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Background

The American College of Medical Genetics and American College of Pathologists (ACMG/AMP) variant classification guidelines for clinical reporting are widely used in diagnostic laboratories for variant interpretation. The ACMG/AMP guidelines recommend complete concordance of predictions among all in silico algorithms used without specifying the number or types of algorithms. The subjective nature of this recommendation contributes to discordance of variant classification among clinical laboratories and prevents definitive classification of variants.

Results

Using 14,819 benign or pathogenic missense variants from the ClinVar database, we compared performance of 25 algorithms across datasets differing in distinct biological and technical variables. There was wide variability in concordance among different combinations of algorithms with particularly low concordance for benign variants. We also identify a previously unreported source of error in variant interpretation (false concordance) where concordant in silico predictions are opposite to the evidence provided by other sources. We identified recently developed algorithms with high predictive power and robust to variables such as disease mechanism, gene constraint, and mode of inheritance, although poorer performing algorithms are more frequently used based on review of the clinical genetics literature (2011–2017).

Conclusions

Our analyses identify algorithms with high performance characteristics independent of underlying disease mechanisms. We describe combinations of algorithms with increased concordance that should improve in silico algorithm usage during assessment of clinically relevant variants using the ACMG/AMP guidelines.
  相似文献   
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Resource allocation trade-offs between sexual functions are predicted, but these are usually measured only at the whole plant level. In some gynodioecious species, individuals with partially restored male fertility exist providing an opportunity to investigate whether the costs associated with male fertility restoration are linked to seed production. In this study, we examined whether there is a relationship between the numbers of stamens and seeds produced both at the flower level and at the plant level in the gynodioecious herb Geranium sylvaticum. We individually marked flowers in plants varying in the degree of male sterility in the field and counted the number of seeds produced. There was no significant correlation between the numbers of stamens and seeds produced at the flower level suggesting an absence of resource trade-off between female and male functions. Furthermore, the numbers of stamens and seeds were positively correlated at the plant level. The lack of trade-offs between the two sexual functions in this species indicates that relative sex allocation was not affected by resources within a single season and/or that the male costs were relatively small.  相似文献   
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The Paraguayan territory and region, in the centre of South America, is a huge transition area with a succession of various vegetation types. However, this area has received little attention from researchers, with few works published on its flora and its delimitations. We aimed to identify the most important environmental driving forces and delimit floristic patterns in this region, since understanding the forces that drive floristic variations in this ecotonal region could help comprehend the distribution of vegetation not only in this region but throughout South America. We obtained 1234 tree species occurrence records, 205 geographic coordinates and 23 environmental variables and altitude from the ‘NeoTropTree’ database and verified the influence and contribution of environmental factors through variance partition. We tested the floristic consistency of the different vegetation types using dendrogram, indicator species and ordination analyses. We also constructed multiple linear models to check the correlation between species distribution and environmental variables. We found eight consistent vegetation types. The spatial variables coupled with environmental variables were more important than individual environmental or spatial variables. Among the environmental variables, the aridity index was the most important. Despite the importance of spatial factors, due to environmental heterogeneity, we found a gradient related to climate and edaphic variables related to tree flora. The results confirm that the Paraguayan territory and region can be considered to be a diversified and important ecotone area in South America with respect to tree flora.  相似文献   
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We aim to unravel the biogeographic structuring of western Palaearctic longhorn beetles with focus on the location of different refugia, barriers to dispersal and postglacial range expansions with their particular filters. The interaction of different ecological features with these structures is analysed. The western Palaearctic was divided into 95 geographic entities. We produced presence-only matrices for all 955 Cerambycoidea species autochthonous to this area and derived species richness distributions and extracted faunal regions and faunal elements by cluster analyses and principal component analyses. Similar analyses were performed for sub-families and ecological groups. Longhorn beetles show a strong biogeographic structuring in the western Palaearctic. Species numbers strongly decrease to the north and west. Less mobile species and root feeders mostly contribute to the fauna of the Mediterranean region, whilst mobile species are more widespread. Feeders on broad-leaved trees dominate in western Europe, whilst feeders on coniferous trees are most important in northern Europe. Our results support multiple refugia in the Mediterranean region and underline the importance of Provence, Crimea and Crete as such refugia. Crete even might be an area of old endemism. The Atlanto- and the Ponto-Mediterranean regions are more strongly structured than assumed in classical biogeography. Mediterranean assemblages are mostly composed of non-flying species, root feeders and species with small distributions not found outside their glacial refugia. Tree feeders left their glacial retreats with their host plants. These range dynamics result in biogeographic structures with several dispersal barriers and filters composed of mountains, sea straits and climatic conditions.  相似文献   
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The claustrum in Cnidaria is a tissue in the gastrovascular cavity delimited by a central layer of mesoglea surrounded by gastrodermis (i.e., gastrodermis-mesoglea-gastrodermis), without communication with epidermis. By dividing the gastrovascular cavity, the four claustra provide an additional level of complexity. The presence of claustra in Cubozoa and Staurozoa has been used as evidence supporting a close relationship between these two cnidarian classes. However, the detailed anatomy of the claustrum has never been comparatively analyzed, rendering the evolution of this character among Cnidaria and its homology in Staurozoa and Cubozoa uncertain. This study provides a comparative investigation of the internal anatomy of the claustrum in Staurozoa and Cubozoa, addressing its evolutionary history based on recent phylogenetic hypotheses for Cnidaria. We conclude that the claustrum is a character exclusive to some species of Staurozoa, with a homoplastic evolution in the class, and that the structure called the “claustrum” in Cubozoa corresponds to the valve of gastric ostium, a structure at the base of the manubrium, which is also present in Staurozoa with and without claustrum. Thus, the claustrum cannot be a synapomorphy of a hypothetical clade uniting Staurozoa and Cubozoa, nor can its hypothetical presence in enigmatic fossils be used to support cubozoan affinities.  相似文献   
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In order to identify the lower limb movements accurately and quickly, a recognition method based on extreme learning machine (ELM) is proposed. The recognizing target set is constructed by decomposing the daily actions into different segments. To get the recognition accuracy of seven movements based on the surface electromyography, the recognition feature vector space is established by integrating short-time statistical characteristics under time domain, and locally linear embedding algorithm is used to reduce the computational complexity and improve robustness of algorithm. Compared with BP, the overall recognition accuracy for each subject in the best dimension with ELM is above 95%.  相似文献   
9.
Pericytes are CD146+ perivascular cells (PCs) that have multipotential differentiation capacity as mesenchymal stem cells. Beside their crucial roles in vascular development and blood flow regulation, they have ability to differentiate into vascular cell types in vivo. These properties make pericytes preferred cells in the field of vascular tissue engineering. Culture medium for in vitro differentiation of pericytes to vascular smooth muscle cells (SMCs) has not been defined yet. The aim of this study is to try different culture media for SMC differentiation of CD146+ PCs. For this purpose, CD146+ PCs were isolated from human umbilical cord vein. Then they were characterized by immunofluorescence staining and flow cytometric analysis. Three different culture media including; (1) Transforming growth factor beta 1 (TGF-β1)+ bone morphogenic protein 4, (2) TGF-β1+ l-ascorbic acid (l-AA) and (3) Horse serum, were compared for differentiation of CD146+ PCs to SMCs by IFS and real time polymerase chain reaction. As a result, in the case of SMC differentiation of CD146+ PCs, second culture medium including TGF-β1 and l-AA was found to be more effective than other two media. These results are important for establishing proper culture conditions for in vitro SMC differentiation of CD146+ PCs.  相似文献   
10.
Intertidal corals have been under-studied yet they provide scope for understanding adaptation and acclimatisation of corals to marginal conditions. Corals in intertidal rock pools along the east coast of South Africa withstand large temperature fluctuations, and marginal conditions for survival and growth. Four sites along the KwaZulu-Natal (KZN) coastline were sampled to determine latitudinal differences in coral communities, from 27°S to 31°S. Water temperature of rock pools at each site was monitored to see if temperature determined coral diversity in intertidal pools. Sixteen coral species were present in rock pools overall. Each of three sites in northern and central KZN hosted 12 coral taxa whereas only six taxa occurred at the most southern site. Anomastrea irregularis was the most abundant species at all sites, followed by Pocillopora verrucosa and P. damicornis. Unexpectedly, rock pool temperatures did not show a trend with latitude and thus cannot explain this decline in coral diversity. Temperatures in isolated rock pools showed large summer day time fluctuations of more than 10 °C at spring tide. However, temperatures drop substantially at high tide, lowering the mean rock pool temperature and possibly allowing these coral communities to persist in the marginal conditions of rock pools in South Africa.  相似文献   
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