Biology subjects

Barberan-Soler, S.

Publications and source records attributed to Barberan-Soler, S..

3 recordsLinked to original sources

bioRxiv2025

A method of comprehensive sequencing analysis of the small RNA fragmentome (RiboMarker)

Circulating cell-free nucleic acids (cfDNA and cfRNA) found in blood and other biofluids are promising biomarkers for cancer. However, current methods exploiting tumor-derived cfDNA (ctDNA) are not sensitive enough in detecting minimal residual disease and early stages of cancer when it is more treatable. Small RNAs and RNA fragments (sRNA) can potentially provide higher detection sensitivity and specificity than ctDNA. Sequencing analysis of the variety of sRNAs representing the entire RNA fragmentome would improve our understanding of their roles in cancer development and help to discover novel sRNA biomarkers for cancer diagnostics and personalized treatments. However, conventional methods of sRNA-Seq library preparation are limited to detection of sRNA with 5-P and 3-OH ends that represent only less than 10% of the whole RNA fragmentome, whereas sRNAs having different phosphorylation statuses (P or OH) of their termini are hidden. Although recently developed sRNA-Seq methods allow detection of most sRNA (including the hidden ones) simultaneously, these methods cannot both detect and distinguish among the individual RNAs with differing termini combinations (RNA Types). Here we describe the RiboMarker(R) platform for preparation of sRNA sequencing libraries that addresses these shortcomings. It uses distinctive enzymatic pretreatment(s) of RNA samples that can both detect all and enrich for individual sRNA Types upfront of sequencing library preparation. The RiboMarker(R) platform has the potential capability to both identify and detect with enhanced sensitivity low abundance sRNA biomarkers of specific RNA classes and their termini.

molecular biology↗

bioRxiv2025

Characterization of transcriptomic changes across Coccidioides morphologies using RiboMarker(R)-enhanced RNA sequencing

Coccidioides is a dimorphic, pathogenic fungus responsible for transmission of the mammalian disease colloquially known as "Valley fever". To better understand the molecular basis of Coccidioides pathogenesis, previous studies have characterized transcriptomes that define transitions between the saprobic and pathogenic life stages of the two species that cause Valley fever - Coccidioides immitis and Coccidioides posadasii. However, none of these studies have focused on small RNA profiles, which have been shown in several pathogenic fungi to play crucial roles in host-pathogen communication, affecting virulence and infectivity. In this study, we analyzed changes in small RNA expression across three major morphologies of C. posadasii: arthroconidia, mycelia, and spherules, from both intracellular and extracellular fractions. Utilizing RiboMarker(R) small RNA and RNA fragment library preparation, we show enhanced coverage across the transcriptome by increasing incorporation of normally incompatible RNAs into the sequencing pool. Using these data, we observed transcriptomic shifts during the transition of arthroconidia to either mycelia or spherules, marked largely by changes in both protein-coding, tRNA, and unannotated loci. As little is known regarding the mechanisms governing these life stage transitions, these data provide better insight into those small RNA- and fragment-producing genes and loci that may be required for progression between Coccidioides saprobic and parasitic life cycles. Additionally, analysis of fragmentation patterns across all morphologies suggests unique patterns of RNA fragmentation across a cohort of RNA species that correlate with a given ecotype. Finally, we noted evidence of RNA export to the extracellular space, particularly regarding snRNA and tRNA-derived fragments as well as mRNA-derived transcripts, during the transition to either mycelia or spherules, which may play roles in cell-cell, and/or host-pathogen communication. Going forward, this newly established intra- and extracellular Coccidioides sRNA atlas will provide a foundation for potential biomarker discovery and contribute to our understanding of the molecular basis for virulence in Valley fever.

molecular biology↗

bioRxiv2022

Small Molecule Inducers of Neuroprotective miR-132 Identified by HTS-HTS in Human iPSC-derived Neurons

MicroRNAs (miRNAs) are short RNAs that regulate fundamental biological processes. miR-132, a key miRNA with established functions in Tau homeostasis and neuroprotection, is consistently downregulated in Alzheimers disease (AD) and other tauopathies. miR-132 overexpression rescues neurodegenerative phenotypes in several AD models. To complement research on miRNA-mimicking oligonucleotides targeting the central nervous system, we developed a high-throughput-screen coupled high-throughput-sequencing (HTS-HTS) in human induced pluripotent stem cell (iPSC)-derived neurons to identify small molecule inducers of miR-132. We discovered that cardiac glycosides, which are canonical sodium-potassium ATPase inhibitors, selectively upregulated miR-132 in the sub-M range. Coordinately, cardiac glycoside treatment downregulated total and phosphorylated Tau in rodent and human neurons and protected against toxicity by glutamate, N-methyl-D-aspartate, rotenone, and A{beta} oligomers. In conclusion, we identified small-molecule drugs that upregulated the neuroprotective miR-132 and ameliorated neurodegenerative phenotypes. Our dataset also represents a comprehensive resource for discovering small molecules that modulate specific miRNAs for therapeutic purposes.

neuroscience↗