Biology subjects

Conceicao, H. B.

Publications and source records attributed to Conceicao, H. B..

3 recordsLinked to original sources

bioRxiv2023

Sandy: A user-friendly and versatile NGS simulator to facilitate sequencing assay design and optimization

Next-generation sequencing (NGS) is currently the gold standard technique for large-scale genome and transcriptome studies. However, the downstream processing of NGS data is a critical bottleneck that requires difficult decisions regarding data analysis methods and parameters. Simulated or synthetic NGS datasets are practical and cost-effective alternatives for overcoming these difficulties. Simulated NGS datasets have known true values and provide a standardized scenario for driving the development of data analysis methodologies and tuning cut-off values. Although tools for simulating NGS data are available, they have limitations in terms of their overall usability and documentation. Here, we present Sandy, an open-source simulator that generates synthetic reads that mimic DNA or RNA next-generation sequencing on the Illumina, Oxford Nanopore, and Pacific Bioscience platforms. Sandy is designed to be user-friendly, computationally efficient, and capable of simulating data resembling a wide range of features of real NGS assays, including sequencing quality, genomic variations, and gene expression profiles per tissue. To demonstrate Sandys versatility, we used it to address two critical questions in designing an NGS assay: (i) How many reads should be sequenced to ensure unbiased analysis of gene expression in an RNA sequencing run? (ii) What is the lowest genome coverage required to identify most (90%) of the single nucleotide variants and structural variations in whole-genome sequencing? In summary, Sandy is an ideal tool for assessing and validating pipelines for processing, optimizing results, and defining the costs of NGS assays. Sandy runs on Linux, MacOS, and Microsoft Windows and can provide feasible results, even on personal computers. Availability: Sandy is freely available at https://galantelab.github.io/sandy.

bioinformatics↗

bioRxiv2023

Retro-miRs: Novel and functional miRNAs originated from mRNA retrotransposition

BackgroundReverse transcribed gene copies, or retrocopies, have emerged as a major source of evolutionary novelties. MicroRNAs (miRNAs) are small, highly conserved RNAs molecules among species that serve as key post-transcriptional regulators of gene expression. The birth and subsequent evolution of miRNAs have been addressed, but not fully. ResultsIn this study, we carried out a comprehensive investigation of miRNAs origination through retroduplicated mRNA sequences (retrocopies). We identified 17 retroduplicated miRNAs (retro-miRs) that emerged from mRNAs retrocopies. Four of these retro-miRs had de novo origination within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and were duplicated along with their host mRNAs. We found that retro-miRs are primates specific, including 5 retro-miRs conserved among all primates and two human-specific retro-miRs. All of the retro-miRs were expressed and had predicted and experimentally validated target genes, with the exception of miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes, such as metabolic processes, cell signaling and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs have a potential oncogenic role in cancer, targeting key cancer genes and being overexpressed in several cancer types, including Liver Hepatocellular Carcinoma and Stomach Adenocarcinoma. ConclusionOur findings demonstrate that mRNAs retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play roles in cancer.

genomics↗

bioRxiv2022

The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes

The exon junction complex (EJC) plays key roles throughout the lifespan of RNA and is particularly relevant in the nervous system. We investigated the roles of two EJC members, the paralogs MAGOH and MAGOHB, with respect to brain tumor development. High MAGOH/MAGOHB expression was observed in 14 tumor types; glioblastoma (GBM) showed the greatest difference compared to normal tissue. Increased MAGOH/MAGOHB expression was associated with poor prognosis in glioma patients, while knockdown of MAGOH/MAGOHB affected different cancer phenotypes. Reduced MAGOH/MAGOHB expression in GBM cells caused alterations in the splicing profile, including re-splicing and skipping of multiple exons. The binding profiles of EJC proteins indicated that exons affected by MAGOH/MAGOHB knockdown accumulated fewer complexes on average, providing a possible explanation for their sensitivity to MAGOH/MAGOHB knockdown. Transcripts (genes) showing alterations in the splicing profile are mainly implicated in cell division, cell cycle, splicing, and translation. We propose that high MAGOH/MAGOHB levels are required to safeguard the splicing of genes in high demand in scenarios requiring increased cell proliferation (brain development and GBM growth), ensuring efficient cell division, cell cycle regulation, and gene expression (splicing and translation). Since differentiated neuronal cells do not require increased MAGOH/MAGOHB expression, targeting these paralogs is a potential option for treating GBM.

cancer biology↗