Improved haplotype-based detection of ongoing selective sweeps towards an application in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>The increasing amount of genome information allows us to address various questions regarding the molecular evolution and population genetics of different species. Such genome-wide data sets including thousands of individuals genotyped at hundreds of thousands of markers require time-efficient and powerful analysis methods. Demography and sampling introduce a bias into present population genetic tests of natural selection, which may confound results. Thus, a modification of test statistics is necessary to introduce time-efficient and unbiased analysis methods.</p> <p>Results</p> <p>We present an improved haplotype-based test of selective sweeps in samples of unequally related individuals. For this purpose, we modified existing tests by weighting the contribution of each individual based on its uniqueness in the entire sample. In contrast to previous tests, this modified test is feasible even for large genome-wide data sets of multiple individuals. We utilize coalescent simulations to estimate the sensitivity of such haplotype-based test statistics to complex demographic scenarios, such as population structure, population growth and bottlenecks. The analysis of empirical data from humans reveals different results compared to previous tests. Additionally, we show that our statistic is applicable to empirical data from <it>Arabidopsis thaliana</it>. Overall, the modified test leads to a slight but significant increase of power to detect selective sweeps among all demographic scenarios.</p> <p>Conclusions</p> <p>The concept of this modification might be applied to other statistics in population genetics to reduce the intrinsic bias of demography and sampling. Additionally, the combination of different test statistics may further improve the performance of tests for natural selection.</p

A comparison of Gap statistic definitions with and without logarithm function

The Gap statistic is a standard method for determining the number of clusters in a set of data. The Gap statistic standardizes the graph of $\log(W_{k})$, where $W_{k}$ is the within-cluster dispersion, by comparing it to its expectation under an appropriate null reference distribution of the data. We suggest to use $W_{k}$ instead of $\log(W_{k})$, and to compare it to the expectation of $W_{k}$ under a null reference distribution. In fact, whenever a number fulfills the original Gap statistic inequality, this number also fulfills the inequality of a Gap statistic using $W_{k}$, but not \textit{vice versa}. The two definitions of the Gap function are evaluated on several simulated data sets and on a real data of DCE-MR images

Developmentally regulated expression, alternative splicing and distinct sub-groupings in members of the Schistosoma mansoni venom allergen-like (SmVAL) gene family

BACKGROUND: The Sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7 (SCP/TAPS) domain is found across phyla and is a major structural feature of insect allergens, mammalian sperm proteins and parasitic nematode secreted molecules. Proteins containing this domain are implicated in diverse biological activities and may be important for chronic host/parasite interactions. RESULTS: We report the first description of an SCP/TAPS gene family (Schistosoma mansoni venom allergen-like (SmVALs)) in the medically important Platyhelminthes (class Trematoda) and describe individual members' phylogenetic relationships, genomic organization and life cycle expression profiles. Twenty-eight SmVALs with complete SCP/TAPS domains were identified and comparison of their predicted protein features and gene structures indicated the presence of two distinct sub-families (group 1 & group 2). Phylogenetic analysis demonstrated that this group 1/group 2 split is zoologically widespread as it exists across the metazoan sub-kingdom. Chromosomal localisation and PCR analysis, coupled to inspection of the current S. mansoni genomic assembly, revealed that many of the SmVAL genes are spatially linked throughout the genome. Quantitative lifecycle expression profiling demonstrated distinct SmVAL expression patterns, including transcripts specifically associated with lifestages involved in definitive host invasion, transcripts restricted to lifestages involved in the invasion of the intermediate host and transcripts ubiquitously expressed. Analysis of SmVAL6 transcript diversity demonstrated statistically significant, developmentally regulated, alternative splicing. CONCLUSION: Our results highlight the existence of two distinct SCP/TAPS protein types within the Platyhelminthes and across taxa. The extensive lifecycle expression analysis indicates several SmVAL transcripts are upregulated in infective stages of the parasite, suggesting that these particular protein products may be linked to the establishment of chronic host/parasite interactions

The Superconductor-Insulator Transition in a Tunable Dissipative Environment

We study the influence of a tunable dissipative environment on the dynamics of Josephson junction arrays near the superconductor-insulator transition. The experimental realization of the environment is a two dimensional electron gas coupled capacitively to the array. This setup allows for the well-controlled tuning of the dissipation by changing the resistance of the two dimensional electron gas. The capacitive coupling cuts off the dissipation at low frequencies. We determine the phase diagram and calculate the temperature and dissipation dependence of the array conductivity. We find good agreement with recent experimental results.Comment: 4 pages, 4 .eps figures, revte

Single feature polymorphism (SFP)-based selective sweep identification and association mapping of growth-related metabolic traits in Arabidopsis thaliana

Background: Natural accessions of Arabidopsis thaliana are characterized by a high level of phenotypic variation that can be used to investigate the extent and mode of selection on the primary metabolic traits. A collection of 54 A. thaliana natural accession-derived lines were subjected to deep genotyping through Single Feature Polymorphism (SFP) detection via genomic DNA hybridization to Arabidopsis Tiling 1.0 Arrays for the detection of selective sweeps, and identification of associations between sweep regions and growth-related metabolic traits. Results: A total of 1,072,557 high-quality SFPs were detected and indications for 3,943 deletions and 1,007 duplications were obtained. A significantly lower than expected SFP frequency was observed in protein-, rRNA-, and tRNA-coding regions and in non-repetitive intergenic regions, while pseudogenes, transposons, and non-coding RNA genes are enriched with SFPs. Gene families involved in plant defence or in signalling were identified as highly polymorphic, while several other families including transcription factors are depleted of SFPs. 198 significant associations between metabolic genes and 9 metabolic and growth-related phenotypic traits were detected with annotation hinting at the nature of the relationship. Five significant selective sweep regions were also detected of which one associated significantly with a metabolic trait. Conclusions: We generated a high density polymorphism map for 54 A. thaliana accessions that highlights the variability of resistance genes across geographic ranges and used it to identify selective sweeps and associations between metabolic genes and metabolic phenotypes. Several associations show a clear biological relationship, while many remain requiring further investigation

Post-mortem magnetic resonance imaging with computed tomography-guided biopsy for foetuses and infants: a prospective, multicentre, cross-sectional study

BACKGROUND: Post-mortem imaging has been suggested as an alternative to conventional autopsy in the prenatal and postnatal periods. Noninvasive autopsies do not provide tissue for histological examination, which may limit their clinical value, especially when infection-related morbidity and mortality are suspected. METHODS: We performed a prospective, multicentre, cross-sectional study to compare the diagnostic performance of post-mortem magnetic resonance imaging with computed tomography-guided biopsy (Virtopsy®) with that of conventional autopsy in foetuses and infants. Cases referred for conventional autopsy were eligible for enrolment. After post-mortem imaging using a computed tomography scanner and a magnetic resonance imaging unit, computed tomography-guided tissue sampling was performed. Virtopsy results were compared with conventional autopsy in determining the likely final cause of death and major pathologies. The primary outcome was the proportion of cases for which the same cause of death was determined by both methods. Secondary outcomes included the proportion of false positive and false negative major pathological lesions detected by virtopsy and the proportion of computed tomography-guided biopsies that were adequate for histological examination. RESULTS: Overall, 101 cases (84 fetuses, 17 infants) were included. Virtopsy and autopsy identified the same cause of death in 91 cases (90.1%, 95% CI 82.7 to 94.5). The sensitivity and specificity of virtopsy for determining the cause of death were 96.6% (95% CI 90.6 to 98.8) and 41.7% (95% CI 19.3 to 68.0), respectively. In 32 cases (31.7%, 95% CI 23.4 to 41.3), major pathological findings remained undetected by virtopsy, and in 45 cases (44.6%, 95% CI 35.2 to 54.3), abnormalities were diagnosed by virtopsy but not confirmed by autopsy. Computed tomography-guided tissue sampling was adequate for pathological comments in 506 of 956 biopsies (52.7%) and added important diagnostic value in five of 30 cases (16.1%) with an unclear cause of death before autopsy compared with postmortem imaging alone. In 19 of 20 infective deaths (95%), biopsies revealed infection-related tissue changes. Infection was confirmed by placental examination in all fetal cases. CONCLUSIONS: Virtopsy demonstrated a high concordance with conventional autopsy for the detection of cause of death but was less accurate for the evaluation of major pathologies. Computed tomography-guided biopsy had limited additional diagnostic value. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01888380)

Clostridium difficile ribotypes in Austria: a multicenter, hospital-based survey

A prospective, noninterventional survey was conducted among Clostridium difficile positive patients identified in the time period of July until October 2012 in 18 hospitals distributed across all nine Austrian provinces. Participating hospitals were asked to send stool samples or isolates from ten successive patients with C.difficile infection to the National Clostridium difficile Reference Laboratory at the Austrian Agency for Health and Food Safety for PCR-ribotyping and in vitro susceptibility testing. A total of 171 eligible patients were identified, including 73 patients with toxin-positive stool specimens and 98 patients from which C. difficile isolates were provided. Of the 159 patients with known age, 127 (74.3 %) were 65 years or older, the median age was 76 years (range: 9–97 years), and the male to female ratio 2.2. Among these patients, 73 % had health care-associated and 20 % community-acquired C. difficile infection (indeterminable 7 %). The all-cause, 30-day mortality was 8.8 % (15/171). Stool samples yielded 46 different PCR-ribotypes, of which ribotypes 027 (20 %), 014 (15.8 %), 053 (10.5 %), 078 (5.3 %), and 002 (4.7 %) were the five most prevalent. Ribotype 027 was found only in the provinces Vienna, Burgenland, and Lower Austria. Severe outcome of C. difficile infection was found to be associated with ribotype 053 (prevalence ratio: 3.04; 95 % CI: 1.24, 7.44), not with the so-called hypervirulent ribotypes 027 and 078. All 027 and 053 isolates exhibited in vitro resistance against moxifloxacin. Fluoroquinolone use in the health care setting must be considered as a factor favoring the spread of these fluoroquinolone resistant C. difficile clones

Exome sequencing of geographically diverse barley landraces and wild relatives gives insights into environmental adaptation

After domestication, during a process of widespread range extension, barley adapted to a broad spectrum of agricultural environments. To explore how the barley genome responded to the environmental challenges it encountered, we sequenced the exomes of a collection of 267 georeferenced landraces and wild accessions. A combination of genome-wide analyses showed that patterns of variation have been strongly shaped by geography and that variant-by-environment associations for individual genes are prominent in our data set. We observed significant correlations of days to heading (flowering) and height with seasonal temperature and dryness variables in common garden experiments, suggesting that these traits were major drivers of environmental adaptation in the sampled germplasm. A detailed analysis of known flowering-associated genes showed that many contain extensive sequence variation and that patterns of single- and multiple-gene haplotypes exhibit strong geographical structuring. This variation appears to have substantially contributed to range-wide ecogeographical adaptation, but many factors key to regional success remain unidentified.</p