Biology subjects

Al-Abri, R.

Publications and source records attributed to Al-Abri, R..

3 recordsLinked to original sources

bioRxiv2026

African Green Monkey Cerebrospinal Fluid miRNome Captures Conserved miRNAs Relevant to Human Neurodegenerative Disease

BackgroundThe African green monkey (AGM) is increasingly used as a model for early-stage Alzheimers disease (AD), with cerebrospinal fluid (CSF) targeted for biomarker discovery and longitudinal disease monitoring of shifts in the central nervous system. MicroRNAs (miRNAs) are particularly informative indicators of early neuropathological change. Despite the complementary value of an early-stage disease model and a molecular marker capable of capturing early change, the miRNA composition (miRNome) of AGM remains undefined. We established the AGM CSF miRNome from antemortem samples using miRNA sequencing and a qRT-PCR-based array. We also developed a hierarchical annotation pipeline to classify miRNAs as either family-conserved or unclassified and to assess sequence alignment across humans and other species. ResultsWe used untargeted miRNA sequencing to characterize the AGM CSF miRNome and identified 205 miRNAs that could be classified into three family-conserved categories: canonical, noncanonical, and 3'-terminal variants. Of these, 150 were also detected using a human-targeted qRT-PCR array, providing independent support for the sequence-derived miRNome. Sequencing abundance and qRT-PCR array Ct values showed significant cross-platform concordance overall, although concordance was lower for 3'-terminal isomiRs than for canonical miRNAs. Comparison with human GTEx tissue-expression data indicated that several human homologs of AGM CSF miRNAs exhibited brain-preferential expression. Notably, predicted targets of many of these miRNAs were enriched for pathways implicated in neurodegenerative disease. Finally, we identified 20 unclassified candidates that could not be assigned to established miRNA families, two of which we propose as putatively novel miRNAs. ConclusionThe AGM CSF miRNome is substantially conserved with the human miRNome but also contains 3'-terminal isomiRs and unclassified miRNA candidates. AGM CSF contains miRNAs homologous to human miRNAs associated with AD and other neuropathologies, highlighting the translational potential of this model. However, our study also reveals challenges related to species-specific sequence variation and reduced cross-platform concordance for isomiRs. Thus, comparative studies will be needed to validate the functional and biomarker relevance of these miRNAs across species. More generally, this initial miRNome provides a reference resource for future studies of miRNAs in AGM across disease-related, physiological, experimental, and evolutionary contexts.

genomics↗

bioRxiv2025

ScatTR: Estimating the Size of Long Tandem Repeat Expansions from Short-Reads

Tandem repeats (TRs) are sequences of DNA where two or more base pairs are repeated back-to-back at specific locations in the genome. The expansions of TRs are implicated in over 50 conditions, including Friedreichs ataxia, autism, and cancer. However, accurately measuring the copy number of TRs is challenging, especially when their expansions are larger than the fragment sizes used in standard short-read genome sequencing. Here we introduce ScatTR, a novel computational method that leverages a maximum likelihood framework to estimate the copy number of large TR expansions from short-read sequencing data. ScatTR calculates the likelihood of different alignments between sequencing reads and reference sequences that represent various TR lengths and employs a Monte Carlo technique to find the best match. In simulated data, ScatTR outperforms state-of-the-art methods, particularly for TRs with longer motifs and those with lengths that greatly exceed typical sequencing fragment sizes. When applied to data from the 1000 Genomes Project, ScatTR detected potential large TR expansions that other methods missed, highlighting its ability to better identify genome-wide characterization of TR variation. ScatTR can be accessed via: https://github.com/g2lab/scattr.

bioinformatics↗

bioRxiv2022

A genome-wide atlas of recurrent repeat expansions in human cancer

Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases. However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs (STRs), a phenomenon termed microsatellite instability (MSI); however larger repeat expansions have not been systematically analyzed in cancer. Here, we identified TR expansions in 2,622 cancer genomes, spanning 29 cancer types. In 7 cancer types, we found 160 recurrent repeat expansions (rREs); most of these (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with an enrichment near candidate cis-regulatory elements, suggesting a role in gene regulation. One rRE located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, targeting cells harboring this rRE with a rationally designed, sequence-specific DNA binder led to a dose-dependent decrease in cell proliferation. Overall, our results demonstrate that rREs are an important but unexplored source of genetic variation in human cancers, and we provide a comprehensive catalog for further study.

genomics↗