This paper presents a multi-temporal underwater photogrammetric survey of a reef patch located in Moorea, French Polynesia, designed to detect a coral growth of 10–15 mm/year. Structure-from-Motion ...photogrammetry and underwater imagery allows the three-dimensional quantification of reef structural complexity and ecologically relevant characteristics at the patch scale. A high degree of accuracy and fine resolution are required in order to guarantee the repeatability of surveys over time within the same reference system, meaning a proper geodetic network and acquisition scheme are mandatory. Measuring tools and reference points were properly designed in order to constrain the photogrammetric reconstruction. The network adjustment, performed with distance and height difference observations, provided an average accuracy of ± 1.2 mm and ± 2.9 mm in the horizontal and vertical components, respectively. The final accuracies of photogrammetric reconstructions are on the order of 1 cm and few millimeters for the 2017 and 2018 monitoring campaigns, respectively. This results in realized errors in the comparison of about ± 1 cm. Coordinate variations larger than this magnitude can be reasonably interpreted as coral growth or dissolution. The direct comparison of the two subsequent point clouds is effective in order to evaluate trends in growth and perform morphometric analyses. For highly accurate quantitative assessment of local changes, an expert operator can create and analyze specific 2D profiles that are easily produced from the point clouds.
Non-protein-coding genetic variants are a major driver of the genetic risk for human disease; however, identifying which non-coding variants contribute to diseases and their mechanisms remains ...challenging. In silico variant prioritization methods quantify a variant’s severity, but for most methods, the specific phenotype and disease context of the prediction remain poorly defined. For example, many commonly used methods provide a single, organism-wide score for each variant, while other methods summarize a variant’s impact in certain tissues and/or cell types. Here, we propose a complementary disease-specific variant prioritization scheme, which is motivated by the observation that variants contributing to disease often operate through specific biological mechanisms. We combine tissue/cell-type-specific variant scores (e.g., GenoSkyline, FitCons2, DNA accessibility) into disease-specific scores with a logistic regression approach and apply it to ∼25,000 non-coding variants spanning 111 diseases. We show that this disease-specific aggregation significantly improves the association of common non-coding genetic variants with disease (average precision: 0.151, baseline = 0.09), compared with organism-wide scores (GenoCanyon, LINSIGHT, GWAVA, Eigen, CADD; average precision: 0.129, baseline = 0.09). Further on, disease similarities based on data-driven aggregation weights highlight meaningful disease groups, and it provides information about tissues and cell types that drive these similarities. We also show that so-learned similarities are complementary to genetic similarities as quantified by genetic correlation. Overall, our approach demonstrates the strengths of disease-specific variant prioritization, leads to improvement in non-coding variant prioritization, and enables interpretable models that link variants to disease via specific tissues and/or cell types.
Non-coding genetic variants constitute the majority of disease-associated genetic variation in humans. In this study, Liang et al. show that variant prioritization within a specific disease context improves performance and that it enables the linking of variants to disease via specific tissues and cell types.
Identifying pregnancies at risk for preterm birth, one of the leading causes of worldwide infant mortality, has the potential to improve prenatal care. However, we lack broadly applicable methods to ...accurately predict preterm birth risk. The dense longitudinal information present in electronic health records (EHRs) is enabling scalable and cost-efficient risk modeling of many diseases, but EHR resources have been largely untapped in the study of pregnancy.
Here, we apply machine learning to diverse data from EHRs with 35,282 deliveries to predict singleton preterm birth.
We find that machine learning models based on billing codes alone can predict preterm birth risk at various gestational ages (e.g., ROC-AUC = 0.75, PR-AUC = 0.40 at 28 weeks of gestation) and outperform comparable models trained using known risk factors (e.g., ROC-AUC = 0.65, PR-AUC = 0.25 at 28 weeks). Examining the patterns learned by the model reveals it stratifies deliveries into interpretable groups, including high-risk preterm birth subtypes enriched for distinct comorbidities. Our machine learning approach also predicts preterm birth subtypes (spontaneous vs. indicated), mode of delivery, and recurrent preterm birth. Finally, we demonstrate the portability of our approach by showing that the prediction models maintain their accuracy on a large, independent cohort (5978 deliveries) from a different healthcare system.
By leveraging rich phenotypic and genetic features derived from EHRs, we suggest that machine learning algorithms have great potential to improve medical care during pregnancy. However, further work is needed before these models can be applied in clinical settings.
Long-term balancing selection (LTBS) can maintain allelic variation at a locus over millions of years and through speciation events. Variants shared between species in the state of ...identity-by-descent, hereafter "trans-species polymorphisms", can result from LTBS, often due to host-pathogen interactions. For instance, the major histocompatibility complex (MHC) locus contains TSPs present across primates. Several hundred candidate LTBS regions have been identified in humans and chimpanzees; however, because many are in non-protein-coding regions of the genome, the functions and potential adaptive roles for most remain unknown.
We integrated diverse genomic annotations to explore the functions of 60 previously identified regions with multiple shared polymorphisms (SPs) between humans and chimpanzees, including 19 with strong evidence of LTBS. We analyzed genome-wide functional assays, expression quantitative trait loci (eQTL), genome-wide association studies (GWAS), and phenome-wide association studies (PheWAS) for all the regions. We identify functional annotations for 59 regions, including 58 with evidence of gene regulatory function from GTEx or functional genomics data and 19 with evidence of trait association from GWAS or PheWAS. As expected, the SPs associate in humans with many immune system phenotypes, including response to pathogens, but we also find associations with a range of other phenotypes, including body size, alcohol intake, cognitive performance, risk-taking behavior, and urate levels.
The diversity of traits associated with non-coding regions with multiple SPs support previous hypotheses that functions beyond the immune system are likely subject to LTBS. Furthermore, several of these trait associations provide support and candidate genetic loci for previous hypothesis about behavioral diversity in human and chimpanzee populations, such as the importance of variation in risk sensitivity.
Evolutionary changes in enhancers are widely associated with variation in human traits and diseases. However, studies comprehensively quantifying levels of selection on enhancers at multiple ...evolutionary periods during recent human evolution and how enhancer evolution varies across human tissues are lacking. To address these questions, we integrated a dataset of 41,561 transcribed enhancers active in 41 different human tissues (FANTOM Consortium) with whole genome sequences of 1,668 individuals from the African, Asian, and European populations (1000 Genomes Project). Our analyses based on four different metrics (Tajima's
,
, H12,
) showed that ∼5.90% of enhancers showed evidence of recent positive selection and that genes associated with enhancers under very recent positive selection are enriched for diverse immune-related functions. The distributions of these metrics for brain and testis enhancers were often statistically significantly different and in the direction suggestive of less positive selection compared to those of other tissues; the same was true for brain and testis enhancers that are tissue-specific compared to those that are tissue-broad and for testis enhancers associated with tissue-enriched and non-tissue-enriched genes. These differences varied considerably across metrics and tissues and were generally in the form of changes in distributions' shapes rather than shifts in their values. Collectively, these results suggest that many human enhancers experienced recent positive selection throughout multiple time periods in human evolutionary history, that this selection occurred in a tissue-dependent and immune-related functional context, and that much like the evolution of their protein-coding gene counterparts, the evolution of brain and testis enhancers has been markedly different from that of enhancers in other tissues.
In recent decades a general change in climate has been documented in several locations over the world. Such changes could have significant effects on various environmental scenarios, including water ...resource management, agriculture, hydrology and ecosystems. The complex topography and coastlines of Mediterranean regions influences the climatic regime exhibiting substantial fine-scale spatial variability. In Italy, the climate is generally becoming warmer and drier, with quite large differences depending on the site and data treatment. In this study a historical set of meteorological data (110 precipitation and 28 temperature series), collected over 1921–2007 in the Calabria region (Southern Italy) was analysed. Several meteorological and agrometeorological indices were selected for whether they could evaluate the potential effects of climate change on water availability for natural vegetation and cultivated plants. The significance of the analysed time series (monthly, seasonal and annual time scales) was evaluated by using statistical trend analysis (Mann-Kendall and
t
-test). Moreover, the intensities of drought events were determined using the Standardized Precipitation Index (SPI) for the time scales of 3 and 6 months. The analysis highlighted a general decrease in annual precipitation and an increase in drought intensity. At a regional level, yearly precipitation decreased by almost 318 mm/100 years (representing almost 30 % of the yearly mean precipitation in the region). Temperature changes were more complex. On a regional scale, yearly mean minimum temperatures increased by 0.9 °C/100 years and maximum and mean temperatures decreased by 1 °C/100 years and 0.8 °C/100 years, respectively. Due to the asymmetric behaviour of temperatures, there was a decreasing impact on evapotranspiration.
Physicists have long wondered whether the gravitational interactions between matter and antimatter might be different from those between matter and itself. Although there are many indirect ...indications that no such differences exist and that the weak equivalence principle holds, there have been no direct, free-fall style, experimental tests of gravity on antimatter. Here we describe a novel direct test methodology; we search for a propensity for antihydrogen atoms to fall downward when released from the ALPHA antihydrogen trap. In the absence of systematic errors, we can reject ratios of the gravitational to inertial mass of antihydrogen >75 at a statistical significance level of 5%; worst-case systematic errors increase the minimum rejection ratio to 110. A similar search places somewhat tighter bounds on a negative gravitational mass, that is, on antigravity. This methodology, coupled with ongoing experimental improvements, should allow us to bound the ratio within the more interesting near equivalence regime.
Antihydrogen, a positron bound to an antiproton, is the simplest anti-atom. Its structure and properties are expected to mirror those of the hydrogen atom. Prospects for precision comparisons of the ...two, as tests of fundamental symmetries, are driving a vibrant programme of research. In this regard, a limiting factor in most experiments is the availability of large numbers of cold ground state antihydrogen atoms. Here, we describe how an improved synthesis process results in a maximum rate of 10.5 ± 0.6 atoms trapped and detected per cycle, corresponding to more than an order of magnitude improvement over previous work. Additionally, we demonstrate how detailed control of electron, positron and antiproton plasmas enables repeated formation and trapping of antihydrogen atoms, with the simultaneous retention of atoms produced in previous cycles. We report a record of 54 detected annihilation events from a single release of the trapped anti-atoms accumulated from five consecutive cycles.Antihydrogen studies are important in testing the fundamental principles of physics but producing antihydrogen in large amounts is challenging. Here the authors demonstrate an efficient and high-precision method for trapping and stacking antihydrogen by using controlled plasma.
KCNE1 encodes a 129-residue cardiac potassium channel (I
) subunit. KCNE1 variants are associated with long QT syndrome and atrial fibrillation. However, most variants have insufficient evidence of ...clinical consequences and thus limited clinical utility.
In this study, we leveraged the power of variant effect mapping, which couples saturation mutagenesis with high-throughput sequencing, to ascertain the function of thousands of protein-coding KCNE1 variants.
We comprehensively assayed KCNE1 variant cell surface expression (2554/2709 possible single-amino-acid variants) and function (2534 variants). Our study identified 470 loss- or partial loss-of-surface expression and 574 loss- or partial loss-of-function variants. Of the 574 loss- or partial loss-of-function variants, 152 (26.5%) had reduced cell surface expression, indicating that most functionally deleterious variants affect channel gating. Nonsense variants at residues 56-104 generally had WT-like trafficking scores but decreased functional scores, indicating that the latter half of the protein is dispensable for protein trafficking but essential for channel function. 22 of the 30 KCNE1 residues (73%) highly intolerant of variation (with > 70% loss-of-function variants) were in predicted close contact with binding partners KCNQ1 or calmodulin. Our functional assay data were consistent with gold standard electrophysiological data (ρ = - 0.64), population and patient cohorts (32/38 presumed benign or pathogenic variants with consistent scores), and computational predictors (ρ = - 0.62). Our data provide moderate-strength evidence for the American College of Medical Genetics/Association of Molecular Pathology functional criteria for benign and pathogenic variants.
Comprehensive variant effect maps of KCNE1 can both provide insight into I
channel biology and help reclassify variants of uncertain significance.
The positron, the antiparticle of the electron, predicted by Dirac in 1931 and discovered by Anderson in 1933, plays a key role in many scientific and everyday endeavours. Notably, the positron is a ...constituent of antihydrogen, the only long-lived neutral antimatter bound state that can currently be synthesized at low energy, presenting a prominent system for testing fundamental symmetries with high precision. Here, we report on the use of laser cooled Be
ions to sympathetically cool a large and dense plasma of positrons to directly measured temperatures below 7 K in a Penning trap for antihydrogen synthesis. This will likely herald a significant increase in the amount of antihydrogen available for experimentation, thus facilitating further improvements in studies of fundamental symmetries.
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