Blinding Is Seeing: A Single-Centre Study Into the Viability of Auto-Injectors for Blinded-Drug Administration in Randomised Controlled Trials.

Objective The aim of the study was to assess the viability of auto-injector systems (A-INJ) for preserving investigator blinding in randomized controlled trials (RCT). Background Blinding refers to the concealment of group allocation from one or more individuals involved in a clinical research study. In the dosing of subcutaneous (SC) and intramuscular (IM) investigational medicinal products (IMP), specific challenges arise in maintaining investigator blinding. These challenges primarily involve the active injectate's viscosity and visual appearance (colour/translucency) in comparison to the placebo. Existing methods to control these issues are not perfect. Common approaches include using unblinded investigators or applying films or additives to make the active and placebo injectates appear similar. Method A single-centre experimental and descriptive study was carried out to compare the use of an A-INJ (Owen Mumford, Autoject 2) with the use of a conventional syringe (CS) in delivering a 1 ml dose of both placebo and reference IMP. The percentage delivery of the injectate was compared between the A-INJ IMP and placebo groups. Additionally, eight trained research physicians serving as investigators recorded their assessments of safety and effectiveness after performing serial injections with the A-INJ into a human-tissue analogue. Results Overall, a mean of 95.38% of 1ml placebo injectate was released from the A-INJ, compared to 96.00% from the CS. A total of 94.715% of 1 ml IMP injectate was released from the A-INJ, as opposed to 94.74% from the CS. Independent t-test analyses showed no statistical significance between the experimental arms. The mean administration time was 8.5 seconds. Investigators were unable to differentiate between the two solutions when using the A-INJ. There were no recorded concerns about investigators becoming unblinded, which stands in contrast to concerns associated with using the CS. Conclusion In assessing the viability of A-INJ use in RCTs, we noted a marked improvement when blinding was used. A-INJ systems effectively administer both placebo and active injectates, thereby maintaining the benefit of blinding without the need to alter the placebo through the addition of colourants or viscosity additives. While audio cues from the A-INJ and the time required to administer the injectate pose challenges, solutions are suggested. Although our findings are preliminary, they add to the existing literature on the advantages of A-INJs for administering injectable compounds and offer new perspectives on their utility in RCTs.

The Reliability of Auto-Injectors in Clinical Use: A Systematic Review.

Auto-injectors are medical devices designed for the self-administration of injections by patients and for easy administration by healthcare professionals in emergency situations. Although they vary in design and application, auto-injectors are typically built around a spring-loaded syringe. Despite their widespread use in a variety of clinical settings, there have been limited attempts to assess their reliability. This systematic review investigates the reliability of auto-injectors, identifies common causes of failure, and summarizes the overall rate of malfunction. A systematic review of research published on the PubMed and Cochrane Library databases was performed in July 2022. The relevant studies were assessed for their methodological quality and risk of bias prior to extracting key study outcomes on auto-injector reliability. Finally, a summary rate covering all eligible studies was calculated.  The search identified a total of 110 articles, of which ten were found to be suitable for inclusion. The risk of bias was low, and the methodological quality was high across the ten studies. Out of a total of 2,964 injections administered from an auto-injector, there were 12 device malfunctions, giving a summary rate of 0.40% (±0.23) auto-injector failures. The causes of malfunction varied in nature, with the majority of cases (58.3%) not being specified or not identified. This review has demonstrated that auto-injectors are reliable devices. Although further research on the nature of malfunctions is needed, the low rate of malfunctions supports training programs for healthcare professionals and patients on the optimum use and maintenance of auto-injectors. It provides a rationale for their continued development.

Robotic-assisted knee replacement surgery & infection: A historical foundation, systematic review and meta-analysis.

Background: An increasing proportion of Knee arthroplasty is performed using robotic-assisted surgical techniques. This study sought to use a meta-analytical approach to establish summary rates of surgical site infection in robotic-assisted procedures and compare the rate of deep infections to those seen in conventional knee arthroplasty. Methods: This study performed a literature search across four online databases to establish a summary rate of surgical site infection across two categories: deep infection and superficial and pin-site infections. This was processed with the aid of a bespoke data-extraction tool. Risk of Bias analysis was performed using the Cochrane RoB2 tool. Meta-analysis was then performed with tests for heterogeneity and a DerSimonian-Laird random effects model. Results: A total of 17 studies were identified as appropriate for inclusion in the meta-analysis. The summary rate of overall surgical site infections within one year of robotic knee arthroplasty was found to be 0.568% (SE = 0.183, 95% CI = 0.209-0.927). Deep infections fell to 0.154% (SE = 0.069, 95% CI = 0.018-0.290) and to 0.347% (SE = 0.109, 95% CI = 0.133-0.561) in superficial and pin-site infections. Conclusion: The surgical site infection rates were found to be low across robotic knee arthroplasty. Further research is required to prove its superiority compared to the conventional, non-robotic technique.

Clinician and computer: a study on doctors' perceptions of artificial intelligence in skeletal radiography.

BACKGROUND: Traumatic musculoskeletal injuries are a common presentation to emergency care, the first-line investigation often being plain radiography. The interpretation of this imaging frequently falls to less experienced clinicians despite well-established challenges in reporting. This study presents novel data of clinicians' confidence in interpreting trauma radiographs, their perception of AI in healthcare, and their support for the development of systems applied to skeletal radiography. METHODS: A novel questionnaire was distributed through a network of collaborators to clinicians across the Southeast of England. Over a three-month period, responses were compiled into a database before undergoing statistical review. RESULTS: The responses of 297 participants were included. The mean self-assessed knowledge of AI in healthcare was 3.68 out of ten, with significantly higher knowledge reported by the most senior doctors (Specialty Trainee/Specialty Registrar or above = 4.88). 13.8% of participants reported an awareness of AI in their clinical practice. Overall, participants indicated substantial favourability towards AI in healthcare (7.87) and in AI applied to skeletal radiography (7.75). There was a preference for a hypothetical system indicating positive findings rather than ruling as negative (7.26 vs 6.20). CONCLUSIONS: This study identifies clear support, amongst a cross section of student and qualified doctors, for both the general use of AI technology in healthcare and in its application to skeletal radiography for trauma. The development of systems to address this demand appear well founded and popular. The engagement of a small but reticent minority should be sought, along with improving the wider education of doctors on AI.

Reporting errors in plain radiographs for lower limb trauma-a systematic review and meta-analysis.

INTRODUCTION: Plain radiographs are a globally ubiquitous means of investigation for injuries to the musculoskeletal system. Despite this, initial interpretation remains a challenge and inaccuracies give rise to adverse sequelae for patients and healthcare providers alike. This study sought to address the limited, existing meta-analytic research on the initial reporting of radiographs for skeletal trauma, with specific regard to diagnostic accuracy of the most commonly injured region of the appendicular skeleton, the lower limb. METHOD: A prospectively registered, systematic review and meta-analysis was performed using published research from the major clinical-science databases. Studies identified as appropriate for inclusion underwent methodological quality and risk of bias analysis. Meta-analysis was then performed to establish summary rates for specificity and sensitivity of diagnostic accuracy, including covariates by anatomical site, using HSROC and bivariate models. RESULTS: A total of 3887 articles were screened, with 10 identified as suitable for analysis based on the eligibility criteria. Sensitivity and specificity across the studies were 93.5% and 89.7% respectively. Compared with other anatomical subdivisions, interpretation of ankle radiographs yielded the highest sensitivity and specificity, with values of 98.1% and 94.6% respectively, and a diagnostic odds ratio of 929.97. CONCLUSION: Interpretation of lower limb skeletal radiographs operates at a reasonably high degree of sensitivity and specificity. However, one in twenty true positives is missed on initial radiographic interpretation and safety netting systems need to be established to address this. Virtual fracture clinic reviews and teleradiology services in conjunction with novel technology will likely be crucial in these circumstances.

Clinician and computer: a study on patient perceptions of artificial intelligence in skeletal radiography.

BACKGROUND: Up to half of all musculoskeletal injuries are investigated with plain radiographs. However, high rates of image interpretation error mean that novel solutions such as artificial intelligence (AI) are being explored. OBJECTIVES: To determine patient confidence in clinician-led radiograph interpretation, the perception of AI-assisted interpretation and management, and to identify factors which might influence these views. METHODS: A novel questionnaire was distributed to patients attending fracture clinic in a large inner-city teaching hospital. Categorical and Likert scale questions were used to assess participant demographics, daily electronics use, pain score and perceptions towards AI used to assist in interpretation of their radiographs, and guide management. RESULTS: 216 questionnaires were included (M=126, F=90). Significantly higher confidence in clinician rather than AI-assisted interpretation was observed (clinician=9.20, SD=1.27 vs AI=7.06, SD=2.13), 95.4% reported favouring clinician over AI-performed interpretation in the event of disagreement.Small positive correlations were observed between younger age/educational achievement and confidence in AI-assistance. Students demonstrated similarly increased confidence (8.43, SD 1.80), and were over-represented in the minority who indicated a preference for AI-assessment over their clinicians (50%). CONCLUSIONS: Participant's held the clinician's assessment in the highest regard and expressed a clear preference for it over the hypothetical AI assessment. However, robust confidence scores for the role of AI-assistance in interpreting skeletal imaging suggest patients view the technology favourably.Findings indicate that younger, more educated patients are potentially more comfortable with a role for AI-assistance however further research is needed to overcome the small number of responses on which these observations are based.

Independent evolution of ancestral and novel defenses in a genus of toxic plants (Erysimum, Brassicaceae).

Phytochemical diversity is thought to result from coevolutionary cycles as specialization in herbivores imposes diversifying selection on plant chemical defenses. Plants in the speciose genus Erysimum (Brassicaceae) produce both ancestral glucosinolates and evolutionarily novel cardenolides as defenses. Here we test macroevolutionary hypotheses on co-expression, co-regulation, and diversification of these potentially redundant defenses across this genus. We sequenced and assembled the genome of E. cheiranthoides and foliar transcriptomes of 47 additional Erysimum species to construct a phylogeny from 9868 orthologous genes, revealing several geographic clades but also high levels of gene discordance. Concentrations, inducibility, and diversity of the two defenses varied independently among species, with no evidence for trade-offs. Closely related, geographically co-occurring species shared similar cardenolide traits, but not glucosinolate traits, likely as a result of specific selective pressures acting on each defense. Ancestral and novel chemical defenses in Erysimum thus appear to provide complementary rather than redundant functions.

Plants are often attacked by insects and other herbivores. As a result, they have evolved to defend themselves by producing many different chemicals that are toxic to these pests. As producing each chemical costs energy, individual plants often only produce one type of chemical that is targeted towards their main herbivore. Related species of plants often use the same type of chemical defense so, if a particular herbivore gains the ability to cope with this chemical, it may rapidly become an important pest for the whole plant family. To escape this threat, some plants have gained the ability to produce more than one type of chemical defense. Wallflowers, for example, are a group of plants in the mustard family that produce two types of toxic chemicals: mustard oils, which are common in most plants in this family; and cardenolides, which are an innovation of the wallflowers, and which are otherwise found only in distantly related plants such as foxglove and milkweed. The combination of these two chemical defenses within the same plant may have allowed the wallflowers to escape attacks from their main herbivores and may explain why the number of wallflower species rapidly increased within the last two million years. Züst et al. have now studied the diversity of mustard oils and cardenolides present in many different species of wallflower. This analysis revealed that almost all of the tested wallflower species produced high amounts of both chemical defenses, while only one species lacked the ability to produce cardenolides. The levels of mustard oils had no relation to the levels of cardenolides in the tested species, which suggests that the regulation of these two defenses is not linked. Furthermore, Züst et al. found that closely related wallflower species produced more similar cardenolides, but less similar mustard oils, to each other. This suggests that mustard oils and cardenolides have evolved independently in wallflowers and have distinct roles in the defense against different herbivores. The evolution of insect resistance to pesticides and other toxins is an important concern for agriculture. Applying multiple toxins to crops at the same time is an important strategy to slow the evolution of resistance in the pests. The findings of Züst et al. describe a system in which plants have naturally evolved an equivalent strategy to escape their main herbivores. Understanding how plants produce multiple chemical defenses, and the costs involved, may help efforts to breed crop species that are more resistant to herbivores and require fewer applications of pesticides.

Seasonal and climatic variation in the incidence of adult acute appendicitis: a seven year longitudinal analysis.

BACKGROUND: Acute appendicitis represents an extremely common surgical emergency, yet its aetiology remains uncertain. A multifactorial understanding of its causation has emerged along with increasing evidence of seasonal variation. This study seeks to find evidence for such a circannual trend within the United Kingdom (UK), and further assess key meteorological indicators which may be causative of any such variation. METHODS: The patient records of a region health body in the North East of England were retrospectively assessed over a 7-year period. The incident cases of acute appendicitis were recorded and averaged by month before undergoing statistical analysis for variation and correlation with average temperature, sunlight hours, and rainfall. RESULTS: The incidence of acute appendicitis revealed significant seasonal variation with only 38 incident cases in the months of January compared to 73 in July, a 92.1% increase. Only a weak correlation was seen between incidence and average sunlight hours/rainfall, however a significant, positive correlation was found between incidence and average temperature (r = 0.58, p = 0.048). CONCLUSION: Compelling evidence is found to support the existence of a circannual trend for acute appendicitis. Data suggests a seasonal peak in the month of July, accompanied by a low in January, a finding that develops the understanding of this trend from previously equivocal research in the UK. A clear correlation is also established between the incidence of acute appendicitis and average temperature. The 92.1% increase between the coolest and warmest months suggests a greater magnitude for this as a risk factor than has previously been shown.

Reporting Discrepancy Resolved by Findings and Time in 2947 Emergency Department Ankle X-rays.

AIMS: To identify common errors in ankle X-ray reporting between initial interpretation and final assessment at the virtual fracture clinic. Also, to assess time of initial reporting as a causative factor for discrepancy. METHODS: Two thousand nine hundred forty-seven final reports were reviewed by standard of agreement to the initial interpretation. Where discrepancy was found, it was classified and collated by specific finding. Comparison was made between reports with discrepancy and the complete dataset, allowing rates of error by finding to be established. The reports containing discrepancy were further classified by time period, this was compared against an expected value to establish if initial reporting outside of routine working hours was as accurate as that conducted within routine working hours. RESULTS: 94.4% of reports were in agreement with the initial interpretation, 2.9% contained minor discrepancy, and 2.7% major discrepancy. In 45.6% of reports there was no radiologically observable injury. 16.4% of reports contained a lateral malleolar fracture, most commonly Weber type B. 40.0% of all navicular fractures, and 33.3% of all cuboidal fractures were not commented upon in the initial reporting. Lower rates of more frequently observed findings were missed with 2.5% of Weber type B fractures not commented upon. An increased proportion of major discrepancy reports were generated from 00:00 to 07:59 (expected = 15.0%, observed = 22.2%; p = 0.07908). Similarly, a greater than expected number of minor discrepancy reports were found between 20:00 and 23:59 (expected = 18.0%, observed = 34.1%, p = 0.00025). CONCLUSIONS: The initial reporting of ankle X-rays in the emergency department is performed to a high standard, however serious missed findings emphasise the need for timely senior review. Reporters should increase their awareness of navicular, cuboid, talar, and Weber A fractures which were missed at disproportionate rates. This study also finds evidence to support increased rates of error in initial reporting of ankle X-rays outside of normal working hours (17:00-07:59), particularly with a significantly increased rate of minor discrepancy seen from 20:00 to 23:59.

Genes conserved for arbuscular mycorrhizal symbiosis identified through phylogenomics.

Arbuscular mycorrhizal symbiosis (AMS), a widespread mutualistic association of land plants and fungi(1), is predicted to have arisen once, early in the evolution of land plants(2-4). Consistent with this notion, several genes required for AMS have been conserved throughout evolution(5) and their symbiotic functions preserved, at least between monocot and dicot plants(6,7). Despite its significance, knowledge of the plants' genetic programme for AMS is limited. To date, most genes required for AMS have been found through commonalities with the evolutionarily younger nitrogen-fixing Rhizobium legume symbiosis (RLS)(8) or by reverse genetic analyses of differentially expressed candidate genes(9). Large sequence-indexed insertion mutant collections and recent genome editing technologies have vastly increased the power of reverse genetics but selection of candidate genes, from the thousands of genes that change expression during AMS, remains an arbitrary process. Here, we describe a phylogenomics approach to identify genes whose evolutionary history predicts conservation for AMS and we demonstrate the accuracy of the predictions through reverse genetics analysis. Phylogenomics analysis of 50 plant genomes resulted in 138 genes from Medicago truncatula predicted to function in AMS. This includes 15 genes with known roles in AMS. Additionally, we demonstrate that mutants in six previously uncharacterized AMS-conserved genes are all impaired in AMS. Our results demonstrate that phylogenomics is an effective strategy to identify a set of evolutionarily conserved genes required for AMS.

Comparative genomics and phylogenetic discordance of cultivated tomato and close wild relatives.

Background. Studies of ancestry are difficult in the tomato because it crosses with many wild relatives and species in the tomato clade that have diverged very recently. As a result, the phylogeny in relation to its closest relatives remains uncertain. By using the coding sequence from Solanum lycopersicum, S. galapagense, S. pimpinellifolium, S. corneliomuelleri, and S. tuberosum and the genomic sequence from S. lycopersicum 'Heinz', an heirloom line, S. lycopersicum 'Yellow Pear', and two of cultivated tomato's closest relatives, S. galapagense and S. pimpinellifolium, we have aimed to resolve the phylogenies of these closely related species as well as identify phylogenetic discordance in the reference cultivated tomato. Results. Divergence date estimates suggest that the divergence of S. lycopersicum, S. galapagense, and S. pimpinellifolium happened less than 0.5 MYA. Phylogenies based on 8,857 coding sequences support grouping of S. lycopersicum and S. galapagense, although two secondary trees are also highly represented. A total of 25 genes in our analysis had sites with evidence of positive selection along the S. lycopersicum lineage. Whole genome phylogenies showed that while incongruence is prevalent in genomic comparisons between these genotypes, likely as a result of introgression and incomplete lineage sorting, a primary phylogenetic history was strongly supported. Conclusions. Based on analysis of these genotypes, S. galapagense appears to be closely related to S. lycopersicum, suggesting they had a common ancestor prior to the arrival of an S. galapagense ancestor to the Galápagos Islands, but after divergence of the sequenced S. pimpinellifolium. Genes showing selection along the S. lycopersicum lineage may be important in domestication or selection occurring post-domestication. Further analysis of intraspecific data in these species will help to establish the evolutionary history of cultivated tomato. The use of an heirloom line is helpful in deducing true phylogenetic information of S. lycopersicum and identifying regions of introgression from wild species.

The Sol Genomics Network (SGN)--from genotype to phenotype to breeding.

The Sol Genomics Network (SGN, http://solgenomics.net) is a web portal with genomic and phenotypic data, and analysis tools for the Solanaceae family and close relatives. SGN hosts whole genome data for an increasing number of Solanaceae family members including tomato, potato, pepper, eggplant, tobacco and Nicotiana benthamiana. The database also stores loci and phenotype data, which researchers can upload and edit with user-friendly web interfaces. Tools such as BLAST, GBrowse and JBrowse for browsing genomes, expression and map data viewers, a locus community annotation system and a QTL analysis tools are available. A new tool was recently implemented to improve Virus-Induced Gene Silencing (VIGS) constructs called the SGN VIGS tool. With the growing genomic and phenotypic data in the database, SGN is now advancing to develop new web-based breeding tools and implement the code and database structure for other species or clade-specific databases.

The Sol Genomics Network (solgenomics.net): growing tomatoes using Perl.

The Sol Genomics Network (SGN; http://solgenomics.net/) is a clade-oriented database (COD) containing biological data for species in the Solanaceae and their close relatives, with data types ranging from chromosomes and genes to phenotypes and accessions. SGN hosts several genome maps and sequences, including a pre-release of the tomato (Solanum lycopersicum cv Heinz 1706) reference genome. A new transcriptome component has been added to store RNA-seq and microarray data. SGN is also an open source software project, continuously developing and improving a complex system for storing, integrating and analyzing data. All code and development work is publicly visible on GitHub (http://github.com). The database architecture combines SGN-specific schemas and the community-developed Chado schema (http://gmod.org/wiki/Chado) for compatibility with other genome databases. The SGN curation model is community-driven, allowing researchers to add and edit information using simple web tools. Currently, over a hundred community annotators help curate the database. SGN can be accessed at http://solgenomics.net/.

Auto-validating von Neumann rejection sampling from small phylogenetic tree spaces.

BACKGROUND: In phylogenetic inference one is interested in obtaining samples from the posterior distribution over the tree space on the basis of some observed DNA sequence data. One of the simplest sampling methods is the rejection sampler due to von Neumann. Here we introduce an auto-validating version of the rejection sampler, via interval analysis, to rigorously draw samples from posterior distributions over small phylogenetic tree spaces. RESULTS: The posterior samples from the auto-validating sampler are used to rigorously (i) estimate posterior probabilities for different rooted topologies based on mitochondrial DNA from human, chimpanzee and gorilla, (ii) conduct a non-parametric test of rate variation between protein-coding and tRNA-coding sites from three primates and (iii) obtain a posterior estimate of the human-neanderthal divergence time. CONCLUSION: This solves the open problem of rigorously drawing independent and identically distributed samples from the posterior distribution over rooted and unrooted small tree spaces (3 or 4 taxa) based on any multiply-aligned sequence data.

Estimation of 2Nes from temporal allele frequency data.

We develop a new method for estimating effective population sizes, Ne, and selection coefficients, s, from time-series data of allele frequencies sampled from a single diallelic locus. The method is based on calculating transition probabilities, using a numerical solution of the diffusion process, and assuming independent binomial sampling from this diffusion process at each time point. We apply the method in two example applications. First, we estimate selection coefficients acting on the CCR5-delta 32 mutation on the basis of published samples of contemporary and ancient human DNA. We show that the data are compatible with the assumption of s = 0, although moderate amounts of selection acting on this mutation cannot be excluded. In our second example, we estimate the selection coefficient acting on a mutation segregating in an experimental phage population. We show that the selection coefficient acting on this mutation is approximately 0.43.

Genome-wide patterns of nucleotide polymorphism in domesticated rice.

Domesticated Asian rice (Oryza sativa) is one of the oldest domesticated crop species in the world, having fed more people than any other plant in human history. We report the patterns of DNA sequence variation in rice and its wild ancestor, O. rufipogon, across 111 randomly chosen gene fragments, and use these to infer the evolutionary dynamics that led to the origins of rice. There is a genome-wide excess of high-frequency derived single nucleotide polymorphisms (SNPs) in O. sativa varieties, a pattern that has not been reported for other crop species. We developed several alternative models to explain contemporary patterns of polymorphisms in rice, including a (i) selectively neutral population bottleneck model, (ii) bottleneck plus migration model, (iii) multiple selective sweeps model, and (iv) bottleneck plus selective sweeps model. We find that a simple bottleneck model, which has been the dominant demographic model for domesticated species, cannot explain the derived nucleotide polymorphism site frequency spectrum in rice. Instead, a bottleneck model that incorporates selective sweeps, or a more complex demographic model that includes subdivision and gene flow, are more plausible explanations for patterns of variation in domesticated rice varieties. If selective sweeps are indeed the explanation for the observed nucleotide data of domesticated rice, it suggests that strong selection can leave its imprint on genome-wide polymorphism patterns, contrary to expectations that selection results only in a local signature of variation.

Dependence of paracentric inversion rate on tract length.

BACKGROUND: We develop a Bayesian method based on MCMC for estimating the relative rates of pericentric and paracentric inversions from marker data from two species. The method also allows estimation of the distribution of inversion tract lengths. RESULTS: We apply the method to data from Drosophila melanogaster and D. yakuba. We find that pericentric inversions occur at a much lower rate compared to paracentric inversions. The average paracentric inversion tract length is approx. 4.8 Mb with small inversions being more frequent than large inversions. If the two breakpoints defining a paracentric inversion tract are uniformly and independently distributed over chromosome arms there will be more short tract-length inversions than long; we find an even greater preponderance of short tract lengths than this would predict. Thus there appears to be a correlation between the positions of breakpoints which favors shorter tract lengths. CONCLUSION: The method developed in this paper provides the first statistical estimator for estimating the distribution of inversion tract lengths from marker data. Application of this method for a number of data sets may help elucidate the relationship between the length of an inversion and the chance that it will get accepted.

Bayesian and maximum likelihood estimation of genetic maps.

There has recently been increased interest in the use of Markov Chain Monte Carlo (MCMC)-based Bayesian methods for estimating genetic maps. The advantage of these methods is that they can deal accurately with missing data and genotyping errors. Here we present an extension of the previous methods that makes the Bayesian method applicable to large data sets. We present an extensive simulation study examining the statistical properties of the method and comparing it with the likelihood method implemented in Mapmaker. We show that the Maximum A Posteriori (MAP) estimator of the genetic distances, corresponding to the maximum likelihood estimator, performs better than estimators based on the posterior expectation. We also show that while the performance is similar between Mapmaker and the MCMC-based method in the absence of genotyping errors, the MCMC-based method has a distinct advantage in the presence of genotyping errors. A similar advantage of the Bayesian method was not observed for missing data. We also re-analyse a recently published set of data from the eggplant and show that the use of the MCMC-based method leads to smaller estimates of genetic distances.

Comparative genome analyses of Arabidopsis spp.: inferring chromosomal rearrangement events in the evolutionary history of A. thaliana.

Comparative genome analysis is a powerful tool that can facilitate the reconstruction of the evolutionary history of the genomes of modern-day species. The model plant Arabidopsis thaliana with its n = 5 genome is thought to be derived from an ancestral n = 8 genome. Pairwise comparative genome analyses of A. thaliana with polyploid and diploid Brassicaceae species have suggested that rapid genome evolution, manifested by chromosomal rearrangements and duplications, characterizes the polyploid, but not the diploid, lineages of this family. In this study, we constructed a low-density genetic linkage map of Arabidopsis lyrata ssp. lyrata (A. l. lyrata; n = 8, diploid), the closest known relative of A. thaliana (MRCA approximately 5 Mya), using A. thaliana-specific markers that resolve into the expected eight linkage groups. We then performed comparative Bayesian analyses using raw mapping data from this study and from a Capsella study to infer the number and nature of rearrangements that distinguish the n = 8 genomes of A. l. lyrata and Capsella from the n = 5 genome of A. thaliana. We conclude that there is strong statistical support in favor of the parsimony scenarios of 10 major chromosomal rearrangements separating these n = 8 genomes from A. thaliana. These chromosomal rearrangement events contribute to a rate of chromosomal evolution higher than previously reported in this lineage. We infer that at least seven of these events, common to both sets of data, are responsible for the change in karyotype and underlie genome reduction in A. thaliana.

Bayesian estimation of genomic distance.

We present a Bayesian approach to the problem of inferring the number of inversions and translocations separating two species. The main reason for developing this method is that it will allow us to test hypotheses about the underlying mechanisms, such as the distribution of inversion track lengths or rate constancy among lineages. Here, we apply these methods to comparative maps of eggplant and tomato, human and cat, and human and cattle with 170, 269, and 422 markers, respectively. In the first case the most likely number of events is larger than the parsimony value. In the last two cases the parsimony solutions have very small probability.