Biology subjects

Avina-Padilla, K.

Publications and source records attributed to Avina-Padilla, K..

3 recordsLinked to original sources

bioRxiv2022

Discovering hub genes involved in the pathophysiological impact of COVID-19 on diabetes kidney disease by differential gene expression and interactome analysis

Diabetic kidney disease (DKD) is a frequently chronic kidney pathology derived from diabetes comorbidity. This condition has irreversible damage, and its risk factor increases with SARS-CoV-2 infection. The prognostic outcome for diabetic patients with COVID-19 is dismal, even with intensive medical treatment. However, there is still scarce information on critical genes involved in the pathophysiological impact of COVID-19 on DKD. Herein, we characterize differential expression gene (DEG) profiles and determine hub genes undergoing transcriptional reprogramming in both disease conditions. Out of 995 DEGs, we identified 42 DEGs shared with COVID-19 pathways. Enrichment analysis elucidated that they are significantly induced with implications for immune and inflammatory responses. By performing a protein-protein interaction (PPI) network and applying topological methods, we determine the following five hub genes STAT1, IRF7, ISG15, MX1, and OAS1. Then, by network deconvolution, we determine their co-expressed gene modules. Moreover, we validate the conservancy of their upregulation using the Coronascape database (DB). Finally, tissue-specific regulation of the five predictive hub genes indicates that OAS1 and MX1 expression levels are lower in healthy kidney tissue. Altogether, our results suggest that these genes could play an essential role in developing severe outcomes of COVID-19 in DKD patients.

bioinformatics↗

bioRxiv2022

Deciphering the tissue-specific regulatory role of intronless genes across cancers

Intronless genes (IGs) or single-exon genes lacking an intron are found across most Eukaryotes. Notably, IGs display a higher transcriptional fidelity as they are not regulated through alternative splicing, suggesting better predictability biomarkers and easier regulation as targets for therapy. Cancer is a complex disease that relies on progressive uncontrolled cell division linked with multiple dysfunctional biological processes. Tumor heterogeneity remains the most challenging feature in cancer diagnosis and treatment. Given the clinical relevance of IGs, we aim to identify their unique expression profiles and interactome, that may act as functional signatures across eight different cancers. We identified 940 protein-coding IGs in the human genome, of which about 35% were differentially expressed across the analyzed cancer datasets. Specifically, [~]78% of differentially expressed IGs were undergoing transcriptional reprogramming with elevated expression in tumor cells. Remarkably, in all the studied tumors, a highly conserved induction of a group of deacetylase-histones located in a region of chromosome 6 enriched in nucleosome and chromatin condensation processes. This study highlights that differentially expressed human intronless genes across cancer types are prevalent in epigenetic regulatory roles participating in specific PPI networks for ESCA, GBM, and LUAD tumors. We determine that IGs play a key role in the tumor phenotype at transcriptional and post-transcriptional levels, with important mechanisms such as interactomics rewiring.

genomics↗

bioRxiv2021

Evolutionary Perspective And Expression Analysis Of Intronless Genes Highlight The Conservation On Their Regulatory Role

Eukaryotic gene structure is a combination of exons generally interrupted by intragenic non-coding DNA regions termed introns removed by RNA splicing to generate the mature mRNA. Thus, eukaryotic genes can be either single exon genes (SEGs) or multiple exon genes (MEGs). Among SEGs, intronless genes (IGs) are a subgroup that additionally lacks introns at their UTRs, and code for proteins essentially involved in development, growth, and cell proliferation. Gene expression of IGs has been proposed to be highly specialized for neuro-specific functions and linked to cancer, neuropathies, and developmental disorders. The abundant presence of introns in eukaryotic genomes is pivotal for the precise control of gene expression. Notwithstanding, IGs exempting splicing events entail a higher transcriptional fidelity, making them even more valuable for regulatory roles. This work aimed to infer the functional role and evolutionary history of IGs using the mouse genome. Intronless protein-coding genes consist of a subgroup of ~6 % of a total of 21,527 genes with one exon. To understand the prevalence, biological relevance, and evolution, we identified and studied their 1,116 functional proteins. We validated differential expression in transcriptomics data of early embryo stages using mouse telencephalon tissue. Our results showed that expression levels of IGs are lower compared to MEGs. However, strongly upregulated IGs include transcription factors (TFs) such as the class 3 of POU (HMG Box), Neurog1, Olig1, and BHLHe22, BHLHe23, among other essential genes including the beta cluster of protocadherins. Most striking was the finding that IG-encoded BHLH TFs qualify the criteria to be referred to as microprotein candidates. Finally, predicted protein orthologs in other six genomes confirmed a high conservancy of IGs associated with regulating neurobiological processes and with chromatin organization and epigenetic regulation in Vertebrata. Moreover, this study highlights that IGs are essential modulators of regulatory processes, as Wnt signaling pathway and biological processes as pivotal as sensory organs developing at a transcriptional and post-translational level. Overall, our results suggest that IG proteins have specialized, prevalent, and unique biological roles and that functional divergence between IGs and MEGs is likely to be the result of specific evolutionary constraints.

evolutionary biology↗