Biology subjects

Ruiz, J. L.

Publications and source records attributed to Ruiz, J. L..

5 recordsLinked to original sources

bioRxiv2026

Influenza A virus NS1 sequesters RNA:DNA hybrids to evade RNase H1-dependent innate immunity

RNA:DNA hybrids, and their aberrant accumulation, are key regulators of human genome integrity and innate immunity. Given the functional parallels and extensive interplay between the human genome and viral genetic material, RNA:DNA hybrids also have established roles during infections with DNA viruses and retroviruses. Nevertheless, the presence and consequences of RNA:DNA hybrids in RNA virus infections, which lack a DNA phase, remain largely uncharacterized. Here, we show that infection of human cells with influenza A virus (IAV), but not several other respiratory negative-sense RNA viruses, induces the unexpected accumulation of RNA:DNA hybrids in perinuclear regions. Sequencing of infection-induced cytoplasmic RNA:DNA hybrids revealed that they derive predominantly from the human host genome, with apparent preference for intronic and intergenic sequences, although an intriguing fraction also originates from the IAV genome, with some enrichment for specific viral segments. Notably, we identify the IAV non-structural protein, NS1, as a key determinant of RNA:DNA hybrid localization and stability: NS1 is required for, and co-localizes with, perinuclear RNA:DNA hybrids, and its absence appears to sensitize RNA:DNA hybrids to metabolism by the cellular ribonuclease, RNase H1. Furthermore, experimental loss of RNase H1 attenuates IAV-induced antiviral responses, including type I interferon and inflammatory gene expression programs, indicating that RNA:DNA hybrid metabolism likely contributes to host defense. Overall, our findings uncover host- and viral-origin RNA:DNA hybrids as a previously unrecognized feature of a human pathogenic RNA virus infection, and suggest a mechanism by which a viral product antagonizes host responses mediated via these unusual nucleic acids by spatial sequestration.

immunology↗

bioRxiv2025

The dynamic transcriptome of Plasmodium malariae in the mosquito

To survive and multiply in different host niches, malaria parasites require sets of proteins that are expressed during the life cycle in a timely manner. Plasmodium malariae is a human malaria parasite that is present in most malaria-endemic regions. However, this species remains enigmatic because it is very challenging to culture, its low parasitaemia in human infections, and frequent co-infection with other malarias. We investigate the transcriptome of P. malariae during transmission in the vector by analyzing RNA-seq data from midgut and salivary gland parasite stages obtained in two experimental mosquito infections with field P. malariae isolates. Our analysis resulted in 3,699 expressed genes, of which 263 are developmentally regulated and 1,338 are P. malariae specific, including genes with unknown functions and without orthologs in other Plasmodium. We detected unique expression patterns of the ApiAP2 family of transcription factors, many of which appear to function as master regulators during sporogony. We found expressed several members of multigene families, like PIR, PHIST, fam-l, and described new families potentially showing transcriptional heterogeneity. Our findings point to the uniqueness of the P. malariae transcriptome, probably related to different transmission traits in the vector, and the lower pathogenicity and virulence in the human.

microbiology↗

bioRxiv2023

reanalyzerGSE: tackling the everlasting lack of reproducibility and reanalyses in transcriptomics

SummaryIn the current context of transcriptomics democratization, there is an unprecedented surge in the number of studies and datasets. However, advances are hampered by aspects such as the reproducibility crisis, and lack of standardization, in particular with scarce reanalyses of secondary data. reanalyzerGSE, is a user-friendly pipeline that aims to be an all-in-one automatic solution for locally available transcriptomic data and those found in public repositories, thereby encouraging data reuse. With its modular and expandable design, reanalyzerGSE combines cutting-edge software to effectively address simple and complex transcriptomic studies ensuring standardization, up to date reference genome, reproducibility, and flexibility for researchers. Availability and implementationThe reanalyzerGSE open-source code and test data are freely available at both https://github.com/BioinfoIPBLN/reanalyzerGSE and 10.5281/zenodo.XXXX under the GPL3 license. Supplementary data are available.

bioinformatics↗

bioRxiv2021

From contigs to chromosomes: automatic Improvement of Long Read Assemblies (ILRA)

Recent advances in long read technologies not only enable large consortia to aim to sequence all eukaryotes on Earth, but they also allow individual laboratories to sequence their species of interest with relatively low investment. Although there is a promise of long read technologies to obtain "perfect genomes", the number of contigs often exceeds the number of chromosomes by far, containing many insertion and deletion errors around homopolymer tracks. To overcome these issues, we implemented the ILRA pipeline to correct long read-based assemblies, so contigs are reordered, renamed, merged, circularized, or filtered if erroneous or contaminated, and Illumina reads are used to correct homopolymer errors. We successfully tested our approach by improving the genomes of Trypanosoma brucei and Leptosphaeria spp, and generated four novel Plasmodium falciparum assemblies from field samples. We found that correcting homopolymer tracks reduced the number of genes incorrectly annotated as pseudogenes, but an iterative correction seems to be required to correct larger numbers of sequencing errors. In summary, we described and compared the performance of our new tool, which improved the quality of novel long read assemblies of genomes up to 1Gbp. AvailabilityThe tool is available at GitHub: https://github.com/ThomasDOtto/ILRA.

bioinformatics↗

bioRxiv2020

The regulatory genome of the malaria vector Anopheles gambiae: integrating chromatin accessibility and gene expression

Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about mechanisms of transcriptional regulation. We profiled chromatin accessibility by ATAC-seq in laboratory-reared An. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that annotate to mosquito immune-response genes. This study is important not only for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but the information is of great potential for developing new mosquito-control and anti-malaria strategies.

genomics↗