Biology subjects

Sabino, E. C.

Publications and source records attributed to Sabino, E. C..

10 recordsLinked to original sources

bioRxiv2026

From mice to humans: A multi-omic predictive framework for translational immunology

Mice are key preclinical animal models in vaccine and immunological research, yet their predictive value for human immunity remains contested. Here, we evaluated the translatability of murine models across inactivated and subunit vaccination (influenza, hepatitis B), acute infection (S. aureus, E. coli), and injury (burns and trauma), integrating transcriptomic profiles with sequence evolution, cis-regulatory architecture, and functional annotation. Functional modules were more conserved between species than individual orthologous genes. Translational accuracy depended on stimulus intensity, as infections and injuries engaged conserved signatures, while single-dose vaccination diverged. We then built multilayer models to predict human expression rank and direction of change, and to classify shared leading-edge genes. Adding evolutionary and regulatory layers improved these predictions. We provide a step-by-step R Markdown notebook to apply the models to user data. The study code and datasets are available at https://github.com/wapsyed/mousetohuman_multilayer

bioinformatics↗

bioRxiv2026

Genomic Epidemiology of Canine Distemper Virus (CDV) in Neotropical Primates in Brazil Reveals Multiple Spillover Events and Convergent Evolution at Hemagglutinin Residue 519

Canine distemper virus (CDV; Morbillivirus canis) is a multi-host paramyxovirus primarily maintained in the order Carnivora. However, recent outbreaks in Neotropical primates suggest recurrent cross-species spillover into non-human primates. Between May and July 2022, seven marmosets (Callithrix penicillata) were found dead in urban and peri-urban areas of Montes Claros, Minas Gerais, Brazil. Viral metagenomic sequencing recovered two near complete CDV genomes directly from liver samples. Maximum likelihood and Bayesian phylogenetic analyses placed these genomes within the South American CDV lineage and supported at least three independent zoonotic introductions into Callithrix populations. Domestic dogs (Canis lupus familiaris) were inferred as the most likely source and the crab-eating fox (Cerdocyon thous) as a probable bridge host. Ancestral-state reconstruction identified a substitution at position 519 of the hemagglutinin (H) protein (R519I in the two primate clades and R519G in a singleton primate sequence). In silico modelling of the marmoset signaling lymphocytic activation molecule (SLAM) complex was consistent with a modest reorganisation of the receptor-binding head in the 519-substituted variants (ipTM = 0.82), generating a testable hypothesis that this residue may contribute to adaptation at the primate SLAM receptor interface and is associated with altered predicted docking orientation for the receptor. Together, these findings suggest that residue 519 is a candidate marker of CDV adaptation to Neotropical primates and emphasise the importance of integrating genomic surveillance with domestic dog vaccination efforts under a One Health framework to reduce the threat of CDV spillover to vulnerable wildlife populations.

genomics↗

bioRxiv2026

FDXR Upregulation by p63/p73 is a Prognostic and Therapeutic Marker of HTLV-1-Associated Adult T Cell Leukemia/Lymphoma

Infection with human T-lymphotropic virus 1 (HTLV-1) can lead to severe diseases, including adult T-cell leukemia/lymphoma (ATL), for which current therapies are inadequate. HTLV-1 persists chronically through integration of its genome into host DNA and expansion of infected clones via cellular proliferation. Selective elimination of infected cells is the ideal treatment goal but requires identifying cellular markers dysregulated by HTLV-1 that can be exploited therapeutically. Combining metabolomics and proteomics analyses, we identified increased expression of the mitochondrial enzyme ferredoxin reductase (FDXR) as a hallmark of HTLV-1-infected cells. In patient cells, FDXR upregulation mirrored disease severity, was enriched in proliferating tumour cells and predicted worse ATL prognosis. Mechanistically, FDXR upregulation was directly driven by the transactivating isoforms of two p53 family members, TAp63 and TAp73. In silico drug susceptibility predictions, followed by targeted cytotoxicity, proliferation and Drug-Seq assays demonstrated that FDXR upregulation is associated with increased sensitivity of ATL cells to repurposed chemotherapeutic agents, particularly fluorouracil. Overall, our findings establish FDXR as a novel biomarker of HTLV-1-associated disease progression and ATL prognosis, elucidate its upstream molecular regulation, and highlight its predictive potential for chemotherapeutic sensitivity of ATL cells.

microbiology↗

bioRxiv2025

Metagenomic enables the first detection of Trypanosoma sp. in Streblidae (Diptera: Hippoboscoidea) parasitizing bats in Sao Paulo, Brazil.

Bats play important ecological roles but also can carry various pathogens, including trypanosomatids. This study reports the first detection of Trypanosoma sp. in flies from the Streblidae family parasitizing Carollia perspicillata bats in a peri-urban fragment of the Atlantic Forest in Sao Paulo. Using shotgun metagenomics, we detected Trypanosoma sequences in half of the fly samples analyzed. Phylogenetic analysis showed these sequences belong to the Neobat 4 clade, previously reported in Carollia sp. bats. Although streblid flies ability to transmit Trypanosoma is still unknown, their close connection with bats means they might be used as a non-invasive way to monitor pathogens when bat sampling is difficult. More research is needed, but this work expands what we know about the Neobat 4 clades geographic distribution and parasite circulation in bats and their ectoparasites.

microbiology↗

bioRxiv2023

Lessons from a multilaboratorial task force for diagnosis of a fatal toxoplasmosis outbreak in captive primates in Brazil

As exemplified by the Coronavirus Disease 2019 (COVID-19) pandemic, infectious diseases may emerge and spread rapidly, often causing serious economic losses and public health concerns. In fact, disease outbreaks have become increasingly common, especially those of zoonotic origin. The Brazilian Ministry of Health is responsible for national epizootic surveillance. However, the systems focus primarily on diseases affecting humans has led to the neglect of other zoonotic diseases. In this report, we present an integrated investigation of an outbreak that occurred during the first year of the COVID-19 pandemic among captive neotropical primates housed at a primatology center in Brazil. After presenting a range of non-specific clinical signs, including fever, prostration, inappetence, and abdominal pain, ten primates from five different species died within approximately four days. Despite the state of health emergency due to the pandemic, a network of volunteer researchers was established to investigate the outbreak. A wide range of high-resolution techniques was used for different pathogens, including SARS-CoV-2 (RTq-PCR, ELISA and IHC), Toxoplasma gondii (IHC and IFA) and Escherichia coli (IFA), as well as a portable Metagenomic Sequencing utilizing Nanopore Technology. Within a span of four days after necropsies, we successfully identified T. gondii as the causative agent of this outbreak. This case highlights some of the obstacles faced with the current Brazilian surveillance system, which is still limited. A cross-platform interdisciplinary investigation could be a possible model for future epizootic investigations in non-human animals. Author summaryThe Brazilian epizootic surveillance system, under the regulation of the Ministry of Health, has been established to address a national list of compulsory notifiable diseases. However, focusing mainly on the risks to humans causes other zoonoses to be neglected. Here we present an outbreak that occurred during the first year of the COVID-19 pandemic that affected eleven neotropical primates (NP) belonging to six different species. Within four days of exhibiting a range of non-specific clinical signs, including fever, prostration, inappetence, and abdominal pain, ten NPs died. Despite testing negative for pathogens included in the national surveillance policy, a collaborative group of researchers investigated the outbreak in detail. Using integrated diagnostic techniques, we identified Toxoplasma gondii as the causative agent four days after necropsy. Toxoplasmosis causes devastating acute death outbreaks in neotropical primates and is currently absent in the national guidelines. This unified effort proved the effectiveness of a multidisciplinary collaborative surveillance network in facilitating precise diagnoses.

microbiology↗

bioRxiv2019

Early identification of dengue virus lineage replacement in Brazil using portable genomic surveillance

Over 400 million people are estimated to be at risk of acquiring dengue virus (DENV). Despite efforts to mitigate the impact of DENV epidemics, the virus remains a public health problem in the Americas: more than one million DENV cases were reported in the continent between January and July 2019 DENV was first detected in Brazil in 1982, and Brazil has reported 88% (1,127,244 cases) of all DENV cases in the Americas during 2019 to date. Sao Paulo state in the southeast of Brazil has reported nearly half of all DENV infections in the country. Here we characterised the genetic diversity of DENV strains circulating in Sao Paulo state in 2019, at the epicentre of the ongoing DENV epidemic. Using portable nanopore sequencing we generated 20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities, Araraquara and Sao Jose do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Notably, phylogenetic analysis indicated that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Our genetic analysis further indicates that the introduction and onwards spread of the outbreak lineage (named here DENV2-III BR-4) indicates a new DENV2 lineage replacement in Brazil. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.\n\nAuthor SummaryDengue is the most important mosquito-borne viral disease of humans. The disease is caused by the dengue virus (DENV) that is classified within genus Flavivirus. DENV infections are caused by 4 serotypes (DENV 1-4) that are genetically related but antigenically distinct. Dengue infection results in a variety of symptoms that range from mild fever to dengue hemorrhagic fever and/or dengue shock syndrome (DHF/DSS). Clinical outcomes are associated with different types of infection, viral serotypes, genotypes, lineages, and host genetic factors. As a re-emerging infectious disease, DENV has become a serious threat to public health in the Americas, and particularly in Brazil, where it was introduced in the 1980s and became well established due to the country-wide re-infestation of the Aedes aegypti mosquito vector species. During the first six months of 2019, 1,282,183 DENV cases were reported in the Americas, with Brazil reporting a staggering 1,127,244 (88%) of all dengue cases in the continent. To date, no information exists on the genetic composition of the DENV lineage or lineages causing the current epidemic. Here we use portable sequencing to rapidly generate virus genome data from cases occurring in two different are severely-affected municipalities in Sao Paulo state, Brazil. We find that the 2019 dengue outbreak in Brazil is caused by a newly introduced DENV serotype 2 genotype III (Asian/American) that seems to be replacing previously-circulating DENV2 lineages. We discuss the potential implications of our results regarding the current outbreak in the context of previous outbreaks in the same region.

genomics↗

bioRxiv2019

HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS / MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases. Here the expression of Endogenous retroviruses K and W (HERV-K and HERV-W) was determined in blood from moderately and severely affected ME/CFS patients. HERV-K was overexpressed only in moderately affected individuals and HERV-W showed no difference. This is the first report about HERV-K differential expression in moderate ME/CFS.

molecular biology↗

bioRxiv2019

Use of an automated pyrosequencing technique for confirmation of Sickle Cell Disease

BackgroundThe diagnosis of sickle cell disease (SCD) is made by hemoglobin assays such as high-performance liquid chromatography (HPLC), isoelectric focusing and cellulose acetate or citrate agar electrophoresis. These assays are easy to perform and used in large-scale newborn screening in many countries. These tests however may not easily differentiate S{beta}0 thalassemia from SS or identify other hemoglobin variants, and in this case, hemoglobin (HBB) gene sequencing may be necessary.\n\nObjectivesTo develop a high throughput DNA based confirmatory assay for SCD and to detect mutations in the HBB gene.\n\nMethodsWe developed an automated pyrosequencing technique (PyS) based on QIAGEN technology (Hilden, Germany) to detect homozygous or heterozygous hemoglobin S mutations as well as hemoglobin C mutations. The technique was tested on 2,748 samples from patients enrolled in a multi-center SCD cohort in Brazil. Patients were previously tested using HPLC to diagnose SCD as part of routine clinical care. Any subjects with discrepant results between HPLC and PyS or with heterozygous hemoglobin S detected had Sanger sequencing of the HBB gene.\n\nResultsWe identified 168 samples with discrepant results between HPLC and PyS and 100 with concordant HPLC and PyS= heterozygous S, which would suggest S{beta}-thalassemia or other hemoglobin S variants. The PyS assay correctly identified 1906 (98.7%) of the 1930 HbSS and 628 (98.7%) of the 636 HbSC samples. Of the 179 remaining samples, PyS correctly indicated S heterozygosis in 165 (92.2%). Of the 165 heterozygous S samples confirmed by Sanger as consistent with S{beta} thalassemia genotype, 84 samples were classified as S{beta}0 thalassemia and 81 as S{beta}+ thalassemia. The most frequent beta thalassemia mutations of S{beta}0 and S{beta}+ were HBB: c.118C>T (Gln40Stop) and HBB c.92 + 6T> C, respectively.\n\nDiscussionThe PyS proved to be satisfactory for large-scale confirmatory testing of hemoglobin mutation. Moreover, with this study we were able to describe the most common {beta}+ and {beta}0 mutations in SCD patients with S{beta}-thalassemia in a large multi-institutional SCD cohort in Brazil.

molecular biology↗

bioRxiv2017

Emergence and persistence of the Chikungunya virus East-Central-South-African genotype in Northeast Brazil

We investigate an outbreak of exanthematous illness in Maceio, Alagoas, using molecular surveillance. Of 273 samples, 76% tested RT-qPCR positive for Chikungunya virus. Phylogenetic analysis reveals that the outbreak was caused by the East-Central-South-African genotype, and that this lineage has likely persisted since mid-2014 in Northeast Brazil.\n\nArticle summary lineTransmission of the Chikungunya virus East-Central-South-African genotype has been ongoing in the Northeast region of Brazil since mid-2014.

epidemiology↗

bioRxiv2017

Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples

Genome sequencing has become a powerful tool for studying emerging infectious diseases; however, genome sequencing directly from clinical samples without isolation remains challenging for viruses such as Zika, where metagenomic sequencing methods may generate insufficient numbers of viral reads. Here we present a protocol for generating coding-sequence complete genomes comprising an online primer design tool, a novel multiplex PCR enrichment protocol, optimised library preparation methods for the portable MinION sequencer (Oxford Nanopore Technologies) and the Illumina range of instruments, and a bioinformatics pipeline for generating consensus sequences. The MinION protocol does not require an internet connection for analysis, making it suitable for field applications with limited connectivity. Our method relies on multiplex PCR for targeted enrichment of viral genomes from samples containing as few as 50 genome copies per reaction. Viral consensus sequences can be achieved starting with clinical samples in 1-2 days following a simple laboratory workflow. This method has been successfully used by several groups studying Zika virus evolution and is facilitating an understanding of the spread of the virus in the Americas.

genomics↗