Biology subjects

Ellison, C.

Publications and source records attributed to Ellison, C..

7 recordsLinked to original sources

bioRxiv2026

PathPinpointR: Predicting the progression of sc-RNAseq samples through reference trajectories.

Single-cell RNA sequencing (scRNA-seq) has transformed our ability to analyse cellular heterogeneity, enabling detailed mapping of cellular progression. Trajectory inference tools construct trajectories from scRNA-seq data, facilitating the tracing of cellular progression through developmental pathways. PathPinpointR (PPR) is a lightweight and user-friendly R package developed to predict and compare the positions of scRNA-seq samples along reference biological trajectories, such as those created from large cell atlas projects. PPR utilises sets of switching-gene events from reference trajectories as indicators of cellular progression. By applying these positional indicators to query datasets, each cell can be accurately assigned a pseudo-time value, providing predictive insight into its position along a trajectory. This information can be used to stage cells within an established developmental process, or to evaluate how different patient samples compare when mapped onto reference disease or drug response trajectories. AvailabilityPathPinpointR is available at https://github.com/moi-taiga/PathPinpointR. Contacto.j.l.rackham@soton.ac.uk

bioinformatics↗

bioRxiv2025

Convergence and conflict among telomere specialized transposons across 60 million years of Drosophilid evolution

The Drosophila telomere is one of the best-studied examples of active transposable elements (TEs) benefitting, rather than harming, a host genome. All Drosophila species lack telomerase and instead have telomeres composed of head-to-tail arrays of specialized retrotransposons. These TEs ostensibly act as mutualists by elongating chromosome ends, but evidence from species closely related to Drosophila melanogaster suggests that telomeric transposons may also antagonize their host genome. Importantly, the limited number of Drosophila species characterized thus far has precluded our ability to delineate idiosyncratic from universal evolutionary forces and genetic mechanisms that shape the history of these TEs. Here, we have surveyed long-read genome assemblies of over 100 species of Drosophila, identifying a total of 396 telomeric TE families. Our findings show that these telomere-specialized elements evolve rapidly and also undergo striking convergent evolution: the complete loss of telomeric TEs has occurred repeatedly across the genus while individual telomeric TE lineages have repeatedly lost one of their two protein-coding genes. These elements have also repeatedly undergone horizontal transfer between distantly related Drosophila lineages and have repeatedly captured host gene fragments that promote their selfish suppression of host TE-silencing systems. Furthermore, telomere specialization itself appears to have evolved convergently, as some non-telomeric families have gained the ability to target their insertions to telomeres. These results provide unprecedented resolution into the evolution of these unusual TEs and highlight several novel mechanisms by which they evolve in conflict both with each other and their host genome despite the essential telomere function they provide.

genomics↗

bioRxiv2021

Transposon Extermination Reveals Their Adaptive Fitness Contribution

Transposable Elements are molecular parasites that persist in their host genome by generating new copies to outpace natural selection. Here we measure the parameters governing the copy number dynamics of the fission yeast Tf2 retrotransposons, using experimental and natural populations and a strain where all Tf2 copies are removed. Natural population genomes display active and persistent Tf2 colonies, but in the absence of selection mitotic recombination deletes Tf2 elements at rates that far exceed transposition. We show that Tf2 elements provide a fitness contribution to their host by dynamically rewiring the transcriptional response to metabolic stress. Therefore, Tf2 elements exhibit a mutualistic rather than parasitic behavior toward their host.

genomics↗

bioRxiv2020

The Drosophila TART transposon manipulates the piRNA pathway as a counter-defense strategy to limit host silencing

Co-evolution between transposable elements (TEs) and their hosts can be antagonistic, where TEs evolve to avoid silencing and the host responds by reestablishing TE suppression, or mutualistic, where TEs are co-opted to benefit their host. The TART-A TE functions as an important component of Drosophila telomeres, but has also reportedly inserted into the D. melanogaster nuclear export factor gene nxf2. We find that, rather than inserting into nxf2, TART-A has actually captured a portion of nxf2 sequence. We show that Nxf2 is involved in suppressing TART-A activity via the piRNA pathway and that TART-A produces abundant piRNAs, some of which are antisense to the nxf2 transcript. We propose that capturing nxf2 sequence allowed TART-A to target the nxf2 gene for piRNA-mediated repression and that these two elements are engaged in antagonistic co-evolution despite the fact that TART-A is serving a critical role for its host genome.

genomics↗

bioRxiv2018

Contingency in the convergent evolution of a regulatory network: Dosage compensation in Drosophila

The repeatability or predictability of evolution is a central question in evolutionary biology, and most often addressed in experimental evolution studies. Here, we infer how genetically heterogeneous natural systems acquire the same molecular changes, to address how genomic background affects adaptation in natural populations. In particular, we take advantage of independently formed neo-sex chromosomes in Drosophila species that have evolved dosage compensation by co-opting the dosage compensation (MSL) complex, to study the mutational paths that have led to the acquisition of 100s of novel binding sites for the MSL complex in different species. This complex recognizes a conserved 21-bp GA-rich sequence motif that is enriched on the X chromosome, and newly formed X chromosomes recruit the MSL complex by de novo acquisition of this binding motif. We identify recently formed sex chromosomes in the Drosophila repleta and robusta species groups by genome sequencing, and generate genomic occupancy maps of the MSL complex to infer the location of novel binding sites. We find that diverse mutational paths were utilized in each species to evolve 100s of de novo binding motifs along the neo-X, including expansions of microsatellites and transposable element insertions. However, the propensity to utilize a particular mutational path differs between independently formed X chromosomes, and appears to be contingent on genomic properties of that species, such as simple repeat or transposable element density. This establishes the \"genomic environment\" as an important determinant in predicting the outcome of evolutionary adaptations.

evolutionary biology↗

bioRxiv2018

Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA

Pancreatic cancers are typically diagnosed at late stage where disease prognosis is poor as exemplified by a 5-year survival rate of 8.2%. Earlier diagnosis would be beneficial by enabling surgical resection or earlier application of therapeutic regimens. We investigated the detection of pancreatic ductal adenocarcinoma (PDAC) in a non-invasive manner by interrogating changes in 5-hydroxymethylation cytosine status (5hmC) of circulating cell free DNA in the plasma of a PDAC cohort (n=51) in comparison with a non-cancer cohort (n=41). We found that 5hmC sites are enriched in a disease and stage specific manner in exons, 3UTRs and transcription termination sites. Our data show that 5hmC density is reduced in promoters and histone H3K4me3-associated sites with progressive disease suggesting increased transcriptional activity. 5hmC density is differentially represented in thousands of genes, and a stringently filtered set of the most significant genes points to biology related to pancreas (GATA4, GATA6, PROX1, ONECUT1) and/or cancer development (YAP1, TEAD1, PROX1, ONECUT1, ONECUT2, IGF1 and IGF2). Regularized regression models were built using 5hmC densities in statistically filtered genes or a comprehensive set of highly variable 5hmC counts in genes and performed with an AUC = 0.94-0.96 on training data. We were able to test the ability to classify PDAC and non-cancer samples with the Elastic net and Lasso models on two external pancreatic cancer 5hmC data sets and found validation performance to be AUC = 0.74-0.97. The findings suggest that 5hmC changes enable classification of PDAC patients with high fidelity and are worthy of further investigation on larger cohorts of patient samples.

cancer biology↗

bioRxiv2018

Rampant cryptic sex chromosome drive in Drosophila

Theory predicts that selfish genetic elements that increase their transmission are prone to originate on sex chromosomes but create strong selective pressure to evolve suppressors due to reduced fertility and distorted population sex ratios. Here we show that recurrent genetic conflict over sex chromosome transmission appears to be an important evolutionary force that has shaped gene content evolution of sex chromosomes in Drosophila. We demonstrate that convergent acquisition and amplification of spermatid expressed gene families are common on Drosophila sex chromosomes, and especially on recently formed ones, and harbor characteristics typical of meiotic drivers. We carefully characterize one putative novel cryptic sex chromosome distortion system that arose independently several times in members of the Drosophila obscura group. Co-amplification of the S-Lap1/GAPsec gene pair on both the X and the Y chromosome occurred independently several times in members of the D. obscura group, where this normally autosomal gene pair is sex-linked due to a sex chromosome - autosome fusion. Investigation of gene expression and short RNA profiles at the S-Lap1/GAPsec system suggest that meiotic drive and suppression likely involves RNAi mechanisms. Our finding suggests that recurrent conflict over sex chromosome transmission has shaped widespread genomic and evolutionary patterns, including the epigenetic regulation of sex chromosomes, the distribution of sex-biased genes, and the evolution of hybrid sterility.

genomics↗