Biology subjects

Coope, R.

Publications and source records attributed to Coope, R..

4 recordsLinked to original sources

bioRxiv2026

Allele-specific chromatin modifications of HPV-associated extrachromosomal DNAs in cervical cancer

Cervical cancer, a human papillomavirus (HPV) driven malignancy, is the fourth deadliest cancer in females. Approximately 25% of primary cervical cancers contain circular structures called extrachromosomal DNAs (ecDNAs), which can be entirely composed of human DNA (human-only ecDNAs) or a combination of HPV and human DNA sequences (HPV-human hybrid ecDNAs). Human-only ecDNAs harbour cancer-driving oncogenes, but epigenetic differences between human-only and HPV-human hybrid ecDNAs are unexplored. Here we report that 30% of cervical cancers contained at least one ecDNA. HPV-human hybrid ecDNAs contained more active enhancers and promoters than human-only ecDNAs and invariably contained the HPV oncogenes E6 and E7. These ecDNAs also contained an allelic hypomethylation region associated with putative human promoters, as well as enrichments for motifs associated with recombination hotspots. By leveraging long-read WGS phasing data to separate ChIP-seq data into alleles, we revealed allele-specific peaks in enhancers and promoters on ecDNAs, of which HPV-human hybrid ecDNAs contained a higher density. Overall, we found HPV-human hybrid and human-only ecDNAs differed in their regulation, often at an allele-specific level. Our study more firmly establishes the importance of epigenome disruption in cervical cancer and how structural variation, particularly surrounding HPV integration sites, may shape the surrounding regulatory architecture.

genomics↗

bioRxiv2025

SPIN: Inkjet-Driven Nanowell Workflow for Scalable and Sensitive Single-Cell Proteomics

Single-cell proteomics is emerging as a powerful approach to resolve cellular heterogeneity, yet sample processing remains challenging due to limited input material and the absence of protein amplification. We present a protocol centered on an image-guided, machine-learning-driven inkjet single-cell printer integrated with a dew-point-controlled nanowell chip to reduce loss, increase throughput, and improve reproducibility. The system dispenses single cells at >1 Hz into sealed nanoliter wells with minimal surface contact, virtually eliminating evaporation; a high-thermal-conductivity aluminum substrate and precise environmental control further ensure exceptional reproducibility. Relative to a commercial dispenser, the workflow yields significantly higher protein and peptide recovery without bias toward high-abundance species, delivering uniformly deep coverage. Biological pathway analysis emphasizes the robustness of this workflow, as there is a near 100% protein completeness detected among the enzymes in the Kreb cycle in both A549 and astrocytes, suggesting the consistency across all samples evaluated. This platform addresses core processing bottlenecks and enables reliable, scalable single-cell proteomics.

systems biology↗

bioRxiv2019

Loss of CIC promotes mitotic dysregulation and chromosome segregation defects

CIC encodes a transcriptional repressor and MAPK signalling effector that is inactivated by loss-of-function mutations in several cancer types, consistent with a role as a tumour suppressor. Here, we used bioinformatic, genomic, and proteomic approaches to investigate CICs interaction networks. We observed both previously identified and novel candidate interactions between CIC and SWI/SNF complex members, and also observed novel interactions between CIC and cell cycle regulators and RNA processing factors. We found that CIC loss is associated with an increased frequency of mitotic defects in human cell lines and an in vivo mouse model and with dysregulated expression of mitotic regulators. We also observed aberrant splicing in CIC-deficient cell lines predominantly at 3 and 5 untranslated regions of genes, including genes involved in MAPK signalling, DNA repair, and cell cycle regulation. Our study thus characterises the complexity of CICs functional network and describes the effect of its loss on cell cycle regulation, mitotic integrity, and transcriptional splicing, thereby expanding our understanding of CICs potential roles in cancers. In addition, our work exemplifies how multi-omic, network-based analyses can be used to uncover novel insights into the interconnected functions of pleiotropic genes/proteins across cellular contexts. Simple summaryCapicua (CIC) is a gene that is frequently mutated in several cancer types, including stomach cancers and certain subtypes of brain tumours and sarcomas. CIC, the protein encoded by the CIC gene, has been shown to play a multitude of roles in both normal and cancer cell functions; however, most studies exploring these roles focus on a single aspect of CIC function and may therefore overlook complex interconnected activities in which CIC is involved. In this study, we have used multiple complementary approaches to obtain a broader view of CICs complex functional networks. We observed novel interactions (genetic or physical) between CIC and genes/proteins involved in various aspects of cellular function, including regulation of cell division and processing of RNA molecules. Altogether, our work characterises the complexity of CICs functional network and expands our understanding of its potential roles in cancer.

cancer biology↗

bioRxiv2017

It’s okay to be green: Draft genome of the North American Bullfrog (Rana [Lithobates] catesbeiana)

Frogs play important ecological roles as sentinels, insect control and food sources. Several species are important model organisms for scientific research to study embryogenesis, development, immune function, and endocrine signaling. The globally-distributed Ranidae (true frogs) are the largest frog family, and have substantial evolutionary distance from the model laboratory Xenopus frog species. Consequently, the extensive Xenopus genomic resources are of limited utility for Ranids and related frog species. More widely applicable amphibian genomic data is urgently needed as more than two-thirds of known species are currently threatened or are undergoing population declines.\n\nHerein, we report on the first genome sequence of a Ranid species, an adult male North American bullfrog (Rana [Lithobates] catesbeiana). We assembled high-depth Illumina reads (66-fold coverage), into a 5.8 Gbp (NG50 = 57.7 kbp) draft genome using ABySS v1.9.0. The assembly was scaffolded with LINKS and RAILS using pseudo-long-reads from targeted denovo assembler Kollector and Illumina Synthetic Long-Reads, as well as reads from long fragment (MPET) libraries. We predicted over 22,000 protein-coding genes using the MAKER2 pipeline and identified the genomic loci of 6,227 candidate long noncoding RNAs (IncRNAs) from a composite reference bullfrog transcriptome. Mitochondrial sequence analysis supported Lithobates as a subgenus of Rana. RNA-Seq experiments identified ~6,000 thyroid hormone- responsive transcripts in the back skin of premetamorphic tadpoles; the majority of which regulate DNA/RNA processing. Moreover, 1/6th of differentially-expressed transcripts were putative lncRNAs. Our draft bullfrog genome will serve as a useful resource for the amphibian research community.

genomics↗