Computational efforts to identify functional elements within genomes leverage comparative sequence information by looking for regions that exhibit evidence of selective constraint. One way of ...detecting constrained elements is to follow a bottom-up approach by computing constraint scores for individual positions of a multiple alignment and then defining constrained elements as segments of contiguous, highly scoring nucleotide positions. Here we present GERP++, a new tool that uses maximum likelihood evolutionary rate estimation for position-specific scoring and, in contrast to previous bottom-up methods, a novel dynamic programming approach to subsequently define constrained elements. GERP++ evaluates a richer set of candidate element breakpoints and ranks them based on statistical significance, eliminating the need for biased heuristic extension techniques. Using GERP++ we identify over 1.3 million constrained elements spanning over 7% of the human genome. We predict a higher fraction than earlier estimates largely due to the annotation of longer constrained elements, which improves one to one correspondence between predicted elements with known functional sequences. GERP++ is an efficient and effective tool to provide both nucleotide- and element-level constraint scores within deep multiple sequence alignments.
Many DNA variants have been identified on more than 300 diseases and traits using Genome-Wide Association Studies (GWASs). Some have been validated using deep sequencing, but many fewer have been ...validated functionally, primarily focused on non-synonymous coding SNPs (nsSNPs). It is an open question whether synonymous coding SNPs (sSNPs) and other non-coding SNPs can lead to as high odds ratios as nsSNPs. We conducted a broad survey across 21,429 disease-SNP associations curated from 2,113 publications studying human genetic association, and found that nsSNPs and sSNPs shared similar likelihood and effect size for disease association. The enrichment of disease-associated SNPs around the 80(th) base in the first introns might provide an effective way to prioritize intronic SNPs for functional studies. We further found that the likelihood of disease association was positively associated with the effect size across different types of SNPs, and SNPs in the 3' untranslated regions, such as the microRNA binding sites, might be under-investigated. Our results suggest that sSNPs are just as likely to be involved in disease mechanisms, so we recommend that sSNPs discovered from GWAS should also be examined with functional studies.
Computational efforts to identify functional elements within genomes leverage comparative sequence information by looking for regions that exhibit evidence of selective constraint. One way of ...detecting constrained elements is to follow a bottom-up approach by computing constraint scores for individual positions of a multiple alignment and then defining constrained elements as segments of contiguous, highly scoring nucleotide positions. Here we present GERP++, a new tool that uses maximum likelihood evolutionary rate estimation for position-specific scoring and, in contrast to previous bottom-up methods, a novel dynamic programming approach to subsequently define constrained elements. GERP++ evaluates a richer set of candidate element breakpoints and ranks them based on statistical significance, eliminating the need for biased heuristic extension techniques. Using GERP++ we identify over 1.3 million constrained elements spanning over 7% of the human genome. We predict a higher fraction than earlier estimates largely due to the annotation of longer constrained elements, which improves one to one correspondence between predicted elements with known functional sequences. GERP++ is an efficient and effective tool to provide both nucleotide- and element-level constraint scores within deep multiple sequence alignments.
Here we describe Cryptogamic Russian Information System (CRIS), a web service cataloguing the biodiversity of cryptogams: cyanobacteria, fungi (including lichens), and bryophytes. CRIS incorporates a ...wide spectrum of data types, allowing for greater ease of use. It is possible to print the labels for herbarium collections, to input literature references, media files, etc., using CRIS which has a flexible interface and specific technical abilities. Currently, CRIS contains ~ 90,000 herbarium records, including 67,861 records of bryophytes, 12,486 records of lichens and 3,800 records of cyanobacteria. Data analysis of the different taxonomic groups is provided below. Perspectives and directions for the future development of CRIS are discussed.
In this work, we study some aspects of self-structuring of Li
2O–B
2O
3 and Li
2O–B
2O
3–MoO
3 molten media depending of the composition, temperature, starting materials, etc. and comment them within ...the frames our model concepts. The main results were obtained by the methods of spectroscopy of glasses, whereas complementary results, by in situ diffractometry and spectroscopy of melts and quantum-chemical calculations. These results are compared with our practice on growing LiB
3O
5 single crystals and some recommendations are given concerning the procedure. It is shown that the application of a rather simple spectroscopic testing for the sample of borate molten media can be useful for improving the technology of growth of large single crystals for practical use.
Molten sodium salts were studied using in situ diffractiometry and Raman spectroscopy with the aim to establish the composition, arrangement, and tendencies in the temperature evolution of major ...structural units (SU). The obtained results agree well with the quantum-chemical calculations of the models of corresponding cation–anion associative complexes (AC). A conclusion is made that supports the interpretation of AC with a temperature-dependent association–dissociation constant as a high reactivity SU of polycomponent melts, in contrast with the passive ones, i.e., high-polycondensed fragments of anion groupings. The AC with the configuration predominant in precursor clusters as well as the structure-forming cations can be regarded as elementary crystal growth units. The NMR-spectroscopy of cesium–borate glasses suggests varying structural state and different effects of the structure-forming cations in the polycomponent systems.
We evaluate using of metal mirrors over-coated with transparent protection layer for the in-vessel diagnostic systems in reactor-grade fusion devices. Ideally, these should satisfy the contradictory ...demands of high reflectivity and small rate degradation when being bombarded by CX atoms. The serious threat to the performance of diagnostic mirrors is surface contamination with carbon-based material eroded from carbon tiles. Via coupling the protective layer to a bulk mirror we can mitigate the deposit infiuence on the reflectance spectra. The regards are given to survivability in plasma environment of protected coated metallic mirrors.
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