Biology subjects

Soares, M. A.

Publications and source records attributed to Soares, M. A..

9 recordsLinked to original sources

bioRxiv2026

DeepVir: A reproducible workflow for large-scale viral dark matter discovery

High-throughput sequencing (HTS) has revolutionized virosphere exploration. However, characterizing highly divergent viral sequences remains a bottleneck known as Viral Dark Matter (VDM). Numerous tools were developed to unravel such diversity, but they usually require complex prior HTS data analysis processes. Consequently, a common bottleneck to VDM exploration is the manual, chained execution of complex command-line applications. To address the need for automated and scalable viral discovery, we developed DeepVir, a reproducible Snakemake pipeline that integrates classical homology-based alignments with profile Hidden Markov Model (HMM) mining of the RNA-dependent RNA polymerase (RdRp). To validate the pipelines efficacy, we analyzed 385.23 GB of publicly available transcriptomic data (203 Sequence Read Archive libraries) from 49 American bat species. DeepVir successfully identified 179 distinct viral groups. This included 903 contigs spanning nine known viral families, enabling the characterization of novel genomes within Orthomyxoviridae (Influenza A H7N9), Picornaviridae, Alphaflexiviridae, Retroviridae (Spumaretrovirinae), Papillomaviridae, Herpesviridae, and Adenoviridae. Furthermore, the pipeline uncovered 170 putative novel VDM lineages. By employing deep homology searches and Sequence Similarity Network (SSN) visualization, we contextualized these highly divergent VDM sequences, revealing significant evolutionary relationships with the orders Mononegavirales and Bunyavirales. Notably, human-driven curation of the pipelines outputs allowed for the cross-library assembly of the first putative exogenous Spumavirus in the Americas. Ultimately, by automating complex bioinformatic processing steps, scalable pipelines like DeepVir empower researchers to prioritize the biological and epidemiological interpretation of their findings, accelerating the characterization of wildlife virospheres and enhancing pathogen genomic surveillance.

bioinformatics↗

bioRxiv2023

HIHISIV: a database of gene expression in HIV and SIV host immune response

In the battle of the host against lentiviral pathogenesis, the immune response is crucial. However, several questions remain unanswered about the interaction with different viruses and their influence on disease progression. The simian immunodeficiency virus (SIV) infecting nonhuman primates (NHP) is widely used as a model for the study of the human immunodeficiency virus (HIV). Both because they are evolutionarily linked and because they share physiological and anatomical similarities that are largely explored to understand the disease progression. The HIHISIV database was developed to support researchers to integrate and evaluate the large number of transcriptional data associated with the presence/absence of the pathogen (SIV or HIV) and the host response (NHP and human). The datasets are composed of microarray and RNA-Seq gene expression data that were selected, curated, analyzed, enriched, and stored in a relational database. Six query templates comprise the main data analysis functions and the resulting information can be downloaded. The HIHISIV database provides accurate resources for browsing and visualizing results and for more robust analyses of pre-existing data in transcriptome repositories. Database URLhttps://hihisiv.github.io

bioinformatics↗

bioRxiv2023

Fecal Virome of Coendou spinosus (Paraguaian Hairy Dwarf Porcupine)

The porcupine (Coendou spinosus) is a rodent species widely distributed in the Brazilian Atlantic forest. Like other rodent species, porcupines can be potential reservoirs of zoonotic agents. However, little is known about the viral diversity in these animals. Therefore, the objective of the present study was to evaluate, through massive sequencing, the virome of the feces of seven adult healthy free-living porcupines living in forest fragments from Silva Jardim, State of Rio de Janeiro, Brazil. A total of 41 viral families were classified, of which only seven were validated by both Kraken2 and Diamond taxonomic analysis tools, including bacteriophages (Siphoviridae, Myoviridae, Podoviridae), vertebrate viruses, such as Papillomaviridae, and unclassified RNA viruses. In addition, we also observed the presence of pathogenic bacteria and fungi already described in porcupines. The present study describes for the first time the microbiome in fecal samples from Brazilian porcupines, contributing to the global metagenomic characterization.

microbiology↗

bioRxiv2023

Fecal Virome of Southeastern Maned Sloth (Bradypus crinitus)

We report a viral metagenomic analysis of fecal samples from Bradypus crinitus, a recently described sloth species that occurs in the Atlantic Forest of Espirito Santo and Rio de Janeiro states, Southeast Brazil. Through Illumina sequencing, we generated a total of 2,065,344 raw reads, of which 945,386 reads (45.77%) passed the quality and size filter. The highest proportion of them was assigned to Eukarya, followed by Bacteria and only a small proportion to Virus. However, we identified 24 viral families using distinct taxonomic assignment tools, including phages and vertebrate viruses, such as retroviruses and papillomaviruses. Also, we identified four bacterial genus already associated with disease in sloths. Our study sheds light on the microbiome of a previously unexplored species, further contributing to the comprehension of metagenomic global diversity.

genetics↗

bioRxiv2023

Dmo2p is required for Cox2p stability and plays a role in mitochondrial redox balance.

Based on available platforms of Saccharomyces cerevisiae mitochondrial proteome and other high throughput studies, we identified the yeast gene DMO2 with a profile of genetic and physical interactions that indicate a putative role in mitochondrial respiration. Dmo2p is a homolog to human DMAC1 with two conserved cysteines in a Cx2C motif. Here, we localized Dmo2p in the mitochondrial inner membrane with the conserved cysteines facing the intermembrane space. The observed phenotypes of the dmo2 null mutant indicate a general function in cellular stress response; the mutant displayed poor growth on non-fermentative media at 37{degrees}C, and in oleate, it is more sensitive to heat and oxidative stress while its overexpression confers resistance to some of the tested stressors. Dmo2p topology and modeled structure suggested a functional redox role for the Cx2C motif sustained by site-directed mutagenesis of both cysteine residues. The respiratory deficiency of dmo2 mutants at 37{degrees}C led to a reduction in cytochrome c oxidase activity (COX) and the formation of bc1-COX supercomplexes; we also observed a rapid turnover of Cox2p, the subunit two of the cytochrome c oxidase complex that harbors the binuclear CuA center. Moreover, Dmo2p co-immunoprecipitated with Cox2p and components of CuA center maturation such as Sco1p and Sco2p; and finally, DMO2 overexpression can suppress cox23 respiratory deficiency, a mutant that has the mitochondrial copper homeostasis impaired. Overall, our data suggest that Dmo2p is required for Cox2p maturation, potentially by aiding proteins involved in copper transport and incorporation into Cox2p.

molecular biology↗

bioRxiv2022

Metagenomic analysis reveals novel dietary-related viruses in the gut virome of marmosets hybrids (Callithrix jacchus x Callithrix penicillata), Brazil

Viral metagenomics has contributed enormously to the characterization of a wide range of viruses infecting animals of all phyla in the last decades. Among Neotropical primates, especially those free-living introduced, knowledge about viral diversity remains poorly studied. Therefore, through the use of metagenomics based on virus enrichment, we explored the viral microbiota present in the feces of introduced common marmosets (Callithrix sp.) in three locations from the Silva Jardim region in the State of Rio de Janeiro, Brazil. Fecal samples were collected from nine marmosets, pooled into three sample pools and sequenced on Illumina MiSeq platform. Sequence reads were analyzed using a viral metagenomic analysis pipeline and two novel insect viruses belonging to the Parvoviridae and Baculoviridae families were identified. The complete genome of a densovirus (Parvoviridae family) of 5,309 nucleotides (nt) was obtained. The NS1 and VP1 proteins share lower than 32% sequence identity with the corresponding proteins of known members of the subfamily Densovirinae. Phylogenetic analysis suggests that this virus represents a new genus, named Tritonambidensovirus due to telomeric structures at the 3 and 5 ends of the genome. The novel species received the name Fecalis tritonambidensovirus 1. The complete circular genome of a baculovirus of 107,191 nt was also obtained, showing 60.8% sequence identity with the most closely related member of the Baculoviridae family. Phylogenetic analysis suggests that this virus represents a new species of Betabaculovirus, named Callithrix fecalis granulovirus. In addition, sequences from several families of arthropods in the three pools evaluated were characterized (contigs ranging from 244 to 6,750 nt), corroborating the presence of possible insect hosts with which these new viruses may be associated. Our study expands the knowledge about two viral families known to infect insects, an important component of the marmosets diet. This identification in hosts feces samples demonstrates one of the many uses of this type of data and could serve as a basis for future research characterizing viruses in wildlife using noninvasive samples.

genomics↗

bioRxiv2022

Discovery of two novel Torque Teno viruses in Callithrix penicillata provides insights on Anelloviridae diversification dynamics

1.The development of high throughput sequencing (HTS) technologies and metagenomics protocols deeply impacted the discovery of viral diversity. Moreover, the comprehension of evolution and immunology of the Neotropical primates (NP) and their susceptibility to infectious diseases are central for the characterization of the scope of etiological agents that may impact global health, due to their evolutionary proximity to Old World primates, including humans. In the present work, novel anelloviruses were detected and characterized through HTS protocols in the NP Callithrix penicillata, the common black-tufted marmoset. De novo assembly of generated sequences was carried out and a total of 15 contigs were identified with complete Anelloviridae ORF1 gene, two of them including a flanking GC-rich region, confirming the presence of two whole novel genomes of ~3kb. The identified viruses were monophyletic within the Epsilontorquevirus genus, a lineage harboring previously reported anelloviruses infecting hosts from the Cebidae family. The genetic divergence found in the new viruses characterized two novel species, named Epsilontorquevirus callithrichensis I and II. The phylogenetic pattern inferred for the Epsilontorquevirus genus was consistent with the topology of their host species tree, echoing a virus-host diversification model observed in other viral groups. This study expands the host span of Anelloviridae and provides insights into their diversification dynamics, highlighting the importance of sampling animal viral genomes to obtain a clearer depiction of their long-term evolutionary processes.

genetics↗

bioRxiv2020

SARS-CoV-2 genomic and quasispecies analyses in cancer patients reveal relaxed intrahost virus evolution

Numerous factors have been identified to influence susceptibility to SARS-CoV-2 infection and disease severity. Cancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. We have determined the full-length SARS-CoV-2 genomic sequences of cancer patients and healthcare workers (HCW; non-cancer controls) by deep sequencing and investigated the within-host viral quasispecies of each infection, quantifying intrahost genetic diversity. Naso- and oropharyngeal SARS-CoV-2+ swabs from 57 cancer patients and 14 healthcare workers (HCW) from the Brazilian Cancer Institute were collected in April-May 2020. Complete genome amplification using ARTIC network V3 multiplex primers was performed followed by next-generation sequencing. Assemblies were conducted in Geneious R11, where consensus sequences were extracted and intrahost single nucleotide variants (iSNVs) were identified. Maximum likelihood phylogenetic analysis was performed using PhyMLv.3.0 and lineages were classified using Pangolin and CoV-GLUE. Phylogenetic analysis showed that all but one strain belonged to clade B1.1. Four genetically linked mutations known as the globally dominant SARS-CoV-2 haplotype (C241T, C3037T, C14408T and A23403G) were found in the majority of consensus sequences. SNV signatures of previously characterized Brazilian genomes were also observed in most samples. Another 85 SNVs were found at a lower frequency (1.4-19.7%). Cancer patients displayed a significantly higher intrahost viral genetic diversity compared to HCW (p = 0.009). Intrahost genetic diversity in cancer patients was independent of SARS-CoV-2 Ct values, and was not associated with disease severity, use of corticosteroids, or use of antivirals, characteristics that could influence viral diversity. Such a feature may explain, at least in part, the more adverse outcomes to which cancer/COVID-19 patients experience. Author SummaryCancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. In this study, phylogenetic and variation analysis of SARS-CoV-2 genomes from cancer patients and non-cancer healthcare workers at the Brazilian National Cancer Institute were characterized by deep sequencing. Viral genomes showed signatures characteristic of Brazilian viruses, consistent with the hypothesis of local, community transmission rather than virus importation from abroad. Despite most genomes in patients and healthcare workers belonging to the same lineage, intrahost variability was higher in cancer patients when compared to non-cancer counterparts. The intrahost genomic diversity analysis presented in our study highlights the relaxed evolution of SARS-CoV-2 in a vulnerable population of cancer patients. The high number of minor variations can result in the selection of immune escape variants, resistance to potential drugs, and/or increased pathogenicity. The impact of this higher intrahost variability over time warrants further investigation.

microbiology↗

bioRxiv2017

Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer

The human papillomavirus (HPV) is present in a significant fraction of head-and-neck squamous cell cancer (HNSCC). However, a comprehensive understanding of disease progression profiles comparing HPV+ and HPV- HNSCC cases is still lacking. The main goal of this study was to identify distinct co-expression patterns between HPV+ and HPV- HNSCC and to provide insights into potential regulatory mechanisms/effects (such as methylation and mutation) within the analyzed networks. For conducting this, we selected 276 samples from The Cancer Genome Atlas database comprising data of gene expression, methylation profiles and mutational patterns, in addition to clinical information (HPV status and tumor staging). We further added external information such as the identification of transcription factors to the networks. Genes were selected as differentially expressed and differentially methylated based on HPV status, of which 12 genes were doubly selected, including SYCP2, GJB6, FLRT3, PITX2 and CCNA1. Weight correlation network analysis was used to identify co-expression modules and a systematic approach was applied to refine them and identify key regulatory elements integrating results from the other omics. Three main modules were associated with distinct co-expression patterns in HPV+ versus HPV- HNSCC. The molecular signatures found were mainly related to cell fate specification, keratinocyte differentiation, focal adhesion and regulation of protein oligomerization. This study provides comprehensive insights into complex genetic and epigenetic particularities in the development and progression of HNSCC in patients according to HPV status, identifying unseen gene interactions, and may contribute to unveiling specific genes/pathways as novel therapeutic targets for HNSCC.

systems biology↗