Automatic Classification of Full- and Reduced-Lead Electrocardiograms Using Morphological Feature Extraction

Cardiovascular diseases are the global leading cause of death. Automated electrocardiogram (ECG) analysis can support clinicians to identify abnormal excitation of the heart and prevent premature cardiovascular death. An explainable classification is particularly important for support systems. Our contribution to the PhysioNet/CinC Challenge 2021 (team name: ibmtPeakyFinders) therefore pursues an approach that is based on interpretable features to be as explainable as possible. To meet the challenge goal of developing an algorithm that works for both 12-lead and reduced lead ECGs, we processed each lead separately. We focused on signal processing techniques based on template delineation that yield the template's fiducial points to take the ECG waveform morphology into account. In addition to beat intervals and amplitudes obtained from the template, various heart rate variability and QT interval variability features were extracted and supplemented by signal quality indices. Our classification approach utilized a decision tree ensemble in a one-vs-rest approach. The model parameters were determined using an extensive grid search. Our approach achieved challenge scores of 0.47, 0.47, 0.34, 0.40, and 0.41 on hidden 12-, 6-, 4-, 3-, and 2-lead test sets, respectively, which corresponds to the ranks 12, 10, 23, 18, and 16 out of 39 teams

Evolutionary conservation-evaluating the adaptive potential of species

Despite intense efforts, biodiversity around the globe continues to decrease. To cease this phenomenon, we urgently need a better knowledge not only of the true extent of biodiversity, but also of the evolutionary potential of species to respond to environmental change. These aims are the heart of the developing field of Evolutionary conservation. Here, after describing problems associated with implementing evolutionary perspectives into management, we outline how evolutionary principles can contribute to efficient conservation programmes. We then introduce articles from this special issue on Evolutionary conservation, outlining how each study or review provides tools and concepts to contribute to efficient management of species or populations. Ultimately, we highlight what we believe can be future research avenues for evolutionary conservation

Disentangling synergistic disease dynamics: Implications for the viral biocontrol of rabbits

European rabbits (Oryctolagus cuniculus) have been exposed to rabbit haemorrhagic disease virus (RHDV) and myxoma virus (MYXV) in their native and invasive ranges for decades. Yet, the long‐term effects of these viruses on rabbit population dynamics remain poorly understood.In this context, we analysed 17 years of detailed capture–mark–recapture data (2000–2016) from Turretfield, South Australia, using a probabilistic state‐space hierarchical modelling framework to estimate rabbit survival and epidemiological dynamics.While RHDV infection and disease‐induced death were most prominent during annual epidemics in winter and spring, we found evidence for continuous infection of susceptible individuals with RHDV throughout the year. RHDV‐susceptible rabbits had, on average, 25% lower monthly survival rates compared to immune individuals, while the average monthly force of infection in winter and spring was ∼38%. These combined to result in an average infection‐induced mortality rate of 69% in winter and spring.Individuals susceptible to MYXV and immune to RHDV had similar survival probabilities to those having survived infections from both viruses, whereas individuals susceptible to both RHDV and MYXV had higher survival probabilities than those susceptible to RHDV and immune to MYXV. This suggests that MYXV may reduce the future survival rates of individuals that endure initial MYXV infection.There was no evidence for long‐term changes in disease‐induced mortality and infection rates for either RHDV or MYXV.We conclude that continuous, year‐round virus perpetuation (and perhaps heterogeneity in modes of transmission and infectious doses during and after epidemics) acts to reduce the efficiency of RHDV and MYXV as biocontrol agents of rabbits in their invasive range. However, if virulence can be maintained as relatively constant through time, RHDV and MYXV will likely continue realizing strong benefits as biocontrol agents

Immunogenetic novelty confers a selective advantage in host–pathogen coevolution

The major histocompatibility complex (MHC) is crucial to the adaptive immune response of vertebrates and is among the most polymorphic gene families known. Its high diversity is usually attributed to selection imposed by fast-evolving pathogens. Pathogens are thought to evolve to escape recognition by common immune alleles, and, hence, novel MHC alleles, introduced through mutation, recombination, or gene flow, are predicted to give hosts superior resistance. Although this theoretical prediction underpins host–pathogen “Red Queen” coevolution, it has not been demonstrated in the context of natural MHC diversity. Here, we experimentally tested whether novel MHC variants (both alleles and functional “supertypes”) increased resistance of guppies (Poecilia reticulata) to a common ectoparasite (Gyrodactylus turnbulli). We used exposure-controlled infection trials with wild-sourced parasites, and Gyrodactylus-naïve host fish that were F2 descendants of crossed wild populations. Hosts carrying MHC variants (alleles or supertypes) that were new to a given parasite population experienced a 35–37% reduction in infection intensity, but the number of MHC variants carried by an individual, analogous to heterozygosity in single-locus systems, was not a significant predictor. Our results provide direct evidence of novel MHC variant advantage, confirming a fundamental mechanism underpinning the exceptional polymorphism of this gene family and highlighting the role of immunogenetic novelty in host–pathogen coevolution

The hidden benefits of sex: Evidence for MHC-associated mate choice in primate societies

Major histocompatibility complex (MHC)-associated mate choice is thought to give offspring a fitness advantage through disease resistance. Primates offer a unique opportunity to understand MHC-associated mate choice within our own zoological order, while their social diversity provides an exceptional setting to examine the genetic determinants and consequences of mate choice in animal societies. Although mate choice is constrained by social context, increasing evidence shows that MHC-dependent mate choice occurs across the order in a variety of socio-sexual systems and favours mates with dissimilar, diverse or specific genotypes non-exclusively. Recent research has also identified phenotypic indicators of MHC quality. Moreover, novel findings rehabilitate the importance of olfactory cues in signalling MHC genes and influencing primate mating decisions. These findings underline the importance to females of selecting a sexual partner of high genetic quality, as well as the generality of the role of MHC genes in sexual selection

Does Genetic Diversity Predict Health in Humans?

Genetic diversity, especially at genes important for immune functioning within the Major Histocompatibility Complex (MHC), has been associated with fitness-related traits, including disease resistance, in many species. Recently, genetic diversity has been associated with mate preferences in humans. Here we asked whether these preferences are adaptive in terms of obtaining healthier mates. We investigated whether genetic diversity (heterozygosity and standardized mean d2) at MHC and nonMHC microsatellite loci, predicted health in 153 individuals. Individuals with greater allelic diversity (d2) at nonMHC loci and at one MHC locus, linked to HLA-DRB1, reported fewer symptoms over a four-month period than individuals with lower d2. In contrast, there were no associations between MHC or nonMHC heterozygosity and health. NonMHC-d2 has previously been found to predict male preferences for female faces. Thus, the current findings suggest that nonMHC diversity may play a role in both natural and sexual selection acting on human populations

Insights into the Complex Associations Between MHC Class II DRB Polymorphism and Multiple Gastrointestinal Parasite Infestations in the Striped Mouse

Differences in host susceptibility to different parasite types are largely based on the degree of matching between immune genes and parasite antigens. Specifically the variable genes of the major histocompatibility complex (MHC) play a major role in the defence of parasites. However, underlying genetic mechanisms in wild populations are still not well understood because there is a lack of studies which deal with multiple parasite infections and their competition within. To gain insights into these complex associations, we implemented the full record of gastrointestinal nematodes from 439 genotyped individuals of the striped mouse, Rhabdomys pumilio. We used two different multivariate approaches to test for associations between MHC class II DRB genotype and multiple nematodes with regard to the main pathogen-driven selection hypotheses maintaining MHC diversity and parasite species-specific co-evolutionary effects. The former includes investigations of a ‘heterozygote advantage’, or its specific form a ‘divergent-allele advantage’ caused by highly dissimilar alleles as well as possible effects of specific MHC-alleles selected by a ‘rare allele advantage’ ( = negative ‘frequency-dependent selection’). A combination of generalized linear mixed models (GLMMs) and co-inertia (COIA) analyses made it possible to consider multiple parasite species despite the risk of type I errors on the population and on the individual level. We could not find any evidence for a ‘heterozygote’ advantage but support for ‘divergent-allele’ advantage and infection intensity. In addition, both approaches demonstrated high concordance of positive as well as negative associations between specific MHC alleles and certain parasite species. Furthermore, certain MHC alleles were associated with more than one parasite species, suggesting a many-to-many gene-parasite co-evolution. The most frequent allele Rhpu-DRB*38 revealed a pleiotropic effect, involving three nematode species. Our study demonstrates the co-existence of specialist and generalist MHC alleles in terms of parasite detection which may be an important feature in the maintenance of MHC polymorphism

Identification, characterisation and expression analysis of natural killer receptor genes in Chlamydia pecorum infected koalas (Phascolarctos cinereus)

BACKGROUND: Koalas (Phascolarctos cinereus), an iconic Australian marsupial, are being heavily impacted by the spread of Chlamydia pecorum, an obligate intracellular bacterial pathogen. Koalas vary in their response to this pathogen, with some showing no symptoms, while others suffer severe symptoms leading to infertility, blindness or death. Little is known about the pathology of this disease and the immune response against it in this host. Studies have demonstrated that natural killer (NK) cells, key components of the innate immune system, are involved in the immune response to chlamydial infections in humans. These cells can directly lyse cells infected by intracellular pathogens and their ability to recognise these infected cells is mediated through NK receptors on their surface. These are encoded in two regions of the genome, the leukocyte receptor complex (LRC) and the natural killer complex (NKC). These two families evolve rapidly and different repertoires of genes, which have evolved by gene duplication, are seen in different species. METHODS: In this study we aimed to characterise genes belonging to the NK receptor clusters in the koala by searching available koala transcriptomes using a combination of search methods. We developed a qPCR assay to quantify relative expression of four genes, two encoded within the NK receptor cluster (CLEC1B, CLEC4E) and two known to play a role in NK response to Chalmydia in humans (NCR3, PRF1). RESULTS: We found that the NK receptor repertoire of the koala closely resembles that of the Tasmanian devil, with minimal genes in the NKC, but with lineage specific expansions in the LRC. Additional genes important for NK cell activity, NCR3 and PRF1, were also identified and characterised. In a preliminary study to investigate whether these genes are involved in the koala immune response to infection by its chlamydial pathogen, C. pecorum, we investigated the expression of four genes in koalas with active chlamydia infection, those with past infection and those without infection using qPCR. This analysis revealed that one of these four, CLEC4E, may be upregulated in response to chlamydia infection. CONCLUSION: We have characterised genes of the NKC and LRC in koalas and have discovered evidence that one of these genes may be upregulated in koalas with chlamydia, suggesting that these receptors may play a role in the immune response of koalas to chlamydia infection

Characterization of Major Histocompatibility Complex (MHC) DRB Exon 2 and DRA Exon 3 Fragments in a Primary Terrestrial Rabies Vector (Procyon lotor)

The major histocompatibility complex (MHC) presents a unique system to explore links between genetic diversity and pathogens, as diversity within MHC is maintained in part by pathogen driven selection. While the majority of wildlife MHC studies have investigated species that are of conservation concern, here we characterize MHC variation in a common and broadly distributed species, the North American raccoon (Procyon lotor). Raccoons host an array of broadly distributed wildlife diseases (e.g., canine distemper, parvovirus and raccoon rabies virus) and present important human health risks as they persist in high densities and in close proximity to humans and livestock. To further explore how genetic variation influences the spread and maintenance of disease in raccoons we characterized a fragment of MHC class II DRA exon 3 (250bp) and DRB exon 2 (228 bp). MHC DRA was found to be functionally monomorphic in the 32 individuals screened; whereas DRB exon 2 revealed 66 unique alleles among the 246 individuals screened. Between two and four alleles were observed in each individual suggesting we were amplifying a duplicated DRB locus. Nucleotide differences between DRB alleles ranged from 1 to 36 bp (0.4–15.8% divergence) and translated into 1 to 21 (1.3–27.6% divergence) amino acid differences. We detected a significant excess of nonsynonymous substitutions at the peptide binding region (P = 0.005), indicating that DRB exon 2 in raccoons has been influenced by positive selection. These data will form the basis of continued analyses into the spatial and temporal relationship of the raccoon rabies virus and the immunogenetic response in its primary host