Biology subjects

Silva, I.

Publications and source records attributed to Silva, I..

18 recordsLinked to original sources

bioRxiv2026

Exploring the relationship between dolphins and fisheries: uncovering the spatial and temporal patterns that influence potential conflicts along Portugal's north coast

The north coast of mainland Portugal supports a strong dolphin presence and extensive fishing activity, increasing the likelihood of interactions, such as bycatch. This study provides an initial assessment of potential conflict areas, using automatic identification system (AIS) data from Global Fishing Watch. To this end, sighting data from the ATLANTIDA project (2021-2024) on the common dolphin (Delphinus delphis) were used to describe spatiotemporal patterns of occurrence and encounter rates, and to predict their association with fishing effort to identify and map areas of potential overlap. A generalised additive model (GAM) was then applied, integrating environmental, spatial, temporal, and fisheries-related variables to identify the main predictors of species occurrence. Common dolphins were frequently observed during the summer, with an average encounter rate of 3.662 sightings/km. This high encounter rate may be associated with factors such as sea surface temperature, diet, and purse seine fishing activity. The maps showed a spatial overlap between fishing grounds and areas of common dolphin occurrence. Fishing effort was nearly identical between locations with sightings (2.00 h/km{superscript 2}) and those without (1.62 h/km{superscript 2}), suggesting that dolphins are not actively avoiding fishing areas but may instead frequent them due to shared habitat preferences. The best-fitted GAM indicated that encounters were related to year, latitude, fishing effort, depth, sea surface temperature, and season. There was an increase in occurrence over the years and a decrease with increasing fishing effort and sea surface temperature, possibly linked to changes in prey availability, although broad confidence intervals warrant cautious interpretation. Despite some limitations encountered in this study, we believe our findings provide valuable insights into the relationship between dolphin occurrence, environmental conditions, and fishing activities in the area, establishing an important baseline for future conservation and fisheries management efforts.

ecology↗

bioRxiv2026

SlytheRINs: using graph parameters and residue interaction networks to analyze protein dynamics and structural ensembles

Establishing the relationship between protein structure and functional behavior remains a significant challenge. The recognition that proteins are inherently dynamic, with functions often dependent on conformational changes, is increasingly accepted. Among computational approaches for elucidating protein properties, Residue Interaction Network (RIN) analysis has emerged as a powerful tool. However, conventional RIN analysis is constrained by its reliance on single, static protein structures, which fail to capture the flexibility inherent in dynamic protein folding transitions. To address these limitations, SlytheRINs is introduced as an interactive tool designed for comparative analysis of protein conformations via RINs. SlytheRINs enables dynamic ensemble analysis by decomposing interaction network data across multiple conformations of a single protein and providing detailed residue-interaction mapping across conformational changes via graph parameters in comparative plots. Applying these principles, the conformational variations of the wild-type and a pathogenic variant (G188R) of the human Glucose-6-Phosphatase (G6PC1) catalytic subunit were compared to identify fluctuations in both chemical interactions and graph features associated with conformational changes induced by the residue modification. The analyses identified key shifts in dynamic residue interactions in the protein variant that compromise substrate binding and the catalytic site, thereby elucidating the impact on G6PC1s dynamic behavior and the resulting activity loss. AvailabilityThe source code for SlytheRINs is available on GitHub (https://github.com/evomol-lab/SlytheRINs), while the web tool and documentation are available at https://slytherins.streamlit.app.

bioinformatics↗

bioRxiv2025

Too few, too many, or just right? Optimizing sample sizes for population-level inferences in animal tracking projects

O_LISuccessful animal tracking projects depend on well-informed sampling strategies and robust methods to yield biologically meaningful inferences. Considering financial and logistical constraints, the reliability of research outputs is shaped by key decisions regarding study duration (how long should each individual be tracked?), sampling frequency (how often should new locations be collected?), and how many individuals should be tracked. To maximize their conservation value, studies must consider estimator precision and avoid biased inferences of key parameters related to movement behavior and space use, as this can lead to wasted resources and misguide management actions. C_LIO_LITo address these challenges, we propose a workflow for determining the optimal sample sizes for population-level home range area and speed estimates, explicitly addressing the trade-offs between sampling duration (T), sampling interval (reciprocal of frequency; {Delta}t), and population sample size (m). While a priori study design is considered best practice, this workflow can be applied at multiple stages, including concurrent with data collection, or as a post hoc evaluation. C_LIO_LIBy selecting robust methods that are sampling-insensitive, and by quantifying and propagating uncertainty through downstream analyses, we can determine whether our sample sizes (both at the individual- and population-level) are sufficient to yield robust population-level inferences. Furthermore, researchers can integrate additional logistical constraints such as fix success rate, location error, and potential device malfunctions, while also accounting for individual variation. We illustrate potential applications of this workflow through empirically-guided simulations. C_LIO_LITo facilitate its use and implementation, we incorporated this workflow into the user-friendly movedesign R Shiny application. This application enables researchers to easily test different sampling strategies, and as of version 0.3.3, integrates population-level analytical targets. This workflow has the potential to improve the rigor and reliability of animal tracking projects conducted under logistical and financial constraints, and thereby support more effective scientific research, wildlife management, and conservation efforts. It can also support grant or permit submissions by generating evidence-based recommendations for the number of biologgers needed or sampling effort required to achieve research objectives. C_LI

ecology↗

bioRxiv2025

Sensing of extracellular ATP via P2RX7 drives lung tumor growth through regulatory T cell suppressive function

Lung cancer is the leading cause of cancer-related deaths worldwide and, despite treatment advances, immune suppression remains an obstacle to effective therapy. Effector CD4+ T cells (CD4+ Teffs) are critical for antitumor immunity, but their function is often inhibited by regulatory T cells (Tregs), which accumulate in lung tumors and perform suppressive functions through multiple mechanisms. This suppression leads to tumor progression and poor patient outcomes. However, the mechanisms underlying Treg-mediated suppression are not fully understood. Here, we identify the extracellular ATP receptor P2RX7 as a key regulator of Treg function in lung tumors. Using a murine lung cancer model induced by Lewis lung carcinoma cells, we demonstrate that P2RX7 enhances the suppressive capacity of tumor-infiltrating Tregs, promoting tumor growth. In T cell-specific P2RX7-KO mice, reduced Treg infiltration was accompanied by increased CD4+ Teff accumulation and improved tumor control. Treg-specific P2RX7-KO mice exhibit reduced tumor growth, confirming a cell-intrinsic role of P2RX7 in Tregs. Suppression assays revealed that tumor-infiltrating WT Tregs have greater suppressive activity compared to P2RX7-KO Tregs, which failed to inhibit type 1 and Tfh-like responses. This was associated with increased tumor-specific IgG production by lung B cells in P2RX7-KO mice. We also observed that WT Tregs express higher levels of the immunosuppressive surface molecule CTLA-4 when compared to P2RX7-KO Tregs. In summary, we show that P2RX7 expression on Tregs is essential for their suppressive function in lung cancer, and targeting of P2RX7 may constitute a novel strategy to improve lung cancer treatment by alleviating Treg-mediated immune suppression.

immunology↗

bioRxiv2024

Inflammatory Monocytes Increase Prior to Detectable HIV-1 Rebound Viremia

The persistence of HIV-1 proviruses in latently infected cells allows viremia to resume upon treatment cessation. To characterize the resulting immune response, we compare plasma proteomics and single-cell transcriptomics of peripheral blood mononuclear cells (PBMCs) before, during, and after detectable plasma viremia. We observe unique transcriptional signatures prior to viral rebound including a significant increase in CD16++ monocytes with increased anti-viral gene expression. Inflammatory proteins were identified in plasma after detectable rebound. Identifying early signals of imminent viral rebound after treatment cessation will aid in the development of strategies to prolong time to viral rebound and cure HIV-1.

immunology↗

bioRxiv2024

A KCNC1 Variant Linked to Rett Syndrome Disrupts ER to Golgi Trafficking of Kv3.1 Channel

Intrinsic neuronal excitability, defined by the balance between input and output signals, is crucial to neural function, and its disruption underlies various neurological diseases. Kv3.1 channels, encoded by KCNC1, are essential for high-frequency action potential firing. Variants in these channels are associated with several subtypes of epilepsy. We report a patient with developmental regression and epilepsy, meeting Rett syndrome criteria, who carries a KCNC1 variant encoding the S474C substitution in Kv3.1 (Kv3.1S474C). Electrophysiological and biochemical assays reveal that Kv3.1S474C reduces channel presence in the plasma membrane and is retained in the endoplasmic reticulum (ER). In murine primary cultures expressing Kv3.1S474C, we observed reduced neuronal firing frequency and exclusion of the channel from the axon initial segment (AIS). Consistently, we found a decreased firing frequency using a conductance-based computational neuronal model. In summary, this study identifies a novel link between a KCNC1 variant and Rett syndrome, highlighting the importance of S474 residue in Kv3.1 channel trafficking and function in neurons. SummaryThis study identifies and characterizes a novel KCNC1 variant associated with classical Rett syndrome. This variant disrupts endoplasmic reticulum (ER) to Golgi trafficking of the Kv3.1 channels, highlighting the variants potential role in altered neuronal excitability and neurodevelopmental disorders.

cell biology↗

bioRxiv2023

Plasmodium falciparum MORC protein modulates gene expression through interaction with heterochromatin

Dynamic control of gene expression is critical for blood stage development of malaria parasites. Here, we used multi-omic analyses to investigate transcriptional regulation by the chromatin-associated microrchidia protein, MORC, during asexual blood stage development of the human malaria parasite Plasmodium falciparum. We show that PfMORC (PF3D7_1468100) interacts with a suite of nuclear proteins, including APETALA2 (AP2) transcription factors (PfAP2-G5, PfAP2-O5, PfAP2-I, PF3D7_0420300, PF3D7_0613800, PF3D7_1107800, and PF3D7_1239200), a DNA helicase DS60 (PF3D7_1227100), and other chromatin remodelers (PfCHD1 and PfEELM2). Transcriptomic analysis of PfMORCHA-glmS knockdown parasites revealed 163 differentially expressed genes belonging to hypervariable multigene families, along with upregulation of genes mostly involved in host cell invasion. In vivo genome-wide chromatin occupancy analysis during both trophozoite and schizont stages of development demonstrates that PfMORC is recruited to repressed, multigene families, including the var genes in subtelomeric chromosomal regions. Collectively, we find that PfMORC is found in chromatin complexes that play a role in the epigenetic control of asexual blood stage transcriptional regulation and chromatin organization.

microbiology↗

bioRxiv2023

movedesign: Shiny R app to evaluate sampling design for animal tracking movement studies

O_LIProjects focused on movement behavior and home range are commonplace, but beyond a focus on choosing appropriate research questions, there are no clear guidelines for such studies. Without these guidelines, designing an animal tracking study to produce reliable estimates of space-use and movement properties (necessary to answer basic movement ecology questions), is often done in an ad hoc manner. C_LIO_LIWe developed movedesign, a user-friendly Shiny application, which can be utilized to investigate the precision of three estimates regularly reported in movement and spatial ecology studies: home range area, speed, and distance traveled. Conceptually similar to statistical power analysis, this application enables users to assess the degree of estimate precision that may be achieved with a given sampling design; i.e., the choices regarding data resolution (sampling interval) and battery life (sampling duration). C_LIO_LILeveraging the ctmm R package, we utilize two methods proven to handle many common biases in animal movement datasets: autocorrelated Kernel Density Estimators (AKDE) and continuous-time speed and distance (CTSD) estimators. Longer sampling durations are required to reliably estimate home range areas via the detection of a sufficient number of home range crossings. In contrast, speed and distance estimation requires a sampling interval short enough to ensure that a statistically significant signature of the animals velocity remains in the data. C_LIO_LIThis application addresses key challenges faced by researchers when designing tracking studies, including the trade-off between long battery life and high resolution of GPS locations collected by the devices, which may result in a compromise between reliably estimating home range or speed and distance. movedesign has broad applications for researchers and decision-makers, supporting them to focus efforts and resources in achieving the optimal sampling design strategy for their research questions, prioritizing the correct deployment decisions for insightful and reliable outputs, while understanding the trade-off associated with these choices. C_LI

ecology↗

bioRxiv2022

Clarifying space use concepts in ecology: range vs. occurrence distributions

Quantifying animal movements is necessary for answering a wide array of research questions in ecology and conservation biology. Consequently, ecologists have made considerable efforts to identify the best way to estimate an animals home range, and many methods of estimating home ranges have arisen over the past half century. Most of these methods fall into two distinct categories of estimators that have only recently been described in statistical detail: those that measure range distributions (methods such as Kernel Density Estimation that quantify the long-run behavior of a movement process that features restricted space use) and those that measure occurrence distributions (methods such as Brownian Bridge Movement Models and the Correlated Random Walk Library that quantify uncertainty in an animal movement path during a specific period of observation). In this paper, we use theory, simulations, and empirical analysis to demonstrate the importance of applying these two classes of space use estimators appropriately and distinctly. Conflating range and occurrence distributions can have serious consequences for ecological inference and conservation practice. For example, in most situations, home-range estimates quantified using occurrence estimators are too small, and this problem is exacerbated by ongoing improvements in tracking technology that enable more frequent and more accurate data on animal movements. We encourage researchers to use range estimators to estimate the area of home ranges and occurrence estimators to answer other questions in movement ecology, such as when and where an animal crosses a linear feature, visits a location of interest, or interacts with other animals. Open Research StatementTracking data on Aepyceros melampus, Beatragus hunteri, Bycanistes bucinator, Cerdocyon thous, Eulemur rufifrons, Glyptemys insculpta, Gyps coprotheres, Madoqua guentheri, Ovis canadensis, Propithecus verreauxi, Sus scrofa, and Ursus arctos are publicly archived in the Dryad repository (Noonan et al. 2018; https://doi.org/10.5061/dryad.v5051j2), as are data from Procapra gutturosa (Fleming et al. 2014a; https://doi.org/10.5061/dryad.45157). Data on Panthera onca were taken from (Morato et al. 2018). Additional data are publicly archived in the Movebank repository under the following identifiers: Canis latrans, 8159699; Canis lupus, 8159399; Chrysocyon brachyurus, 18156143; Felis silvestris, 40386102; Gyps africanus, 2919708; Lepus europaeus, 25727477; Martes pennanti, 2964494; Panthera leo, 220229; Papio cynocephalus, 222027; Syncerus caffer, 1764627; Tapirus terrestris, 443607536; Torgos tracheliotus, 2919708; and Ursus americanus, 8170674.

ecology↗

bioRxiv2022

Somatic hypermutation spectra are independent of the local transcriptional and epigenetic landscape

Somatic hypermutation (SHM) of immunoglobulin variable (V) regions modulates antibody-antigen affinity is initiated by activation-induced cytidine deaminase (AID) on single-stranded DNA (ssDNA). Transcription is essential for SHM and AID target genes harbor activating chromatin marks and RNA polymerase II (Pol II) stalling, leading to the model that these features favor higher rates of mutagenesis. However, whether such relationships exist within V regions is undetermined. Here, we directly compared SHM and nascent transcription across four V regions and 275 non-immunoglobulin SHM targets at single-nucleotide resolution using precision run-on sequencing (PRO-seq). Although locales of Pol II enrichment and zones of Pol II stalling were detected within V regions, their correlation with SHM was not statistically significant. Moreover, SHM was robust against major reductions of activating epigenetic marks and transcription. This data suggests that SHM patterns and spectra are established independently of specific local nascent transcriptional features.

immunology↗

bioRxiv2022

Simultaneous isolation of proximal and distal lung progenitor cells from individual mice using a 3D printed guide reduces proximal cell contamination of distal lung epithelial cell isolations

The respiratory epithelium consists of multiple, functionally distinct cell-types and is maintained by regionally-specific progenitor populations which repair the epithelium following injury. Several in vitro methods exist for studying lung epithelial repair using primary murine lung epithelial cells, but isolation methods are hampered by a lack of surface markers distinguishing epithelial progenitors along the respiratory epithelium. Here, we developed a 3D-printed lobe divider (3DLD) to aid in simultaneous isolation of proximal versus distal lung epithelial progenitors from individual mice which give rise to differentiated epithelia in multiple in vitro assays. In contrast to 3DLD-isolated distal progenitor cells, classic manual tracheal ligation methods followed by lobe removal resulted in co-isolation of rare proximal progenitors with distal cells which altered the transcriptional landscape of distal organoid cultures. Thus, cell isolation with the 3DLD generates reproducible distal versus proximal progenitor populations and minimizes the potential for contaminating populations to confound in vitro assays. HighlightsO_LI3DLD reproducibly separates lung lobes and extrapulmonary airways (bronchi/trachea) C_LIO_LI3DLD cell isolation yields consistent isolation of distal epithelial cells (DECs) C_LIO_LIContamination of proximal cells in classic DEC isolations may alter in vitro results C_LIO_LI3DLD allows for simultaneous isolation of proximal and DECs from single animals C_LI eTOC blurbAlsafadi et al. describes a new method for simultaneous isolation of lung epithelial proximal and distal progenitors using the aid of a 3D printed device (3DLD). Both isolated cell types differentiate in multiple in vitro assays. The 3DLD guide minimized contamination of proximal cells in distal cell isolations whose presence can alter the transcriptional landscape of distal epithelial organoids.

cell biology↗

bioRxiv2021

How do King Cobras move across a major highway? Unintentional wildlife crossing structures may facilitate movement.

O_LIGlobal road networks continue to expand, and the wildlife responses to these landscape-level changes need to be understood to advise long-term management decisions. Roads have high mortality risk to snakes because snakes typically move slowly and can be intentionally targeted by drivers. C_LIO_LIWe investigated how radio-tracked King Cobras (Ophiophagus hannah) traverse a major highway in northeast Thailand, and if reproductive cycles were associated with road hazards. C_LIO_LIWe surveyed a 15.3km stretch of Highway 304 to determine if there were any locations where snakes, and other wildlife, could safely move across the road (e.g., culverts, bridges). We used recurse analysis to detect possible road-crossing events, and used subsets of King Cobra movement data to create dynamic Brownian Bridge Movement Models (dBBMM) in an attempt to show movement pathways association with possible unintentional crossing structures. We further used Integrated Step Selection Functions (ISSF) to assess seasonal differences in avoidance of major roads for adult King Cobras in relation to reproductive state. C_LIO_LIWe discovered 32 unintentional wildlife crossing locations capable of facilitating King Cobra movement across the highway. Our dBBMMs failed to show if underpasses were being used by telemetered individuals; however, the tracking locations pre- and post-crossing provided strong evidence of underpass use. Our ISSF suggested a lower avoidance of roads during the breeding season, though the results were inconclusive. With the high volume of traffic, large size of King Cobras and a 98.8% success rate of crossing the road in our study, we strongly suspect that individuals are using the unintentional crossing structures to safely traverse the road. C_LIO_LIFurther research is needed to determine the extent of wildlife underpass use at our study site and globally, alongside using previously proven fencing to facilitate their use. We propose that more consistent integration of drainage culverts and bridges could help mitigate the impacts of roads on some terrestrial wildlife, particularly in areas where roads fragment forests and wildlife corridors. C_LI

ecology↗

bioRxiv2021

Direct tissue sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients

CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. Mechanistically, we unveiled that homotypic T-T cell interactions through non-cognate HLA-DR:TCR contacts regulate TLR4 expression on T cells. TLR4+ T cells possess a two-pronged pathogenic activity. Upon TCR and ICOS engagement, TLR4+ T cells produce IL-21, a cytokine known to sponsor antibody production. However, direct TLR4+ engagement on T cells, by endogenous ligands in the arthritic joint, reprograms them towards an IL-17 inflammatory profile compatible with tissue damage program. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program. TLR4+ T cells could constitute an attractive cellular target and predictive biomarker for erosive arthritis.

immunology↗

bioRxiv2020

Lots of movement, little progress: A review of reptile home range literature

Reptiles are the most species-rich vertebrate group with a broad diversity of life history traits. Biotelemetry is an essential methodology for reptiles as it compensates for several limitations when studying their natural history. We evaluated trends in reptile spatial ecology studies focusing upon quantifying home ranges for the past twenty years. We assessed 290 English-language reptile home range studies published from 2000-2019 via a structured literature review investigating publications study location, taxonomic group, methodology, reporting, and analytical techniques. Substantial biases remain in both location and taxonomic groups in the literature, with nearly half of all studies (45%) originating from the USA. Snakes were most often studied, and crocodiles were least often studied, while testudines tended to have the greatest within study sample sizes. More than half of all studies lacked critical methodological details, limiting the number of studies for inclusion in future meta-analyses (55% of studies lacked information on individual tracking durations, and 51% lacked sufficient information on the number of times researchers recorded positions). Studies continue to rely on outdated methods to quantify space-use (including Minimum Convex Polygons and Kernel Density Estimators), often failing to report subtleties on decisions that have substantial impact on home range area estimates. Moving forward researchers can select a suite of appropriate analytical techniques tailored to their research question (dynamic Brownian Bridge Movement Models for within sample interpolation, and autocorrelated Kernel Density Estimators for beyond sample extrapolation). Only 1.4% of all evaluated studies linked to available and usable telemetry data, further hindering scientific consensus. We ultimately implore herpetologists to adopt transparent reporting practices and make liberal use of open data platforms to maximize progress in the field of reptile spatial ecology.

scientific communication and education↗

bioRxiv2020

No room to roam: King Cobras reduce movement in agriculture

Studying animal movement provides insights into how animals react to land-use changes, specifically how animals can change their behaviour in agricultural areas. Recent reviews show a tendency for species to reduce movements in response to increased human landscape modification, but the study of movement has not been extensively explored in reptiles. We examined movements of a large reptilian predator, the King Cobra (Ophiophagus hannah), in Northeast Thailand. We used a consistent regime of radio-telemetry tracking to document movements across protected forest and adjacent agricultural areas. We then adapted GPS-targeting analytic methods to examine the movement using metrics of site reuse and dynamic Brownian Bridge Movement Model derived motion variance. Examination of motion variance demonstrated that King Cobra movements increased in forested areas and tended to decrease in agricultural areas. Our Integrated Step-Selection Functions indicated that when moving in agricultural areas King Cobras restricted their movements, thereby remaining within vegetated semi-natural areas, often located along the banks of irrigation canals. Site reuse metrics of residency time and number of revisits remained unaffected by distance to landscape features. Neither motion variance nor reuse metrics were consistently affected by the presence of threatening landscape features (e.g. roads, human settlements); suggesting that King Cobras will remain in close proximity to threats, provided habitat patches are available. Although King Cobras displayed heterogeneity in their response to agricultural landscapes, the overall trend suggested a reduction in movements when faced with fragmented habitat patches embedded in an otherwise inhospitable land-use matrix. Reductions in movements are consistent with findings for mammals and forest specialist species.

ecology↗

bioRxiv2020

Revisiting reptile home ranges: moving beyond traditional estimators with dynamic Brownian Bridge Movement Models

Animal movement, expressed through home ranges, can offer insights into spatial and habitat requirements. However, home range estimation methods vary, directly impacting conclusions. Recent technological advances in animal tracking (GPS and satellite tags), have enabled new methods for home range estimation, but so far have primarily targeted mammal and avian movement patterns. Most reptile home range studies only make use of two older estimation methods: Minimum Convex Polygons (MCP) and Kernel Density Estimators (KDE), particularly with the Least Squares Cross Validation (LSCV) and reference (href) bandwidth selection algorithms. The unique characteristics of reptile movement patterns (e.g. low movement frequency, long stop-over periods), prompt an investigation into whether newer movement-based methods -such as dynamic Brownian Bridge Movement Models (dBBMMs)- are applicable to Very High Frequency (VHF) radio-telemetry tracking data. To assess home range estimation methods for reptile telemetry data, we simulated animal movement data for three archetypical reptile species: a highly mobile active hunter, an ambush predator with long-distance moves and long-term sheltering periods, and an ambush predator with short-distance moves and short-term sheltering periods. We compared traditionally used home range estimators, MCP and KDE, with dBBMMs, across eight feasible VHF field sampling regimes for reptiles, varying from one data point every four daylight hours, to once per month. Although originally designed for GPS tracking studies, we found that dBBMMs outperformed MCPs and KDE href across all tracking regimes, with only KDE LSCV performing comparably at some higher-frequency sampling regimes. The performance of the LSCV algorithm significantly declined with lower-tracking-frequency regimes, whereas dBBMMs error rates remained more stable. We recommend dBBMMs as a viable alternative to MCP and KDE methods for reptile VHF telemetry data: it works under contemporary tracking protocols and provides more stable estimates, improving comparisons across regimes, individuals and species.

ecology↗

bioRxiv2018

APOBEC-mediated DNA alterations: a possible new mechanism of carcinogenesis in EBV-positive gastric cancer

Mechanisms of viral oncogenesis are diverse and include the off-target activity of enzymes expressed by the infected cells, which evolved to target viral genomes for controlling their infection. Among these enzymes, the single-strand DNA editing capability of APOBECs represent a well-conserved viral infection response that can also cause untoward mutations in host DNA. Here we show, after evaluating somatic single-nucleotide variations and transcriptome data in 240 gastric cancer samples, a positive correlation between APOBEC3s mRNA-expression and the APOBEC-mutation signature, both increased in EBV+ tumors. The correlation was reinforced by the observation of APOBEC-mutations preferentially occuring in transcriptionally-active loci. The EBV-infection and APOBEC3 mutation-signature axis was confirmed in a validation cohort of 112 gastric cancer patients. Our findings suggest that APOBEC3 upregulation in EBV+ cancer may boost the mutation load, providing further clues to the mechanisms of EBV-induced gastric carcinogenesis. After further validation, this EBV-APOBEC axis may prove to be a secondary driving force in the mutational evolution of EBV+ gastric tumors, whose consequences in terms of prognosis and treatment implications should be vetted.

cancer biology↗

bioRxiv2017

bcGST - an interactive bias-correction method to identify over-represented gene-sets in boutique arrays

Motivation: Gene annotation and pathway databases such as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes are important tools in Gene Set Test (GST) that describe gene biological functions and associated pathways. GST aims to establish an association relationship between a gene set of interest and an annotation. Importantly, GST tests for over-representation of genes in an annotation term. One implicit assumption of GST is that the gene expression platform captures the complete or a very large proportion of the genome. However, this assumption is neither satisfied for the increasingly popular boutique array nor the custom designed gene expression profiling platform. Specifically, conventional GST is no longer appropriate due to the gene set selection bias induced during the construction of these platforms.\n\nResults: We propose bcGST, a bias-corrected Gene Set Test by introducing bias correction terms in the contingency table needed for calculating the Fishers Exact Test (FET). The adjustment method works by estimating the proportion of genes captured on the array with respect to the genome in order to assist filtration of annotation terms that would otherwise be falsely included or excluded. We illustrate the practicality of bcGST and its stability through multiple differential gene expression analyses in melanoma and TCGA cancer studies.\n\nAvailability: The bcGST method is made available as a Shiny web application at http://shiny.maths.usyd.edu.au/bcGST/\n\nContact: kevin.wang@sydney.edu.au

bioinformatics↗