Biology subjects

Onar-Thomas, A.

Publications and source records attributed to Onar-Thomas, A..

3 recordsLinked to original sources

bioRxiv2026

hTERT Expression, Regulation, and Prognostic Significance in Pediatric Medulloblastoma

BackgroundTelomerase reactivation, a hallmark of many cancers, is associated with expression of its catalytic subunit, hTERT. However, the prognostic significance of telomere maintenance mechanisms in pediatric medulloblastoma remains poorly defined. MethodsIn this multi-institutional retrospective study of telomerase expression and hTERT regulation in newly diagnosed children with medulloblastoma, hTERT and MYC expression were assessed by qRT-PCR, normalized to non-neoplastic brain control samples. hTERT promoter methylation was analyzed using quantitative pyrosequencing and Illumina 450k methylation array. Cox proportional-hazard regression analyses evaluated the association of hTERT expression with progression-free survival (PFS) or overall survival (OS). Spearman correlation and Kruskal-Wallis tests correlated hTERT promoter methylation and expression and assessed variations among medulloblastoma subgroups, respectively. ResultsAmong 74 patients with available hTERT expression and outcome data, higher expression was associated with worse OS (HR=1.22, 95% CI: 1.01-1.47, p=0.036) and PFS (HR=1.17, 95% CI: 1.00-1.37, p=0.051) after adjusting for subgroup. Similar results were obtained when adjusting for metastatic status. Group 3 patients had the highest hTERT expression (p=0.001). Pyrosequencing data were available for 61 patients and 450k methylation array data for 292 patients. hTERT promoter was differentially methylated across subgroups with WNT followed by group 3 demonstrating the highest methylation on 450k (p<0.0001), findings that were confirmed by pyrosequencing. hTERT promoter methylation positively correlated with hTERT expression (Spearman correlation=0.42, p=0.02 by 450k and 0.34, p=0.007 by pyrosequencing). No significant correlation was observed between hTERT and MYC expression. ConclusionElevated hTERT expression is associated with worse PFS and OS in medulloblastoma across subgroups, supporting telomerase inhibition as a potential therapeutic strategy.

cancer biology↗

bioRxiv2025

High-resolution digital dissociation of brain tumors with deep multimodal autoencoder

In single cell biology, the complexity of tissues may hinder lineage cell mapping or tumor microenvi-ronment decomposition, requiring digital dissociation of bulk tissues. Many deconvolution methods focus on transcriptomic assay, not easily applicable to other omics due to ambiguous cell markers and reference-to-target difference. Here, we present MODE, a multimodal autoencoder pipeline linking multi-dimensional features to jointly predict personalized multi-omic profiles and cellular compositions, using pseudo-bulk data constructed by internal non-transcriptomic reference and external scRNA-seq data. MODE was evaluated through rigorous simulation experiments and real multiomic data from multiple tissue types, outperforming nine deconvolution pipelines with superior generalizability and fidelity.

bioinformatics↗

bioRxiv2024

High-Dimensional Mediation Analysis with Network Mediators: Applications to Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with survivors frequently experiencing long-term neurocognitive morbidities. Here, we utilize the TOTXVI clinical trial data to elucidate the mechanisms underlying treatment-related neurocognitive side effects in pediatric ALL patients by incorporating brain connectivity network data. To enable such analysis, we propose a high-dimensional mediation analysis method with a novel network mediation structural shrinkage (NMSS) prior, which is particularly suited for analyzing high-dimensional brain structural connectivity network data that serve as mediators. Our method is capable of addressing the structural dependencies of brain connectivity networks including sparsity, effective degrees of nodes, and modularity, yielding accurate estimates of the high-dimensional coefficients and mediation effects. We demonstrate the effectiveness and superiority of the proposed NMSS method through simulation studies and apply it to the TOTXVI data, revealing significant mediation effects of brain connectivity on visual processing speed directed by IT intensity. The findings shed light on the potential of targeted interventions to mitigate neurocognitive deficits in pediatric ALL survivors.

cancer biology↗