Biology subjects

Edwards, D.

Publications and source records attributed to Edwards, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Unsupervised Clustering Enables Cohort-Specific Variant Recalibration in Crops

Genomic selection (GS) and trait discovery in crops require reliable marker datasets, yet variant discovery remains constrained by the lack of standardised, high-confidence reference resources. Publicly available plant genomic resources are often based on outdated reference genomes, heterogenous pipelines, and generic variant hard-filtering thresholds derived from human studies. Consequently, implementation of the Genome Analysis Toolkit (GATK) Best Practices framework, including machine learning-based variant quality score recalibration (VQSR), remains challenging in crop genomes. Here, we present a crop-adapted framework for unsupervised variant quality assessment and VQSR enabling advanced SNP and insertion-deletion (INDEL) discovery without predefined high-confidence reference variant sets. Using Brassica napus as a model, we use the Illumina 60k Brassica SNP array to generate a reference-specific truth set for data pre-processing and independent evaluation of an unsupervised machine-learning approach for constructing cohort-specific VQSR resources. Gaussian mixture model (GMM)-based clustering of multidimensional variant annotation profiles identifies high-, intermediate-, and low-quality variant classes, providing flexible training resources for VQSR without requiring labelled training data. We further validate the framework in diploid Brassica oleracea and hexaploid wheat (Triticum aestivum) across cohorts differing in population size, genetic diversity, and genome architecture. Despite population- and species-specific differences in variant annotation profiles, GMM-based clustering consistently identifies informative variant quality classes and enables cohort-specific recalibration of both SNPs and INDELs. Our results demonstrate that unsupervised machine learning can extend GATK Best Practices to crop species lacking comprehensive genomic resources, providing a scalable approach for generating high-quality variant datasets for crop genomics and downstream breeding applications.

plant biology↗

bioRxiv2026

Capturing the missing gene content of elite wheat by analysis of wheat landraces

There is a need to breed superior wheat cultivars to meet increasing global food demand. However, modern cultivars have undergone a substantial loss of genetic diversity due to intensive breeding. A pool of genetic diversity remains untapped in wheat landraces, and pangenomics can help identify genes of potential agronomic importance in these old lines that can be applied to accelerate wheat improvement. Here, we have constructed the largest wheat pangenome to date, representing 1,061 diverse individuals (827 landraces and 234 modern cultivars) from 47 countries across six continents. We identified 10,426 predicted gene models specific to landraces that are enriched for functions associated with disease resistance, abiotic stress adaptation, and symbiosis. Our results reveal that landraces harbour an extensive repertoire of genes that are absent from modern wheat cultivars and provide a foundational resource for the systematic reintroduction of adaptive variation to enhance wheat resilience and sustainability in the face of climate change.

plant biology↗

bioRxiv2026

Salmonella Typhi asparaginase-dependent activation of GCN2 promotes bacterial killing in murine macrophages

Many intracellular pathogens stimulate host cell stress by directly or indirectly causing an imbalance in host nutrients; depletion of amino acid pools in particular can act as a danger signal to infected cells. Using a restrictive host model of Salmonella enterica serovar Typhi (S. Typhi) infection, we identify early induction the integrated stress response (ISR) by viable bacteria, but not heat-killed bacteria. Genetic deletion of the amino acid sensing ISR kinase GCN2 (also known as EIF2AK4) prevented early ISR activation during S. Typhi infection, and murine macrophages lacking GCN2 show impaired bacterial clearance and decreased cytokine output. Supplementation of wildtype C57BL/6 murine macrophages with only the non-essential amino acid asparagine was sufficient to suppress S. Typhi-induced ISR activation and deletion of S. Typhi ansB, encoding an asparaginase, prevented ISR activation during infection. Pharmacological inhibition of mammalian target of rapamycin (mTOR), the other major amino acid sensing pathway in eukaryotic cells, prevented GCN2 activation and ISR induction in murine macrophages, indicating an upstream role for mTOR in signaling to GCN2. These findings suggest a role for the ISR in macrophage innate immune responses to S. Typhi infection and highlight a potential difference in nutrient-dependent signaling between the S. Typhi-susceptible human host and the restrictive murine host centered around asparagine, mTOR, and GCN2.

immunology↗

bioRxiv2026

Persistent declines in forest-dependent birds following active restoration of logged tropical forest in Borneo

O_LITropical forest restoration is critical for mitigating biodiversity loss and climate change, including in forests impacted by selective logging. Active restoration through liana cutting and enrichment tree planting can substantially accelerate carbon recovery, potentially reducing economic pressures to convert logged forests. But its long-term biodiversity impacts remain largely unknown. C_LIO_LIUsing over two decades of bird survey data from Borneos largest logged-forest restoration project, we quantified occupancy patterns for 176 species across primary, naturally regenerating, and actively restored logged forests spanning a 30+ year post-logging chronosequence. C_LIO_LIForest-dependent, threatened and near-threatened species generally declined through time in actively restored areas, whereas many species in naturally regenerating forests progressively recovered toward primary forest levels. Between 17-40% of 66 threatened or near-threatened species had consistently lower occupancies in actively restored than in naturally regenerating forest. Across species of global conservation concern, median occupancies in restored areas remained [~]22% below primary forest even 50 years after harvests, compared with only [~]6% lower under natural regeneration. C_LIO_LIArboreal insectivores, frugivores, and predatory species appeared most negatively affected by active restoration, with 27-49% of arboreal gleaning insectivores (of 62), 13-30% of arboreal frugivores (of 40), and one-third of predatory species (of 15) showing higher occupancy in naturally regenerating forests. Sallying insectivores also showed a possible but uncertain response, whereas ground-associated frugivores and insectivores were largely unaffected by restoration treatment. C_LIO_LIConcerningly, even 50 years post-logging, up to 52% of 50 high forest-dependency species retained distinct occupancies in actively restored compared with primary forest, suggesting persistent negative impacts of vine-cutting and/or tree planting activities on avian populations. C_LIO_LISynthesis and applications. Our findings indicate that despite substantial carbon benefits, active restoration within selectively logged forests may impede the recovery of forest-dependent biodiversity. This challenges the common assumption embedded within nature-based climate solutions that carbon and biodiversity outcomes will necessarily align. Nonetheless, despite the persistent declines in bird communities, actively restored forests continued to provide key habitat for many species. Active interventions may thus still contribute to broader biodiversity conservation objectives if they protect logged areas from conversion, potentially via carbon payments. C_LI

ecology↗

bioRxiv2025

A cortical signature of very preterm birth across development and its association with neurodevelopmental outcomes

Gestational age plays a crucial role in neurodevelopment, and individuals born very preterm (VPT; <32 weeks gestation) are at elevated risk for cognitive, behavioural and psychiatric problems across the lifespan. Better understanding of the impact of very preterm birth on cortical maturation trajectories could inform mechanistic insights into the origins of these sequelae. Here we compared cortical morphology between VPT individuals and full-term controls in three datasets spanning birth, childhood and adulthood. We identified a consistent cortical signature of VPT birth, characterized by reduced surface area and cortical folding in the frontal, temporal, parietal and insular regions, which persisted across development. Furthermore, in two large infant cohorts, we found that this cortical signature was significantly associated with neonatal clinical factors and with poorer motor outcomes at follow-up, suggesting its potential as a neuroimaging marker for long-term neurodevelopmental risk. Given that early motor development plays a key role in shaping infants interactions with the environment and supporting later cognitive and behavioural development, our findings provide insights into the neurobiological pathways linking VPT birth to subsequent neurodevelopmental difficulties.

neuroscience↗

bioRxiv2025

7 Tesla fMRI characterisation of the cortical-depth-dependentBOLD response in early human development

Human cortical development leading up to and around birth is crucial for lifelong brain function. Cortical activity can be studied using BOLD fMRI, however, previously limited sensitivity and spatial specificity has constrained understanding of how its emergence relates to functional cortical circuitry and neurovascular development at the mesoscale. To resolve this, we used ultra-high-field 7 Tesla MRI to acquire sub-millimetre resolution BOLD-fMRI data from 40 newborns and 4 adults. In all subjects, passive right-hand movement elicited localised, positive BOLD responses in contralateral primary somatosensory cortex. In newborns, depth-specific BOLD responses were still evident in the thinner cortex, with developmental changes in response temporal features and amplitudes at different depths. This provides insight into key rapidly evolving factors in early cortical development including neuronal function, vascular architecture, and neurovascular coupling. Our framework and findings provide a foundation for future studies of emerging cortical circuitry and how disruption leads to adverse outcomes.

developmental biology↗

bioRxiv2025

Phylogeny-driven design of broadly protective sarbecovirus receptor-binding domain nanoparticle vaccines

Vaccines against emerging SARS-CoV-2 variants and sarbecoviruses with pandemic potential must elicit a robust humoral immune response in a population imprinted with the SARS-CoV-2 spike (S) protein. Here, we designed protein nanoparticle (NP) vaccines co-displaying the SARS-CoV-2 BA.5, SARS-CoV-1, and BtKY72 receptor-binding domains (RBDs) with or without the Wuhan-Hu-1 (Wu) RBD. We show that these vaccines elicit cross-reactive and broadly neutralizing plasma antibody responses against SARS-CoV-2 variants and sarbecoviruses in naive and pre-immune animals. Immunization with multivalent RBD-NPs overcomes immune imprinting and elicits neutralizing antibodies and memory B cells specific for the BA.5, SARS-CoV-1, and BtKY72 RBDs in mRNA-1273-vaccinated non-human primates. Multivalent RBD-NPs outperform a monovalent Wu RBD-NP vaccine by providing superior protection in mice and non-human primates challenged with the vaccine-mismatched SARS-CoV-2 XBB.1.5 or the pre-emergent RsSHC014. These data support the use of multivalent RBD-NP vaccines for SARS-CoV-2 variants and sarbecoviruses in naive and pre-immune populations.

immunology↗

bioRxiv2024

mRNA-1273 vaccines adapted to JN.1 or KP.2 elicit cross-neutralizing responses against the JN.1 sublineages of SARS-CoV-2 in mice

The continued diversification of SARS-CoV-2 omicron lineage has given rise to the JN.1 variant and descendant strains (KP.2, KP.3, and XEC) that have prolonged the JN.1 infection wave. JN.1 and KP.2 show decreased susceptibility to neutralization sera in recipients of XBB.1.5 vaccine boosters, supporting the recent authorization of JN.1- and KP.2-matched mRNA vaccines in the United States, Europe, and other regions. We evaluated the immunogenicity of two updated monovalent variant-containing formulations of mRNA-1273 vaccines encoding the spike protein of the omicron subvariants JN.1 (mRNA-1273.167) and KP.2 (mRNA-1273.712) as compared with the monovalent XBB.1.5 vaccine (mRNA-1273.815). The vaccines were administered either as a two-dose primary series in naive mice or as a booster (third) dose in mice previously immunized with two-dose primary series of mRNA-1273 (ancestral strain). The neutralizing antibody response elicited by these vaccines against JN.1 subvariants (KP.3 and LA.2) and the recombinant strain (XEC), which achieved dominance in the United States during late 2024, was evaluated. Primary series immunization with either JN.1- or KP.2-matched vaccine elicited robust neutralizing antibody titers against the matched strains and effectively cross-neutralized KP.3, LA.2, and XEC, but not the antigenically distant XBB.1.5. Similarly, JN.1- and KP.2-matched vaccines administered as a booster (third) dose increased titers against the corresponding strains and JN.1-related subvariants, but not against XBB.1.5. These data suggest these strains are antigenically similar with relatively few spike differences between JN.1 and KP.2/JN.1-related subvariants. Our results demonstrate the potency of JN.1- and KP.2-containing mRNA-1273 vaccines in neutralizing the matched variants and their utility in cross-neutralizing JN.1-related subvariants KP.3, LA.2, and XEC. Taken together, these data suggest that the licensed JN.1 and KP.2 mRNA vaccines are likely to continue to protect against the emerging strains as the JN.1 lineage further evolves.

immunology↗

bioRxiv2024

Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein

SARS-CoV-2 mRNA vaccines induce robust and persistent germinal centre (GC) B cell responses in humans. It remains unclear how the continuous evolution of the virus impacts the breadth of the induced GC B cell response. Using ultrasound-guided fine needle aspiration, we examined draining lymph nodes of nine healthy adults following bivalent booster immunization. We show that 77.8% of the B cell clones in the GC expressed as representative monoclonal antibodies recognized the spike protein, with a third (37.8%) of these targeting the receptor binding domain (RBD). Strikingly, only one RBD-targeting mAb, mAb-52, neutralized all tested SARS- CoV-2 strains, including the recent KP.2 variant. mAb-52 utilizes the IGHV3-66 public clonotype, protects hamsters challenged against the EG.5.1 variant and targets the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Finally, we show that the remarkable breadth of mAb-52 is due to the somatic hypermutations accumulated within vaccine-induced GC reaction. One Sentence SummaryBooster SARS-CoV-2 mRNA vaccine recruits and broadens GC B cell responses targeting a highly conserved site on receptor binding domain of spike glycoprotein.

immunology↗

bioRxiv2024

The developing Human Connectome Project fetal functional MRI release: Methods and data structures

Recent advances in fetal fMRI present a new opportunity for neuroscience to study functional human brain connectivity at the time of its emergence. Progress in the field however has been hampered by the lack of openly available datasets that can be exploited by researchers across disciplines to develop methods that would address the unique challenges associated with imaging and analysing functional brain in utero, such as unconstrained head motion, dynamically evolving geometric distortions, or inherently low signal-to-noise ratio. Here we describe the developing Human Connectome Projects release of the largest open access fetal fMRI dataset to date, containing 275 scans from 255 fetuses and spanning the period of 20.86 to 38.29 post-menstrual weeks. We present a systematic approach to its pre-processing, implementing multi-band soft SENSE reconstruction, dynamic distortion corrections via phase unwrapping method, slice-to-volume reconstruction and a tailored temporal filtering model, with attention to the prominent sources of structured noise in the in utero fMRI. The dataset is accompanied with an advanced registration infrastructure, enabling group-level data fusion, and contains outputs from the main intermediate processing steps. This allows for various levels of data exploration by the imaging and neuroscientific community, starting from the development of robust pipelines for anatomical and temporal corrections to methods for elucidating the development of functional connectivity in utero. By providing a high-quality template for further method development and benchmarking, the release of the dataset will help to advance fetal fMRI to its deserved and timely place at the forefront of the efforts to build a life-long connectome of the human brain.

neuroscience↗

bioRxiv2024

A spatio-temporaral atlas of the growing brain for fMRI studies

Spatio-temporal atlases of the growing brain can help when building models of brain development, not only for anatomical structure, but also for the changing patterns of activation within the brain. In this paper, we build such an age-dependent atlas using registrations among a large number of anatomical datasets, acquired from neonatal subjects of different ages, and followed by kernel-based regression. fMRI activation data are then registered to this atlas to build a model of the development of brain networks, such as the default and motor networks, at this early age.

neuroscience↗

bioRxiv2024

Differential maturation of the brain networks required for the sensory, emotional and cognitive aspects of pain in human newborns

Pain is multidimensional and complex, including sensory-discriminative, affective- motivational, and cognitive-evaluative components. While the concept of pain is learned through life experience, it is not known when and how the brain networks that are required to encode these different dimensions of pain develop. Using the two largest databases of human brain magnetic resonance (MR) images in the world - the developing Human Connectome Project and the Human Connectome Project - we have mapped the development of the neural pathways required for pain perception in the human brain in infants from <32 weeks to 42 weeks postmenstrual age (n = 372), compared to adults (n = 98). Partial correlation analysis of 15 mins resting BOLD signal between all possible pairwise combinations of 12 pain-related regions of interest showed that overall functional connectivity is significantly weaker in 32- week infants compared to adults. However, over the following weeks, significantly different developmental patterns of connectivity emerge in sensory-discriminative, affective- motivational, and cognitive-evaluative pain networks. The first subnetwork to reach adult levels in strength and proportion of connections is the sensory-discriminative subnetwork (34- 36 weeks PMA), followed by the affective-motivational subnetwork (36-38 weeks PMA), while the cognitive-evaluative subnetwork has still not reached adult levels at 42 weeks. This study reveals a previously unknown pattern of postnatal development of connectome subnetworks necessary for mature pain processing. The brain networks that form the infrastructure to encode different components of pain experience, change rapidly in the equivalent of the last gestational trimester but are still immature at the time of normal birth. Newborn neural pathways required for mature pain processing in the brain are incomplete in newborns compared to adults, particularly with respect to the emotional and evaluative aspects of pain. This data suggests that pain-related networks may have distinct periods of vulnerability to untimely noxious procedures during hospitalization, particularly in preterm infants.

neuroscience↗

bioRxiv2024

Exploring functional connectivity in clinical and data-driven groups of preterm and term adults

BackgroundAdults born very preterm (i.e., at <33 weeks gestation) are more susceptible to long-lasting structural and functional brain alterations and cognitive and socio-emotional difficulties, compared to full-term controls. However, behavioural heterogeneity within very preterm and full-term individuals makes it challenging to find biomarkers of specific outcomes. To address these questions, we parsed brain-behaviour heterogeneity in participants subdivided according to their clinical birth status (very preterm vs full-term) and/or data-driven behavioural phenotype (regardless of birth status). MethodsThe Network Based Statistic approach was used to identify topological components of resting state functional connectivity differentiating between i) 116 very preterm and 83 full-term adults (43% and 57% female, respectively), and ii) data-driven behavioural subgroups identified using consensus clustering (n= 156, 46% female). Age, sex, socio-economic status, and in-scanner head motion were used as confounders in all analyses. Post-hoc two-way group interactions between clinical birth status and behavioural data-driven subgrouping classification labels explored whether functional connectivity differences between very preterm and full-term adults varied according to distinct behavioural outcomes. ResultsVery preterm compared to full-term adults had poorer scores in selective measures of cognitive and socio-emotional processing and displayed complex patterns of hyper- and hypo-connectivity in subsections of the default mode, visual, and ventral attention networks. Stratifying the study participants in terms of their behavioural profiles (irrespective of birth status), identified two data-driven subgroups: An "At-risk" subgroup, characterised by increased cognitive, mental health, and socio-emotional difficulties, displaying hypo-connectivity anchored in frontal opercular and insular regions, relative to a "Resilient" subgroup with more favourable outcomes. No significant interaction was noted between clinical birth status and behavioural data-driven subgrouping classification labels in terms of functional connectivity. ConclusionsFunctional connectivity differentiating between very preterm and full-term adults was dissimilar to functional connectivity differentiating between the data-driven behavioural subgroups. We speculate that functional connectivity alterations observed in very preterm relative to full-term adults may confer both risk and resilience to developing behavioural sequelae associated with very preterm birth, while the localised functional connectivity alterations seen in the "At-risk" subgroup relative to the "Resilient" subgroup may underlie less favourable behavioural outcomes in adulthood, irrespective of birth status.

developmental biology↗

bioRxiv2023

Adaptive gene loss in the common bean pan-genome during range expansion and domestication

The common bean (Phaseolus vulgaris L.) is a crucial grain legume crop [1,2] whose life history offers an ideal evolutionary model to identify and study adaptive variants in wild and domestication populations [3]. Here we present the first common bean pan-genome based on five high-quality genomes and whole-genome reads representing 339 genotypes. We found [~]243 Mb of additional sequences containing 7,495 protein-coding genes missing from the reference, constituting 51% of the total presence/absence variations (PAVs). There were more putatively deleterious mutations in PAVs than core genes, probably reflecting the lower effective population size of PAVs as well as fitness advantages due to the purging effect of gene loss. Our results suggest strong pan-genome shrinkage occurred during wild range expansion from Mexico to South America, with more PAV loss per individual in Andean vs Mesoamerican populations. Selection signatures during wild spreading and domestication were also associated with PAV loss involved in important adaptive traits. Our findings provide evidence that partial or complete gene loss was a key adaptive trait leading to localized and genome-wide reductions. This novel result has major implications for the understanding of the process of plant adaptation and claims for a paradigm shift in evolutionary genetics. Moreover, the common bean pan-genome is a valuable resource for food legume research and breeding towards climate change mitigation, and sustainable agriculture.

evolutionary biology↗

bioRxiv2023

Surface Generative Modelling of Neurodevelopmental Trajectories

Cortical neurodevelopment is sensitive to disruption following preterm birth, with lasting impact on cognitive outcomes. The creation of generative models of neurodevelopment could aid clinicians in identifying atrisk subjects but is complicated by the degree of subject variability in cortical folding, and significant heterogeneity in the effect of preterm birth. In this work, we propose a graph convolutional generative adversarial network (GAN) and a training scheme to simulate neonatal cortical surface developmental trajectories. The proposed model is used to smoothly modify two cortical phenotypes: post-menstrual age at scan (PMA) and gestational age at birth (GA) on data from the developing Human Connectome Project (dHCP) [1]. The synthetic images were validated with an independently trained regression network, and compared against follow up scans, indicating that the model can realistically age individuals whilst preserving subject-specific cortical morphology. Deviation between simulated healthy scans, and preterm follow up scans generated a metric of individual atypicality, which improved prediction of 18-month cognitive outcome over GA alone.

neuroscience↗

bioRxiv2023

Gradient organisation of functional connectivity within resting state networks is present from 25 weeks gestation in the human fetal brain

During the third trimester of human gestation, the structure and function of the fetal brain is developing rapidly, laying the foundation for its connectivity framework across the lifespan. During this juncture, resting state functional MRI can be used to identify resting state networks (RSNs) which mature across gestation to resemble canonical RSNs at full term. However, the emergence of finer grain organisation of connectivity within these RSNs in the fetal brain is unknown. Using in-utero resting state fMRI, we performed connectopic mapping analysis to explore the presence of gradients in functional connectivity organisation of 11 cortical RSNs, known as connectopic maps in fetuses aged 25-37 weeks gestation (GW). We hypothesised that, if present, development of connectopic maps would be network specific in the third trimester of gestation, such that this property would be present within the earlier maturing primary sensory and motor networks before those associated with higher association function. In keeping with this, we found smooth connectopic maps in all of the studied RSNs from 25 GW, with the most spatially consistency across gestational age in the primary sensory and motor networks. Voxel-wise permutation testing of the connectopic maps identified local clusters of voxels within networks that significantly covaried with age, specifically in multisensory processing areas, suggesting multisensory processing may be developing during this period. Our analysis shows that functional gradient organisation is already established in the fetal brain and develops throughout gestation, which has strong implications for understanding how cortical organisation subserves the emergence of behaviour in the ensuing period.

neuroscience↗

bioRxiv2023

Comparative genomics of Japanese encephalitis virus shows low rates of recombination and a suite of sites under episodic diversifying selection

Japanese encephalitis virus (JEV) is the dominant cause of viral encephalitis in the Asian region with 100,000 cases and 25,000 deaths reported annually. The genome is comprised of a single polyprotein that encodes three structural and seven non-structural proteins. We collated a dataset of 347 complete genomes from a number of public databases, and analysed the data for recombination, evolutionary selection and phylogenetic structure. There are low rates of recombination in JEV, subsequently recombination is not a major evolutionary force shaping JEV. We found a strong overall signal of purifying selection in the genome, which is the main force affecting the evolutionary dynamics in JEV. There are also a small number of genomic sites under episodic diversifying selection, especially in the envelope protein and non-structural proteins 3 and 5. Overall, these results support previous analyses of JEV evolutionary genomics and provide additional insight into the evolutionary processes shaping the distribution and adaptation of this important pathogenic arbovirus. Author SummaryThis comparative study of Japanese Encephalitis Virus is the largest genomic analysis of the virus to date. We undertake a suite of analyses to investigate phylogenetic relationships, rates of recombination and patterns of genomic selection. We show that recombination is not a significant driver of evolution in JEV, demonstrate support for previous phylogenetic reconstructions of the virus, and find a number of sites across the genome under episodic diversifying selection. These adaptive hotspots of evolution serve as key genomic points for the adaptive evolution of this important vector borne pathogen.

microbiology↗

bioRxiv2023

Local haplotype visualization for trait association analysis with crosshap

SummaryGWAS excels at harnessing dense genomic variant datasets to identify candidate regions responsible for producing a given phenotype. However, GWAS and traditional fine-mapping methods do not provide insight into the complex local landscape of linkage that contains and has been shaped by the causal variant(s). Here, we present crosshap, an R package that performs robust density-based clustering of variants based on their linkage profiles to capture haplotype structures in a local genomic region of interest. Following this, crosshap is equipped with visualization tools for choosing optimal clustering parameters ({varepsilon}) before producing an intuitive figure that provides an overview of the complex relationships between linked variants, haplotype combinations, phenotypic traits and metadata. Availability and implementationThe crosshap package is freely available under the MIT license and can be downloaded directly from CRAN with R>4.0.0. The development version is available on GitHub alongside issue support (https://github.com/jacobimarsh/crosshap). Tutorial vignettes and documentation are available (https://jacobimarsh.github.io/crosshap/).

bioinformatics↗