Biology subjects

Jovel, J.

Publications and source records attributed to Jovel, J..

4 recordsLinked to original sources

bioRxiv2023

Proportionality-based association metrics in count compositional data

MotivationCompositional data comprise vectors that describe the constituent parts of a whole. Data arising from various -omics platforms such as 16S and RNA-sequencing are compositional in nature. However, correlations between features on raw counts have no meaningful interpretation. Metrics of proportionality were formulated to address this problem. However, there is an inherent bias that arises when calculating these metrics empirically on count-based measures due to variability in read depths. ResultsWe quantify the bias introduced by empirically calculating proportionality-based association metrics in count data. Additionally, we propose a means of estimating these metrics within a logit-normal multinomial model in pursuit of more accurate estimates. The model-based estimates are shown to outperform empirical estimates in simulated data, and are additionally applied to a mouse embryonic stem-cell single-cell sequencing dataset as well as a pediatric-onset multiple sclerosis metagenomic dataset. Availability and ImplementationAn R package is available at https://CRAN.R-project.org/package=countprop. Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2020

Diagnostic of begomoviruses in complex infections -a case study

Complexes of viruses inducing a syndrome in plants strongly hinder the identification of the causal agent of a disease. The Sida micrantha mosaic disease is associated with a complex of begomoviruses. For more than twenty years, two DNAs A (DNA A2 and DNA A3) belonging to this complex could neither be detected nor isolated from Sida micrantha Schr. plants, although one of them (DNA A2) now appears to be the major component of the complex. A random unintended Bemisia tabaci-mediated transmission of begomoviruses from several Sida species - including S. micrantha - to experimental Malva parviflora plants resulted in the serendipitous finding of these new DNAs A. Simultaneously, a number of other begomoviruses infecting Sida plants from several Latin American countries were transmitted to M. parviflora plants and the convergence of them resulted in natural pseudorecombinants. Pseudorecombination, however, took place exclusively between heterologous genomic components that shared identical binding sites for the replication-associated protein AC1. This case study constitutes an exceptional opportunity for the analysis of plant-virus- vector interactions in a quasi-natural environment. In addition to that, the methodology described here may be used to isolate and characterize different begomoviruses inducing a syndrome during mix infections.

molecular biology↗

bioRxiv2019

CD71+ erythroid cells exacerbate HIV-1 infection by reactive oxygen species and trans-infect HIV to CD4+ T cells

CD71+ erythroid cells (CECs) have a wide range of immunomodulatory properties but their potential role in HIV has never been investigated before. Here, we demonstrate that CECs are abundant in the human cord blood, placental tissue and peripheral blood of pregnant mothers. We found that CECs exacerbate HIV-1 infection/replication when co-cultured with CD4+ T cells; and that pre-exposure of CD4+ T cells to CECs make them more permissible to HIV-infection. Our observations indicate how interactions of CECs with CD4+ T cells via reactive oxygen species (ROS)-dependent mechanism results in the upregulation of NF-kB, which affects the cell cycle machinery to facilitate HIV-1 replication. We found the complement receptor-1 (CD35) and the Duffy antigen receptor for chemokines (DARC) as potential HIV-target molecules are expressed significantly higher on CECs compared to mature red blood cells. However, blocking CD35 or DARC did not inhibit HIV-1 trans-infection to uninfected CD4+ T cells. We demonstrate that CECs bind to HIV-1 via CD235a and subsequently trans-infect the virus to uninfected CD4+ T cells. In addition, we found significant abundance of CECs in the blood of HIV-1 infected and anemic subjects, which enhanced HIV infection/replication in autologous CD4+ T cells similar to what we observed for the cord blood and placenta-derived CECs. In agreement, a positive correlation between the frequency of CECs with the plasma viral load in HIV-1 infected antiretroviral therapy naive individuals was observed. In addition, we found that CECs even in the presence of Tenofovir, can trans-infect HIV-1 to CD4+ T cells. Our studies provide a novel insight into the role of CECs in HIV pathogenesis as potential contributing cells for viral persistence in the presence of antiretroviral therapy.\n\nAuthor summaryDespite current antiretroviral therapy, HIV-1 persists in a small pool of infected cells. A better understanding of HIV-reservoirs and influence of other non-immune cells on HIV-1 replication and transmission is a pre-requisite to the development of HIV-eradication strategies. Immature red blood cells (CD71+ erythroid cells) are physiologically abundant in newborns, cord blood, placenta and blood of pregnant women, with a wide range of immunological properties. This study demonstrates that these cells not only enhance HIV-1 infection/replication by reactive oxygen species in HIV-target cells (CD4+ T cells) but also bind to HIV and trans-infect the virus to the target cells in the presence of Tenofovir, an HIV drug.\n\nWe found that these immature red blood cells are abundant in the blood of HIV-patients and anemic individuals. In addition, we observed a positive correlation between the levels of plasma viral load with the frequency of immature red blood cells in HIV-infected individuals. Therefore, our studies discover a novel role for these immature red blood in HIV pathogenesis, which encourages efforts to target these cells as adjuncts of current treatment strategies.

immunology↗

bioRxiv2017

Novel insights into the molecular heterogeneity of hepatocellularcarcinoma

Hepatocellular carcinoma (HCC) is influenced by numerous factors, which results in diverse genetic, epigenetic and transcriptional scenarios, thus posing obvious challenges for disease management. We scrutinized the molecular heterogeneity of HCC with a multi-omics approach in two small cohorts of resected and explanted livers. Whole-genome transcriptomics was conducted, including polyadenylated transcripts and micro (mi)-RNAs. Copy number variants (CNV) were inferred from whole genome low-pass sequencing data. Fifty-six cancer-related genes were screened using an oncology panel assay. HCC was associated with a dramatic transcriptional deregulation of hundreds of protein-coding genes suggesting downregulation of drugs catabolism, induction of inflammatory responses, and increased cell proliferation in resected livers. Moreover, several long non-coding RNAs and miRNAs not reported previously in the context of HCC were found deregulated. In explanted livers, downregulation of genes involved in energy-producing processes and upregulation of genes aiding in glycolysis were detected. Numerous CNV events were observed, with conspicuous hotspots on chromosomes 1 and 17. Amplifications were more common than deletions, and spanned regions containing genes potentially involved in tumorigenesis. CSF1R, FGFR3, FLT3, NPM1, PDGFRA, PTEN, SMO and TP53 were mutated in all tumors, while other 26 cancer-related genes were mutated with variable penetrance. Our results highlight a remarkable molecular heterogeneity between HCC tumors and reinforce the notion that precision medicine approaches are urgently needed for cancer treatment. We expect that our results will serve as a valuable dataset that will generate hypotheses for us or other researchers to evaluate to ultimately improve our understanding of HCC biology.

cancer biology↗