concept, we searched for viral remnants in sequence reads of Neanderthal genome data by mapping to adenovirus, herpesvirus and papillomavirus, which are double stranded DNA viruses that may establish lifelong latency and can, produce persistent infections. The reconstructed ancient viral genomes of adenovirus, herpesvirus and papillomavirus revealed conserved segments, with nucleotide identity to extant viral genomes, and variable regions in coding regions with substantial divergence to extant close relatives. Sequence reads mapped to extant viral genomes showed deamination patterns of ancient DNA and that these ancient viral genomes showed divergence consistent with the age of these samples ({approx}50,000 years) and viral evolutionary rates (10-5 to 10-8 substitutions/site/year). Analysis of random effects shows that the Neanderthal mapping to genomes of extant persistent viruses is above the expected by random similarities of short reads. Also, negative control with a nonpersistent DNA virus does not yield statistically significant assemblies. This work demonstrates the feasibility of identifying viral genome remnants in archaeological samples with signal-to-noise assessment.

genomics↗

bioRxiv2019

Simultaneous mRNA and protein quantification at the single-cell level delineates trajectories of CD4+ T-cell differentiation

The transcriptomic and proteomic characterisation of CD4+ T cells at the single-cell level has been performed traditionally by two largely exclusive types of technologies: single cell RNA-sequencing (scRNA-seq) technologies and antibody-based cytometry. Here we demonstrate that the simultaneous targeted quantification of mRNA and protein expression in single-cells provides a high-resolution map of human primary CD4+ T cells, and identified precise trajectories of Th1, Th17 and regulatory T-cell (Treg) differentiation in blood and tissue. Furthermore, the sensitivity provided by this massively-parallel multi-omics approach revealed novel insight into the mechanism of expression of CD80 and CD86 on the surface of activated CD4+ Tregs and demonstrate their potential to identify recently activated T cells in circulation. This transcriptomic and proteomic hybrid technology provides a cost-effective solution to dissect the heterogeneity of immune cell populations, including more precise and detailed descriptions of the differentiation and activation of circulating and tissue-resident cells in response to therapies and in stratification of patients.

immunology↗

bioRxiv2017

Differential distribution of Neandertal genomic signatures in human mitochondrial haplogroups

Genetic contributions of Neanderthals to the modern human genome have been evidenced by comparison of present-day human genomes with paleogenomes suggesting that the Neanderthal introgression is higher in Asians and Europeans and lower in Africans. Neanderthal signatures in extant human genomes are attributed to intercrosses between Neanderthals and archaic Anatomically Modern Humans (AMH). Although Neanderthal signatures are well documented in the nuclear genome, it has been proposed that there is no contribution of Neanderthal mitochondrial DNA to contemporary human genomes. Here we show that modern human mitochondrial genomes contain potential 66 Neanderthal signatures, or Neanderthal single nucleotide variants (N-SNVs) being 36 in coding regions of which 7 are nonsynonymous. Also, 7 N-SNVs are associated with traits such as cycling vomiting syndrome, Alzheimers disease, Parkinsons disease and 2 N-SNVs are associated with intelligence quotient. Based on recombination tests, Principal Component Analysis (PCA) and the complete absence of these N-SNVs in 41 archaic AMH mitogenomes we conclude that convergent evolution due to homoplasy and not recombination, explains the presence of N-SNVs in present-day human mitogenomes.

genomics↗

bioRxiv2017

Cells With Treg-Specific FOXP3 Demethylation But Low CD25 Are Prevalent In Autoimmunity

Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3+ cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3+ cells within CD127lowCD25low CD4+ T cells (here defined as CD25lowFOXP3+ T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes. We show that CD25lowFOXP3+ T cells share phenotypic features resembling conventional CD127lowCD25highFOXP3+ Tregs, including demethylation of the Treg-specific epigenetic control region in FOXP3 that is highly enriched in HELIOS+ cells, and lack of IL-2 production. As compared to conventional Tregs, more CD25lowFOXP3+HELIOS+ T cells are in cell cycle (33.0% vs 20.7% Ki-67+; P = 1.3 x 10-9) and express the late-stage inhibitory receptor PD-1 (67.2% vs 35.5%; P = 4.0 x 10-18), while having reduced expression of the early-stage inhibitory receptor CTLA-4, as well as other Treg markers, such as FOXP3 and CD15s. The number of CD25lowFOXP3+ T cells are highly correlated (P = 1.2 x 10-19) with the proportion of CD25highFOXP3+ T cells in cell cycle (Ki-67+). These findings suggest that CD25lowFOXP3+ T cells represent a subset of Tregs that are derived from CD25highFOXP3+ T cells, and are a peripheral marker of recent Treg expansion in response to an autoimmune reaction in tissues.\n\nHighlights- FOXP3+ compartment within CD127lowCD25low T cells is expanded in autoimmune patients.\n\n- Increased numbers of CD25lowFOXP3+ T cells are a circulating marker of autoimmunity.\n\n- CD25lowFOXP3+ HELIOS+ T cells are fully demethylated at the FOXP3 TSDR.\n\n- CD25lowFOXP3+ T cells could represent a terminal stage of regulatory T cells.

immunology↗

bioRxiv2017

Chromosome contacts in activated T cells identify autoimmune disease-candidate genes

BackgroundAutoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4+ T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes.\n\nResultsWithin four hours, activation of CD4+ T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C. By integrating promoter capture Hi-C data with genetic associations for five autoimmune diseases we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153 kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach.\n\nConclusionsOur systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes.

genomics↗