bioRxiv Science⌕ Search

bioRxiv · 10.1101/167452

TruePaiR: Software for the Accurate Identification of Complementary piRNA Read Pairs in High-Throughput Sequencing Data

Abstract

piRNAs and their biogenesis pathways are well-conserved in Metazoans (Grimson et al. 2008). piRNAs have been implicated in transcriptional, post-transcriptional, and translational regulation (Grivna et al. 2006; Lin & Yin 2008; Brennecke et al. 2008; Brennecke et al. 2007; Aravin et al. 2007). We analyze the signatures of a critical process in the primary and secondary mechanism of piRNA biogenesis, referred to as the amplification loop.\n\nThe presence of U-1 and A-10 bias within piRNA populations is an indicator, but not an absolute measure of piRNA amplification. By further considering imperfect and perfect sequence complementarity within the first ten base pairs of piRNAs, the active site promoting secondary piRNA biogenesis, we developed practical and statistically powerful metrics to observe relative piRNA amplification. TruePaiR is a fast and effective general software tool to assess the relative utilization of piRNA amplification in high throughput sRNA sequencing data.\n\nThe results of TruePaiR runs in seven species and five tissues serve as a benchmark for meaningful context of piRNA amplification. The TruePaiR metrics provide foundational data regarding the in terms of species specificity, tissue specificity, as well as the relative participation based upon origin-based piRNA subsets regarding piRNA amplification. The low degree of variability of same sample TruePaiR runs allows for metric reliability, reproducibility, as well as the ability to detect subtle differences in piRNA amplification within and between species and tissues. Given that TruePaiR serves as an effective and consistent metric of piRNA amplification across species, it can represent a new, meaningful standard in the degree of piRNA amplification in a specific organism and tissue that is or is not expected to undergo piRNA amplification.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Schreiner, P. A., Atkinson, P. W.. 2017-07-23. TruePaiR: Software for the Accurate Identification of Complementary piRNA Read Pairs in High-Throughput Sequencing Data. https://doi.org/10.1101/167452

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

scRM: A single-cell foundation model trained on scRNA-seq reads

To our knowledge, scRM is the first single-cell foundation model trained on sequencing reads, demonstrating that raw data pretraining is not only feasible but competitive at a fraction of the computational cost. We anticipate that scaling this framework and exploring alternative architectures will unlock biological information inaccessible to count models and extend the dataset-specific pretraining it already makes possible. The source code is available at https://github.com/altos-labs/scRM.

bioinformatics↗

Local fractal dimension as an indicator of functional reorganization in molecular interaction networks

Changes in protein abundance incompletely describe how molecular perturbations reshape cellular organization. Here we introduce DIFFRACT, a framework that integrates quantitative proteomics with protein-protein interaction networks to identify reorganization through changes in local fractal dimension. Molecular associations define effective distances between connected proteins, allowing the geometry of their surrounding network neighborhoods to be compared across conditions. Analyses across four organisms (E. coli, A. thaliana, C. elegans, and H. sapiens) and three interaction resources (STRING, BioGRID, and IntAct) establish heterogeneous local scaling, while controlled perturbations demonstrate sensitivity to regional changes and invariance to uniform distance rescaling. Applied to RAVER1-deficient A549 cells, DIFFRACT identifies components associated with established RNA-regulatory functions and candidate roles in tRNA biology, mitochondrial organization and ciliogenesis. Selected RNA-regulatory and ciliary themes are not significantly enriched by abundance-ranked gene set analysis, supporting complementary information from network geometry. Selected functional annotations also recur in HEK293T cells. Guided by the ciliary predictions, we show that RAVER1 depletion increases the proportion of ciliated A549 cells 2.57-fold and increases cilium length. DIFFRACT thus connects changes in molecular network geometry to experimentally testable biological responses, extending the interpretation of proteomic perturbations beyond differential abundance.

bioinformatics↗

Peripheral Exercise Transcriptomes Do Not Converge on Glutamatergic or Neuroinflammatory Signatures: A Cross-Platform Meta-Analysis

Executive dysfunction following physical overtraining has been linked to glutamatergic dysregulation in the lateral prefrontal cortex (LPFC), but whether this central mechanism is reflected in peripheral gene expression is unknown. This study tested whether peripheral transcriptomic responses to exercise converge on the glutamatergic or neuroinflammatory pathways implicated in LPFC dysfunction. Three publicly available GEO datasets spanning skeletal muscle, whole blood, and circulating neutrophils were analyzed across four exercise groups using limma, with a discovery threshold of nominal p < 0.05 and absolute log2 fold change above 0.5. Differential expression analysis identified 7,311 unique differentially expressed genes (DEGs) across the four contrasts, but overlap between datasets was limited: 7 genes were shared between skeletal muscle and blood, 38 between skeletal muscle and the GSE43856 contrasts, and 90 between blood and the GSE43856 contrasts, with none significant across all three studies. Gene Ontology and KEGG enrichment of the DEG union identified ribonucleoprotein complex biogenesis, ribosome biogenesis, protein folding, and T cell activation as the dominant biological processes; no glutamatergic or neuroinflammatory terms reached significance. Cross-tissue concordance between skeletal muscle and blood was absent (r = 0). Effect sizes among the genes driving the top enriched pathways were dominated by ribosomal proteins, heat shock proteins, and translation initiation factors rather than glutamate receptors or transporters. These findings indicate that peripheral transcriptomic responses to exercise are tissue-specific and dominated by proteostasis, translational, and immune programs rather than glutamatergic signaling. Direct assessment of central nervous system tissue or fluid-based glutamatergic biomarkers may be required to link overtraining-induced fatigue to LPFC dysfunction.

bioinformatics↗