Project description:The development of precision medicine strategies requires prior knowledge of the genetic background of the target population. However, despite the availability of data from admixed Americans within large reference population databases, we cannot use these data as a surrogate for that of the Brazilian population. This lack of transferability is mainly due to differences between ancestry proportions of Brazilian and other admixed American populations. To address the issue, a coalition of research centres created the Brazilian Initiative on Precision Medicine (BIPMed), an initiative of five Research Innovation and Dissemination Centers (RIDCs) supported by FAPESP.
Project description:Zoonotic influenza A viruses of avian origin can cause severe disease in individuals, or even global pandemics, and thus pose a threat to human populations. Waterfowl and shorebirds are believed to be the reservoir for all influenza A viruses, but this has recently been challenged by the identification of novel influenza A viruses in bats. The major bat influenza A virus envelope glycoprotein, haemagglutinin, does not bind the canonical influenza A virus receptor, sialic acid or any other glycan, despite its high sequence and structural homology with conventional haemagglutinins. This functionally uncharacterized plasticity of the bat influenza A virus haemagglutinin means the tropism and zoonotic potential of these viruses has not been fully determined. Here we show, using transcriptomic profiling of susceptible versus non-susceptible cells in combination with genome-wide CRISPR-Cas9 screening, that the major histocompatibility complex class II (MHC-II) human leukocyte antigen DR isotype (HLA-DR) is an essential entry determinant for bat influenza A viruses. Genetic ablation of the HLA-DR α-chain rendered cells resistant to infection by bat influenza A virus, whereas ectopic expression of the HLA-DR complex in non-susceptible cells conferred susceptibility. Expression of MHC-II from different bat species, pigs, mice or chickens also conferred susceptibility to infection. Notably, the infection of mice with bat influenza A virus resulted in robust virus replication in the upper respiratory tract, whereas mice deficient for MHC-II were resistant. Collectively, our data identify MHC-II as a crucial entry mediator for bat influenza A viruses in multiple species, which permits a broad vertebrate tropism.
Project description:This study aimed to investigate the heat tolerance and inheritance patterns of leukocyte transcriptomics in F1 hybrid cattle (AN♂ × DR♀) and their parents Red Angus (AN) and Droughtmaster (DR) under heat stress.
Project description:The aim of this study was to perform a genomic profiling of gliomas of Brazilian origin, using array-CGH, MSI analysis and to associate the genomic alterations with TERT and IDH1 mutation status, and correlate the molecular features with clinicopathological characteristics.
Project description:Background: Transcriptomic variation among cattle breeds and their crossbreds may help to better understanding of consequences of crossbreeding and heterosis. In this study the differences in biological functions and pathways of three crossbreds including 50 and 75 percent Holstein were compared with their purebred parents, Holstein and Taleshi (an indigenous breed) cattle. Results: Five populations and their ten comparisons were studied by bioinformatics tools for transcriptome analysis. We pooled blood RNA of at least 8 animals of each population prior to RNA sequencing. The obtained results showed that total expressed transcripts in all populations were 72,812 with 22,627 annotated genes. Functional analysis of differentially expressed genes (DEGs) showed that the genetics information processing and metabolism were the most highly-impacted pathways. Among all significantly enriched pathways, eukaryotic translation initiation factor-2 signaling had the highest activation z-score (5.3) in crossbred compared to purebred cattle. The majority of upstream regulators of genes including transcription regulators and cytokines were differentially expressed among populations in which their activation z-score in purebred was more than crossbred cattle. Conclusions: Crossing of Holstein with Taleshi breed resulted in higher activity of pathways related to genetic information processing and lower activity of pathways related to immunity and inflammatory responses. To the best of our knowledge, this is the first study where the differences in pathways and functions were studied using high throughput sequencing of blood in a cattle crossbreeding program. The analysis revealed that the most important differences between studied genotypes, especially between purebred and crossbred cattle, were related to immune functions and metabolism.
Project description:MicroRNA-sequencing of the bone marrow samples from Brazilian pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL).
Project description:Herein, we aimed to analyze the gene expression profile of medulloblastoma samples from a Brazilian cohort of 17 pediatric patients.