Biology subjects

Tapinos, A.

Publications and source records attributed to Tapinos, A..

4 recordsLinked to original sources

bioRxiv2026

Replication fork directionality reveals how structural variants arise under replication stress

Structural variants (SVs) in cancer are associated with defects in DNA repair and replication stress, but the mechanisms generating common SV types remain unresolved. We propose that large (>100 kb) tandem duplications originate through a novel sister-fork breakage-fusion mechanism. To capture replication-related context beyond breakpoints, we developed an algorithm to characterize replication timing, origin density, and fork direction across SV-spanned regions, features that refine and differentiate previously defined SV signatures. Large tandem duplications frequently overlap replication origins from which forks proceed bidirectionally; combined with independent evidence from APOBEC strand asymmetry, this pattern is compatible uniquely with the proposed mechanism. Although tandem duplications in CCNE1-amplified and CDK12-mutant cancers also concentrate around origins and highly transcribed genes, they display distinct contexts: CDK12-mutant SVs arise near later-firing origins, whereas those in CCNE1-amplified tumors often coincide with genes in specific strand configurations, suggesting different causes of fork stalling. Incorporating replication features into signature analysis enabled the discovery of new SV signatures, which we used to build SVIG, a multi-class classifier of SV phenotypes. SV signatures attributed to replication stress may help guide therapies targeting this vulnerability.

bioinformatics↗

bioRxiv2026

Whole genome sequencing of endometrial cancer identifies novel subgroups, drivers, and actionable alterations

Endometrial cancer (EC) is the most common gynaecological malignancy in high income countries, and is increasing in incidence. While molecular stratification has improved its management, precision care is hampered by incomplete characterization of the EC genome. We address this by analysis of whole genome sequencing (WGS) of 665 ECs generated by the UK Genomics England 100,000 Genome Project (100kGP). 5% of cases were associated with germline pathogenic variants in cancer genes, including BRCA1 which we confirmed predisposes to EC. We identified 107 putative coding driver genes, 35% of which had no prior established role in EC. Novel structural variants included gains of MYCN and loss of its negative regulator NEDD4.1 which were significantly mutually exclusive in copy number (CN) high tumours. Immunogenomic analysis confirmed selection for driver alterations of low immunogenicity based on patient HLA haplotype, and pervasive immune escape through multiple mechanisms. Unsupervised clustering of mutational signatures and genomic alterations identified known and novel molecular subgroups, including a CN-high subset with mutational signatures of homologous recombination deficiency (HRD) and favourable outcome. Independent prognostic value of single nucleotide variant (SNV) burden, CN burden and multiple coding drivers, along with the identification of targetable molecular alterations in over one-third of cases, underscores the promise of WGS for precision medicine in EC.

genomics↗

bioRxiv2020

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

Asthma development and persistence is tightly linked to respiratory viruses. Viral presence is usually interrogated with targeted approaches during periods of disease activity and/or infections, thus neglecting viral occurrence during steady states. We investigate the virome in the upper respiratory system of healthy and asthmatic preschool children during asymptomatic/non-infection periods using metagenomics. Children with asthma have a characteristically dysbiotic virome that correlates to disease severity and control. The major component of dysbiosis is bacteriophage deficiency, while eukaryotic viral presence is increased. At the metacommunity level, differential virus species co-occurrence patterns suggest a decrease of the microbiota community resilience in asthma. Viral dysbiosis is therefore a key characteristic of asthma pathophysiology.

microbiology↗

bioRxiv2016

Metagenomic Binning through Multi-resolution Genomic Binary Patterns

Bioinformatics methods typically use textual representations of genetic information, represented computationally as strings or sub-strings of the characters A, T, G and C. Image processing methods offer a rich source of alternative descriptors as they are designed to work in the presence of noisy data without the need for exact matching. We introduce a method, multi-resolution local binary patterns (MLBP) from image processing to extract local texture changes from nucleotide sequence data. We apply this feature space to the alignment-free binning of metagenomic data. The effectiveness of MLBP is demonstrated using both simulated and real human gut microbial communities. The intuition behind our method is the MLBP feature vectors permit sequence comparisons without the need for explicit pairwise matching. Sequence reads or contigs can then be represented as vectors and their texture compared efficiently using state-of-the-art machine learning algorithms to perform dimensionality reduction to capture eigengenome information and perform clustering (here using RSVD and BH-tSNE). We demonstrate this approach outperforms existing methods based on k-mer frequency. The image processing method, MLBP, thus offers a viable alternative feature space to textual representations of sequence data. The source code for our Multi-resolution Genomic Binary Patterns method can be found at https://github.com/skouchaki/MrGBP.

bioinformatics↗