Vera, G. | bioRxiv Science

bioRxiv2024

TOTEM: A web TOol for Tissue-EnrichMent analysis on gene lists

Analysis of spatiotemporal patterns of gene expression is crucial to decode biological systems responses. High-throughput sequencing allows in-depth transcriptome analyses and experimental designs, providing valuable reference expression atlases. Specifically, testing overrepresentations of tissue-specific genes based on these atlases can provide valuable insights; however, such an approach is not accessible to inexperienced users. Here, we introduce TOTEM (TOol for Tissue-EnrichMent), a web tool designed to calculate enrichment values per tissue by identifying tissue-specific genes from an organ/organism of interest given a user gene list. Results are visually represented, and users gene classified. The utility of TOTEM is manifest when using integrated single cell expression atlases, enabling the study of complicated tissues, with the maximum possible resolution. Its effectiveness is validated by the study of BRL3 role in stress specifically from the vascular tissues. Finally, TOTEMs modular design allows for continual integration of new experiments. TOTEM can be freely accessed at: https://totemwebtool.com.

plant biology↗

bioRxiv2020

De novo coding variants in the AGO1 gene cause a neurodevelopmental disorder with intellectual disability

High-impact pathogenic variants in more than 1,000 protein-coding genes cause Mendelian forms of neurodevelopmental disorders (NDD), including the newly reported AGO2 gene. This study describes the molecular and clinical characterization of 28 probands with NDD harboring heterozygous AGO1 coding variants. De novo status was always confirmed when parents were available (26/28). A total of 15 unique variants leading to amino acid changes or deletions were identified: 12 missense variants, two in-frame deletions of one codon, and one canonical splice variant leading to a deletion of two amino acid residues. Some variants were recurrently identified in several unrelated individuals: p.(Phe180del), p.(Leu190Pro), p.(Leu190Arg), p.(Gly199Ser), p.(Val254Ile) and p.(Glu376del). AGO1 encodes the Argonaute 1 protein, which functions in gene-silencing pathways mediated by small non-coding RNAs. Three-dimensional protein structure predictions suggest that these variants might alter the flexibility of the AGO1 linkers domains, which likely would impair its function in mRNA processing. Affected individuals present with intellectual disability of varying severity, as well as speech and motor delay, autistic behavior and additional behavioral manifestations. Our study establishes that de novo coding variants in AGO1 are involved in a novel monogenic form of NDD, highly similar to AGO2 phenotype.

genetics↗