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Biology subjects

Reddin, I. G.

Publications and source records attributed to Reddin, I. G..

4 recordsLinked to original sources

Endometrial transcriptomic and ciliation analysis after scratch shows no signature linked to live birth following IVF

ObjectiveTo determine whether endometrial scratch induces differences in transcriptomic profiles or epithelial cell ciliation in the endometrium at the window of implantation that associate with live birth following IVF. DesignSecondary analysis of 50 matched endometrial biopsies collected within a randomised controlled trial evaluating the clinical effectiveness of endometrial scratch before first-time IVF. SettingEndometrial biopsy samples were obtained from women attending the Jessop Wing of Sheffield Teaching Hospitals. Population or SampleWomen undergoing first-time IVF who received an endometrial scratch in the preceding cycle at the window of implantation (6-10 days after LH surge). MethodsEndometrial biopsies were molecularly dated using transcriptomic menstrual-cycle staging algorithms. Bulk RNA sequencing was analysed using DESeq2 with FDR correction, and principal component analysis (PCA) assessed clustering patterns. Epithelial cell ciliation was quantified using immunohistochemistry and an automated Python-based image analysis pipeline. Main Outcome MeasuresDifferential endometrial gene expression between women with and without live birth after IVF; percentage coverage of ciliated epithelial cells in luminal and glandular regions. ResultsTranscriptomic dating confirmed no differences in menstrual-cycle timing between live-birth and no-live-birth groups. No significant differential gene expression was detected (log2FC >2, FDR <0.05), and PCA showed no clustering by pregnancy outcome. Ciliation coverage did not differ between outcome groups or between glandular and luminal surfaces. ConclusionsWhen implantation timing is precisely defined, endometrial scratch does not produce detectable transcriptomic changes or alterations in epithelial ciliation that distinguish women who achieve live birth after IVF. FundingWellbeing of Women RG2147; Wessex Medical Research; Rosetrees Trust (PGS23/100171).

physiology↗

SMART: A Somatic Mutation Annotation and Reporting Tool for cancer genomics

MotivationTranslational interpretation of somatic variants from targeted oncology panels is hampered by inconsistent transcript prioritisation and by the need for reproducible pipelines that natively integrate OncoKB-derived evidence for research purposes. ResultsWe present SMART (Somatic Mutation Annotation and Reporting Tool), a Dockerised pipeline that embeds OncoKB API-derived annotations, including therapeutic (L1-4), resistance (R1-R3), diagnostic (Dx1-3), prognostic (Px1-3) and FDA levels, directly into a VCF-based workflow. SMART combines this with VEP, CIViC, Cancer Hotspots, ClinVar, SpliceAI, REVEL, LOEUF and gnomAD, applies a unified three-tier transcript prioritisation (whitelist > MANE Select > VEP fallback), and produces three-tiered outputs for computational, bioinformatic and research interpretation. Validation against reference APIs showed full concordance across 804 field-level checks. Availability and ImplementationSource code and Docker image are freely available at https://github.com/WeTGI-colab/SMART under the MIT License. SMART is provided for research use only; use of SMART outputs for patient specific clinical reports, clinical decision-making, or other patient-facing purposes requires appropriate governance and all required third-party licensing, including any OncoKB licence required for patient report generation.

bioinformatics↗

Evidence for independent retroviral syncytin-like Env endogenization in non-placental chondrichthyans

Viviparity and placentation are remarkable examples of convergent evolution across vertebrates. The evolution of the uniquely intimate mammalian placenta has been associated with the repeated independent capture of fusogenic retroviral Env proteins, called syncytins. Research into syncytin capture has therefore been predominantly focused on resolving their central role in mammalian placentation. As such, the presence of syncytin-like Env proteins outside of mammals, and their role in non-placental physiological contexts, remain much less understood. We expanded this understanding by systematically surveying genomes from 36 chondrichthyan species (sharks, rays, skates, and chimaeras), which display a wide range of independently evolved placental and non-placental reproductive strategies, for the presence of syncytin-like Env genes. We identified 295 candidate syncytin-like Env proteins from 16 chondrichthyan species, with a subset displaying conserved fusogenic domains, structural homology with known syncytins, and genomic signatures of endogenization. Using transcriptomic data from the model catshark Scyliorhinus canicula, we found that syncytin-like Env genes are transcriptionally active in diverse adult tissue types. Using two closely related species of Squalus (spiny dogfish), we present evidence that endogenized Env genes are syntenically conserved, indicative of vertical transmission from a common ancestor before species divergence. Notably, we detected no candidates in any placental shark genome, suggesting that syncytin-like Env capture is not a feature of shark placentation. Our findings expand the known phylogenetic breadth and functional scope of syncytin-like Env protein endogenization beyond mammalian placentation, providing a solid foundation for future investigations into the wider role of retroviral capture in vertebrate biology and evolution.

evolutionary biology↗

Changes in the cellular composition of the endometrium during the implantation window are associated with recurrent pregnancy loss

Recurrent pregnancy loss (RPL) affects 1-2% of women trying to conceive, yet in many cases the causes remain unclear. Endometrial function is central to the establishment and maintenance of pregnancy, and endometrial dysfunction may underlie RPL. A greater understanding of the endometrial cell populations and their interactions in women with and without RPL may identify markers of endometrial receptivity and the likelihood of pregnancy success. Single cell RNA sequencing was performed on RPL (n = 3) and control (n = 4) endometrial biopsies collected at days 21-24 of the menstrual cycle, the window of implantation. 10,022 cells were clustered and nine major individual cell types were characterised. Further analysis identified six distinct endometrial stromal cell (EnSCs) and three natural killer (NK) cell sub-populations. In RPL, there were changes in the abundance of specific endometrial stromal and NK cell subpopulations with associated differences in cellular communication between the cell types related to the Wnt pathway and angiogenesis. This is consistent with NK cell signalling orchestrating the difference in abundance of stromal cells and regulating processes needed for successful implantation. These changes in RPL endometrium provide further evidence for an endometrial cause of RPL and identify specific mechanisms for future study.

genomics↗