BackgroundDespite their vast biological implication, the relevance of short tandem repeats (STRs)/microsatellites to the protein-coding gene translation initiation sites (TISs) remains largely unknown.MethodsWe performed an Ensembl-based comparative genomics study of all annotated orthologous TIS-flanking sequences in human and 46 other species across vertebrates, on the genomic DNA and cDNA platforms (755,956 TISs), aimed at identifying human-specific STRs in this interval. The collected data were used to examine the hypothesis of a link between STRs and TISs. BLAST was used to compare the initial five amino acids (excluding the initial methionine), codons of which were flanked by STRs in human, with the initial five amino acids of all annotated proteins for the orthologous genes in other vertebrates (total of 5,314,979 pair-wise TIS comparisons on the genomic DNA and cDNA platforms) in order to compare the number of events in which human-specific and non-specific STRs occurred with homologous and non-homologous TISs (i.e., ≥ 50% and < 50% similarity of the five amino acids).ResultsWe detected differential distribution of the human-specific STRs in comparison to the overall distribution of STRs on the genomic DNA and cDNA platforms (Mann Whitney U test p = 1.4 × 10−11 and p < 7.9 × 10−11, respectively). We also found excess occurrence of non-homologous TISs with human-specific STRs and excess occurrence of homologous TISs with non-specific STRs on both platforms (p < 0.00001).ConclusionWe propose a link between STRs and TIS selection, based on the differential co-occurrence rate of human-specific STRs with non-homologous TISs and non-specific STRs with homologous TISs.Electronic supplementary materialThe online version of this article (10.1186/s40246-018-0181-3) contains supplementary material, which is available to authorized users.

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Background:Common carotid artery (CCA) ultrasound with measurement of intima-media thickness (IMT) is a safe and noninvasive technique for assessing subclinical atherosclerosis and determining cardiovascular risks. Moreover, the pattern of wall thickening in the brachial artery (BA) is rather diffuse compared to the carotid artery and may be a more sensitive indicator of long-term systemic exposure to risk factors. Therefore noninvasive evaluation of mechanical parameters changes of both arteries has gained the attention of researchers.Objectives:The aim of this study was to compare different edge detection techniques with speckle reducing anisotropic diffusion (SRAD) de-noising filter in ultrasound images of both arteries.Patients and Methods:In a cross-sectional design, an examination was performed on ten men with mean age of 40 ± 5 years from September 2012 to March 2013 through random sampling. An ultrasonic examination of the left CCA and BA was performed. The program was designed in the MATLAB software to extract consecutive images in JPEG format from the AVI. Another program was designed in the MATLAB software to apply regions of interest (ROI) on the IMT of the posterior wall of common carotid and brachial arteries. Next, different edge detections and SRAD filter were applied to the ROI, separately. Finally, the program measured mean-squared error (MSE) and peak signal to noise ratio (PSNR).Results:The lowest values of MSE and highest values of PSNR were achieved by Canny edge detection with de-noising SRAD filter for IMT of left CCA and BA in 90 frames.Conclusions:Based on the result, by measuring the MSE and PSNR, this study showed Canny edge detection with SRAD filter is better than other edge detections in terms of speckle suppression and details preservation in CCA and BA ultrasound images.

The present study assessed the use of filters for noise reduction in ultrasound images of the common carotid artery (CCA) and brachial artery using intima–media thickness, which is a safe and non‐invasive technique for determining subclinical atherosclerosis and cardiovascular risk. A new combined speckle reducing anisotropic diffusion (SRAD) filter for noise reduction is then proposed. Ultrasonic examination of both arteries was performed on 30 men (aged 40 ± 5 years). The programme was designed using MATLAB software to extract consecutive images in bit map format from the audio video interleaves. An additional programme was designed in MATLAB to apply the region of interest (ROI) to the thickness of the intima–media of the posterior walls of the arteries. Block‐matching techniques were used to estimate arterial motion from ultrasound images of the B‐mode CCA and brachial artery. Different noise reduction filters and Canny edge detection were carried out separately in the ROI. The programme measured mean square error (MSE) and peak signal‐to‐noise ratio (PSNR). The results demonstrated that the new combined SRAD filter with Canny edge detection identified the lowest value for MSE and the highest value for PSNR in 90 consecutive frames (∼3 cardiac cycles). The results indicate that MSE and PSNR were better detected by the proposed combined SRAD filter with Canny edge detection than did several commonly used filters with Canny detection for speckle suppression and preservation detail in carotid and brachial arteries ultrasound images.

BackgroundMachine learning can effectively nominate novel genes for various research purposes in the laboratory. On a genome-wide scale, we implemented multiple databases and algorithms to predict and prioritize the human aging genes (PPHAGE).ResultsWe fused data from 11 databases, and used Naïve Bayes classifier and positive unlabeled learning (PUL) methods, NB, Spy, and Rocchio-SVM, to rank human genes in respect with their implication in aging. The PUL methods enabled us to identify a list of negative (non-aging) genes to use alongside the seed (known age-related) genes in the ranking process. Comparison of the PUL algorithms revealed that none of the methods for identifying a negative sample were advantageous over other methods, and their simultaneous use in a form of fusion was critical for obtaining optimal results (PPHAGE is publicly available at https://cbb.ut.ac.ir/pphage).ConclusionWe predict and prioritize over 3,000 candidate age-related genes in human, based on significant ranking scores. The identified candidate genes are associated with pathways, ontologies, and diseases that are linked to aging, such as cancer and diabetes. Our data offer a platform for future experimental research on the genetic and biological aspects of aging. Additionally, we demonstrate that fusion of PUL methods and data sources can be successfully used for aging and disease candidate gene prioritization.

The development of a safe and effective vaccine is essential to protect populations against coronavirus disease 2019 (COVID‐19). There are several vaccine candidates under investigation with different mechanisms of action. In the present study, we have evaluated the safety and immunogenicity of a recombinant receptor‐binding domain (RBD)‐based protein subunit vaccine (Noora vaccine) against COVID‐19 in adults. This Phase 1 trial is a randomized, double‐blind, placebo‐controlled study to evaluate the safety and immunogenicity of the recombinant RBD‐based protein subunit vaccine (Noora vaccine) against COVID‐19 in healthy adults volunteers. Eligible participants were included in this study after evaluating their health status and considering the exclusion criteria. They were then randomized into three groups and received three doses of vaccine (80 µg, 120 µg, and placebo) on Days 0, 21, and 35. Primary outcomes including solicited, unsolicited, and medically attended adverse events were recorded during this study. Secondary outcomes including the humoral and cellular immunity (including anti‐RBD IgG antibody and neutralizing antibody) were measured on Days 0, 21, 28, 35, 42, and 49 by using the ELISA kit and the Virus Neutralization Test (VNT) was performed on day 49. Totally 70 cases were included in this Phase 1 trial and 60 of them completed the study. Safety assessments showed no severe adverse events. Local pain at the vaccine injection site occurred in 80% of the vaccinated volunteers. Induration and redness at the injection site were the other adverse reactions of this vaccine. There was no significant difference between the studied groups regarding adverse reactions. Anti‐RBD IgG antibody and neutralizing antibody assessment showed significant seroconversion in comparison to the placebo group (80%, and 100% respectively, p < 0.001). The cellular immunity panel also showed mild to moderate induction of TH1 responses and the VNT showed 78% of seroprotection. The results of this Phase 1 trial showed acceptable safety without serious adverse events and significant seroconversions in the humoral and cellular immunity panel. The dose of 80 µg is an appropriate dose for injection in the next phases of the trial.

Background While of predominant abundance across vertebrate genomes and significant biological implications, the relevance of short tandem repeats (STRs) (also known as microsatellites) to speciation remains largely elusive and attributed to random coincidence for the most part. Here we collected data on the whole-genome abundance of mono-, di-, and trinucleotide STRs in nine species, encompassing rodents and primates, including rat, mouse, olive baboon, gelada, macaque, gorilla, chimpanzee, bonobo, and human. The collected data were used to analyze hierarchical clustering of the STR abundances in the selected species. Results We found massive differential STR abundances between the rodent and primate orders. In addition, while numerous STRs had random abundance across the nine selected species, the global abundance conformed to three consistent < clusters>, as follows: <rat, mouse>, <gelada, macaque, olive baboon>, and <gorilla, chimpanzee, bonobo, human>, which coincided with the phylogenetic distances of the selected species (p < 4E-05). Exceptionally, in the trinucleotide STR compartment, human was significantly distant from all other species. Conclusion Based on hierarchical clustering, we propose that the global abundance of STRs is non-random in rodents and primates, and probably had a determining impact on the speciation of the two orders. We also propose the STRs and STR lengths, which predominantly conformed to the phylogeny of the selected species, exemplified by (t)10, (ct)6, and (taa4). Phylogenetic and experimental platforms are warranted to further examine the observed patterns and the biological mechanisms associated with those STRs.

Background While the evolutionary divergence of cis-regulatory sequences impacts translation initiation sites (TISs), the implication of tandem repeats (TRs) in TIS selection remains largely elusive. Here, we employed the TIS homology concept to study a possible link between TRs of all core lengths and repeats with TISs. Methods Human, as reference sequence, and 83 other species were selected, and data was extracted on the entire protein-coding genes (n = 1,611,368) and transcripts (n = 2,730,515) annotated for those species from Ensembl 102. Following TIS identification, two different weighing vectors were employed to assign TIS homology, and the co-occurrence pattern of TISs with the upstream flanking TRs was studied in the selected species. The results were assessed in 10-fold cross-validation. Results On average, every TIS was flanked by 1.19 TRs of various categories within its 120 bp upstream sequence, per species. We detected statistically significant enrichment of non-homologous human TISs co-occurring with human-specific TRs. On the contrary, homologous human TISs co-occurred significantly with non-human-specific TRs. 2991 human genes had at least one transcript, TIS of which was flanked by a human-specific TR. Text mining of a number of the identified genes, such as CACNA1A, EIF5AL1, FOXK1, GABRB2, MYH2, SLC6A8, and TTN, yielded predominant expression and functions in the human brain and/or skeletal muscle. Conclusion We conclude that TRs ubiquitously flank and contribute to TIS selection at the trans-species level. Future functional analyses, such as a combination of genome editing strategies and in vitro protein synthesis may be employed to further investigate the impact of TRs on TIS selection.