Structural Peculiarities of Human Genes Which Expression Increases in Response to Stress
We studied structural peculiarities of 123 human genes which were previously identified as genes of early response to exercise stress. Compared to protein-coding genes in general, their structure revealed some peculiarities: they are shorter in both coding and non-coding regions and contain fewer introns. This result is in good agreement with the similar results reported for stress-responding genes in other species (yeasts, thale cress, and mice).
A typical eukaryotic gene is comprised of alternating stretches of regions, exons and introns, retained in and spliced out a mature mRNA, respectively. Although the length of introns may vary substantially among organisms, a large fraction of genes contains short introns in many species. Notably, some Ciliates (Paramecium and Nyctotherus) possess only ultra-short introns, around 25 bp long. In Paramecium, ultra-short introns with length divisible by three (3n) are under strong evolutionary pressure and have a high frequency of in-frame stop codons, which, in the case of intron retention, cause premature termination of mRNA translation and consequent degradation of the mis-spliced mRNA by the nonsense-mediated decay mechanism. Here, we analyzed introns in five genera of Ciliates, Paramecium, Tetrahymena, Ichthyophthirius, Oxytricha, and Stylonychia. Introns can be classified into two length classes in Tetrahymena and Ichthyophthirius (with means 48 bp, 69 bp, and 55 bp, 64 bp, respectively), but, surprisingly, comprise three distinct length classes in Oxytricha and Stylonychia (with means 33-35 bp, 47-51 bp, and 78-80 bp). In most ranges of the intron lengths, 3n introns are underrepresented and have a high frequency of in-frame stop codons in all studied species. Introns of Paramecium, Tetrahymena, and Ichthyophthirius are preferentially located at the 5' and 3' ends of genes, whereas introns of Oxytricha and Stylonychia are strongly skewed towards the 5' end. Analysis of evolutionary conservation shows that, in each studied genome, a significant fraction of intron positions is conserved between the orthologs, but intron lengths are not correlated between the species. In summary, our study provides a detailed characterization of introns in several genera of Ciliates and highlights some of their distinctive properties, which, together, indicate that splicing spellchecking is a universal and evolutionarily conserved process in the biogenesis of short introns in various representatives of Ciliates.
IRBIS is a computational pipeline for detecting conserved complementary regions in unaligned orthologous sequences. Unlike other methods, it follows the "first-fold-then-align" principle in which all possible combinations of complementary k-mers are searched for simultaneous conservation. The novel trimming procedure reduces the size of the search space and improves the performance to the point where large-scale analyses of intra- and intermolecular RNA-RNA interactions become possible. In this article, I provide a rigorous description of the method, benchmarking on simulated and real data, and a set of stringent predictions of intramolecular RNA structure in placental mammals, drosophilids, and nematodes. I discuss two particular cases of long-range RNA structures that are likely to have a causal effect on single- and multiple-exon skipping, one in the mammalian gene Dystonin and the other in the insect gene Ca-α1D. In Dystonin, one of the two complementary boxes contains a binding site of Rbfox protein similar to one recently described in Enah gene. I also report that snoRNAs and long noncoding RNAs (lncRNAs) have a high capacity of base-pairing to introns of protein-coding genes, suggesting possible involvement of these transcripts in splicing regulation. I also find that conserved sequences that occur equally likely on both strands of DNA (e.g., transcription factor binding sites) contribute strongly to the false-discovery rate and, therefore, would confound every such analysis. IRBIS is an open-source software that is available at http://genome.crg.es/~dmitri/irbis/.
Eukaryotic protein-coding genes consist of exons and introns. Exon–intron borders are conserved between species and thus their changes might be observed only on quite long evolutionary distances. One of the rarest types of change, in which intron relocates over a short distance, is called "intron sliding", but the reality of this event has been debated for a long time. The main idea of a search for intron sliding is to use the most accurate genome annotation and genome sequence, as well as high-quality transcriptome data. We applied them in a search for sliding introns in mammals in order to widen knowledge about the presence or absence of such phenomena in this group.
We didn’t find any significant evidence of intron sliding in the primate group (human, chimpanzee, rhesus macaque, crab-eating macaque, green monkey, marmoset). Only one possible intron sliding event supported by a set of high quality transcriptomes was observed between EIF1AX human and sheep gene orthologs. Also, we checked a list of previously observed intron sliding events in mammals and showed that most likely they are artifacts of genome annotations and are not shown in subsequent annotation versions as well as are not supported by transcriptomic data.
We assume that intron sliding is indeed a very rare evolutionary event if it exists at all. Every case of intron sliding needs a lot of supportive data for detection and confirmation.
A model for organizing cargo transportation between two node stations connected by a railway line which contains a certain number of intermediate stations is considered. The movement of cargo is in one direction. Such a situation may occur, for example, if one of the node stations is located in a region which produce raw material for manufacturing industry located in another region, and there is another node station. The organization of freight traﬃc is performed by means of a number of technologies. These technologies determine the rules for taking on cargo at the initial node station, the rules of interaction between neighboring stations, as well as the rule of distribution of cargo to the ﬁnal node stations. The process of cargo transportation is followed by the set rule of control. For such a model, one must determine possible modes of cargo transportation and describe their properties. This model is described by a ﬁnite-dimensional system of diﬀerential equations with nonlocal linear restrictions. The class of the solution satisfying nonlocal linear restrictions is extremely narrow. It results in the need for the “correct” extension of solutions of a system of diﬀerential equations to a class of quasi-solutions having the distinctive feature of gaps in a countable number of points. It was possible numerically using the Runge–Kutta method of the fourth order to build these quasi-solutions and determine their rate of growth. Let us note that in the technical plan the main complexity consisted in obtaining quasi-solutions satisfying the nonlocal linear restrictions. Furthermore, we investigated the dependence of quasi-solutions and, in particular, sizes of gaps (jumps) of solutions on a number of parameters of the model characterizing a rule of control, technologies for transportation of cargo and intensity of giving of cargo on a node station.
Event logs collected by modern information and technical systems usually contain enough data for automated process models discovery. A variety of algorithms was developed for process models discovery, conformance checking, log to model alignment, comparison of process models, etc., nevertheless a quick analysis of ad-hoc selected parts of a journal still have not get a full-fledged implementation. This paper describes an ROLAP-based method of multidimensional event logs storage for process mining. The result of the analysis of the journal is visualized as directed graph representing the union of all possible event sequences, ranked by their occurrence probability. Our implementation allows the analyst to discover process models for sublogs defined by ad-hoc selection of criteria and value of occurrence probability
Existing approaches suggest that IT strategy should be a reflection of business strategy. However, actually organisations do not often follow business strategy even if it is formally declared. In these conditions, IT strategy can be viewed not as a plan, but as an organisational shared view on the role of information systems. This approach generally reflects only a top-down perspective of IT strategy. So, it can be supplemented by a strategic behaviour pattern (i.e., more or less standard response to a changes that is formed as result of previous experience) to implement bottom-up approach. Two components that can help to establish effective reaction regarding new initiatives in IT are proposed here: model of IT-related decision making, and efficiency measurement metric to estimate maturity of business processes and appropriate IT. Usage of proposed tools is demonstrated in practical cases.