BEDwARS: a robust Bayesian approach to bulk gene expression deconvolution with noisy reference signatures.

Differential gene expression in bulk transcriptomics data can reflect change of transcript abundance within a cell type and/or change in the proportions of cell types. Expression deconvolution methods can help differentiate these scenarios. BEDwARS is a Bayesian deconvolution method designed to address differences between reference signatures of cell types and corresponding true signatures underlying bulk transcriptomic profiles. BEDwARS is more robust to noisy reference signatures and outperforms leading in-class methods for estimating cell type proportions and signatures. Application of BEDwARS to dihydropyridine dehydrogenase deficiency identified the possible involvement of ciliopathy and impaired translational control in the etiology of the disorder.

Evaluating Statistical Multiple Sequence Alignment in Comparison to Other Alignment Methods on Protein Data Sets.

The estimation of multiple sequence alignments of protein sequences is a basic step in many bioinformatics pipelines, including protein structure prediction, protein family identification, and phylogeny estimation. Statistical coestimation of alignments and trees under stochastic models of sequence evolution has long been considered the most rigorous technique for estimating alignments and trees, but little is known about the accuracy of such methods on biological benchmarks. We report the results of an extensive study evaluating the most popular protein alignment methods as well as the statistical coestimation method BAli-Phy on 1192 protein data sets from established benchmarks as well as on 120 simulated data sets. Our study (which used more than 230 CPU years for the BAli-Phy analyses alone) shows that BAli-Phy has better precision and recall (with respect to the true alignments) than the other alignment methods on the simulated data sets but has consistently lower recall on the biological benchmarks (with respect to the reference alignments) than many of the other methods. In other words, we find that BAli-Phy systematically underaligns when operating on biological sequence data but shows no sign of this on simulated data. There are several potential causes for this change in performance, including model misspecification, errors in the reference alignments, and conflicts between structural alignment and evolutionary alignments, and future research is needed to determine the most likely explanation. We conclude with a discussion of the potential ramifications for each of these possibilities. [BAli-Phy; homology; multiple sequence alignment; protein sequences; structural alignment.].

The Effects of Oltipraz on Tissue Regeneration in the Process of Wound Healing: A Stereological Study.

OBJECTIVE: To determine the effects of topical administration of 20% oltipraz solution on histomorphometrical and stereological aspects of skin tissue in full thickness skin wounds in laboratory rats. METHODS: Thirty-six male Wistar portion rats (220±20 g) were randomly divided into three groups (n=12). On the first day of experimentation, a 1-cm2 circular wound was made on the posterior surface of neck in all rats by removing a full thickness skin piece immediately after induction of anesthesia with ether inhalation. One group was treated with vehicle solution (DMSO alone). The second group was treated daily with 20% oltipraz solution, and the third group, the control group, received no treatment. The wound closure rate was estimated our previously described method. The volume density of collagen bundles, vessels, and hair follicles, the vessels' length density, mean diameter of vessels and also fibroblast population were estimated by using stereological methods. RESULTS: The oltipraz group indicated a significantly higher improvement (6.26% of the wound surface per day) than control and the vehicle treated groups (p=0.032); furthermore, there was inconsiderable difference between the rate of wound closure in the group treated with vehicle (4.93% per day) and the control group (4.43% per day). CONCLUSION: Oltipraz  has  positive  influence on  fibroblast proliferation  and  re-pithelization.  A  noticeable observation in our study was absence of scar formation in wounds which were treated by oltipraz and can be mentioned as an advantage of this drug.