Biology subjects

Tahir, R.

Publications and source records attributed to Tahir, R..

4 recordsLinked to original sources

bioRxiv2026

CCTP-Atlas: Compartment-Resolved Ciliary Transcriptional Dysregulation in Tetralogy of Fallot, A Six-Dataset Integrative Meta-Analysis

Background. Primary cilia coordinate Hedgehog-dependent outflow tract morphogenesis. Concurrent human genetics implicates ciliary loss-of-function in nonsyndromic tetralogy of Fallot (TOF) risk, yet compartment-resolved ciliary transcriptional programmes in public TOF snRNA-seq remain unmapped at module resolution. Methods. We curated a Cardiac Ciliary Transcriptomic Panel (CCTP; 1,611 genes; four modules) and executed a ten-phase integrative pipeline on six public sc/snRNA-seq resources. Differentially expressed gene tables were harmonised (adjusted p < 0.05; |log2FC| [≥] 0.5 where available), mapped to CCTP modules, and tiered by evidence strength. Patient-level pseudobulk (three TOF versus five donors), permutation-validated Compartment Dysregulation Index (CMDI), Cross-Species Concordance Score (CSCS), STRING protein-protein interaction analysis, and diffusion pseudotime on 17,290 Ho organoid cells were performed. Results. Among 1,263 unique CCTP-associated hits, 396 genes recurred in at least two dataset tables (exploratory tier; Tier A endothelial anchor n = 24 from Zulibiya et al.). Only Zulibiya endothelial M1 structural-assembly CMDI exceeded a module-size-matched permutation null (p = 0.015). Patient-level pseudobulk returned zero false-discovery-rate-significant CCTP genes. CCTP-conditioned overlap with recent ciliary genetics was non-significant (Fisher p {approx} 0.13). Ho organoid pseudotime showed highest M1/M2 activity at day 8, declining toward day 21. Genome-wide CSCS classified 11 genes as fully conserved and 136 as partially conserved among scoreable orthologs. Conclusions. Ciliary transcriptional correlates in TOF are compartment-specific and module-structured, with the strongest inferential signal in TOF endothelium (M1). CCTP-Atlas provides a reproducible, tiered prioritisation resource linking public TOF snRNA-seq, organoid maturation proxies, and partial cross-species patterns. Findings are hypothesis-generating and complement but do not replicate recent ciliary genetics evidence until expanded cohorts and functional validation are performed. Data availability. Processed gene lists, manifests, and scripts. Source datasets: GSE203274, GSE168464, GSE166462, GSE126128; Li et al. (2025) supplementary tables. This is a preprint and has not been peer-reviewed.

bioinformatics↗

bioRxiv2026

WNT8B and -9B promote the survival and dissemination of dormant ovarian cancer cells

Cancer cell dormancy and the resultant resistance to conventional therapies present significant challenges for the successful treatment of high-grade serous ovarian cancer (HGSC). We used genome wide, and specialized sgRNA, libraries in CRISPR-based screens to identify critical cell survival mechanisms in dormancy and metastasis. Our findings demonstrate that low expression Wnt ligands WNT8B and WNT9B are essential for sustaining cell survival during prolonged dormant spheroid culture conditions. These Wnt ligands utilize non-canonical signaling to activate expression of stem cell genes such as ALDH1A1, CD44 and others during spheroid dormancy. The loss of WNT8B and WNT9B reduced survival of xenografted ovarian cancer cells during early dissemination of disease that extended survival. Furthermore, treatment of WNT8B/9B deficient xenografts with carboplatin demonstrated increased sensitivity that further reduced dissemination and extended survival. These findings reveal that rare Wnt ligands can possess outsized functions in cancer pathogenesis and offer new avenues for improving treatment outcomes for HGSC through their inhibition.

cancer biology↗

bioRxiv2024

Investigating the Structural Impact and Conformational Dynamics of a Sequence Variant (c.242G>A) in TMIE Gene Provoking Usher Syndrome

Usher syndrome (USH) is a retinal autosomal recessive genetic disorder, characterized by congenital severe-to-profound sensorineural hearing loss, retinitis pigmentosa (RP), and rarely vestibular dysfunction. A transmembrane inner ear gene TMIE causing autosomal recessive usher syndrome hearing loss, which may open up interesting perspectives into the function of this protein in inner ear. This disease is linked with mutations in TMIE gene. In this study delineates the pathogenic association, miss-fold aggregation, and conformational paradigm of a missense variant (c.242G>A) resulting into (p.Arg81His) in TMIE gene segregating usher syndrome through a molecular dynamics simulations approach. The transmembrane inner ear expressed protein assumes a critical role as its helices actively engage in binding with specific target DNA base pairs. The alteration observed in the mutant protein, characterized by an outward repositioning of the proximal helical portion, which is attributed to the absence of preceding beta-hairpins in the C-terminal region. This structural modification results in the loss of hydrogen bonds, exposure of hydrophobic residues to the solvent, and a consequential transformation of helices into loops, ultimately leading to functional impairment in the TMIE protein. These notable modifications in the stability and conformation of the mutant protein were verified through essential dynamics analysis, revealing that a point mutation induces distinct overall motions and correlations between proteins, ultimately resulting in usher syndrome. The current study provides insilico evidences of Usher syndrome hearing loss disease as protein folding disorder. The energy calculation also revealed that there is a difference of -251.211Kj/mol which also indicates that the SNP has significantly decreased the stability of protein consequently folding into Usher syndrome. This study contributes molecular insights into the structural correlation between the TMIE protein and usher syndrome. The docking analysis highlight various interaction between wild and mutant structure emphasizing key residues involved in hydrogen and hydrophobic interaction.

bioinformatics↗

bioRxiv2021

Proximity-dependent biotinylation to elucidate the interactome of TNK2 non-receptor tyrosine kinase

Non-receptor tyrosine kinases represent an important class of signaling molecules which are involved in driving diverse cellular pathways. Although, the large majority have been well-studied in terms of their protein-binding partners, the interactomes of some of the key non-receptor tyrosine kinases such as TNK2 (also known as activated Cdc42-associated kinase 1 or ACK1) have not been systematically investigated. Aberrant expression and hyperphosphorylation of TNK2 has been implicated in a number of cancers. However, the exact proteins and cellular events that mediate phenotypic changes downstream of TNK2 are unclear. Biological systems that employ proximity-dependent biotinylation methods, such as BioID, are being increasingly used to map protein-protein interactions as they provide increased sensitivity in discovering interaction partners. In this study, we employed BioID coupled to the biotinylation site identification technology (BioSITe) method that we recently developed to perform molecular mapping of intracellular proteins associated with TNK2. We also employed stable isotope labeling with amino acids in cell culture (SILAC) to quantitatively explore the interactome of TNK2. By performing a controlled comparative analysis between full-length TNK2 and its truncated counterpart, we were not only able to confidently identify site-level biotinylation of previously well-established TNK2 binders and substrates such as NCK1, NCK2, CTTN, STAT3, but also discover several novel TNK2 interacting partners. We validated TNK2 interaction with one of the novel TNK2 interacting protein, clathrin interactor 1 (CLINT1), using immunoblot analysis. Overall, this work reveals the power of the BioSITe method coupled to BioID and highlights several molecules that warrant further exploration to assess their functional significance in TNK2-mediated signaling.

cancer biology↗