D-ORB: A Web Server to Extract Structural Features of Related But Unaligned RNA Sequences.

Identifying the common structural elements of functionally related RNA sequences (family) is usually based on an alignment of the sequences, which is often subject to human bias and may not be accurate. The resulting covariance model (CM) provides probabilities for each base to covary with another, which allows to support evolutionarily the formation of double helical regions and possibly pseudoknots. The coexistence of alternative folds in RNA, resulting from its dynamic nature, may lead to the potential omission of motifs by CM. To overcome this limitation, we present D-ORB, a system of algorithms that identifies overrepresented motifs in the secondary conformational landscapes of a family when compared to those of unrelated sequences. The algorithms are bundled into an easy-to-use website allowing users to submit a family, and optionally provide unrelated sequences. D-ORB produces a non-pseudoknotted secondary structure based on the overrepresented motifs, a deep neural network classifier and two decision trees. When used to model an Rfam family, D-ORB fits overrepresented motifs in the corresponding Rfam structure; more than a hundred Rfam families have been modeled. The statistical approach behind D-ORB derives the structural composition of an RNA family, making it a valuable tool for analyzing and modeling it. Its easy-to-use interface and advanced algorithms make it an essential resource for researchers studying RNA structure. D-ORB is available at https://d-orb.major.iric.ca/.

Large differences in blood measures, tissue weights, and focal areas of damage 1 year after postseizure treatment with acepromazine or ketamine.

Approximately 1 year after rats were seized as young adults with lithium (3 mEq/kg) and pilocarpine (30 mg/kg) and given acepromazine or ketamine, 18 blood measures, wet tissue weights, and detailed damage scores for 107 brain structures were completed. Compared with normal and ketamine-treated rats, acepromazine-treated seized rats (total n=54) had lighter pancreata and spleens and elevated aspartate aminotransferase and alanine aminotransferase blood levels. Even though average damage did not differ, the mosaic of brain damage completely discriminated the two seized groups. Differential effects of postseizure treatment on functions of the thyroid, pancreas, and spleen were indicated. Ketamine-treated seized rats were healthier than acepromazine-treated seized rats or normal rats. This experiment demonstrates the importance of whole-organism assessment and that the single administration of a specific drug after onset of status epilepticus can produce marked differences in the evolution of brain damage and its influence on specific organs for the rest of the animal's life.

Simultaneous inference of haplotypes and alleles at a causal gene.

We present a methodology which jointly infers haplotypes and the causal alleles at a gene influencing a given trait. Often in human genetic studies, the available data consists of genotypes (series of genetic markers along the chromosomes) and a phenotype. However, for many genetic analyses, one needs haplotypes instead of genotypes. Our methodology is not only able to estimate haplotypes conditionally on the disease status, but is also able to infer the alleles at the unknown disease locus. Some applications of our methodology are in genetic mapping and in genetic counseling.