NeMu: a comprehensive pipeline for accurate reconstruction of neutral mutation spectra from evolutionary data.

The recognized importance of mutational spectra in molecular evolution is yet to be fully exploited beyond human cancer studies and model organisms. The wealth of intraspecific polymorphism data in the GenBank repository, covering a broad spectrum of genes and species, presents an untapped opportunity for detailed mutational spectrum analysis. Existing methods fall short by ignoring intermediate substitutions on the inner branches of phylogenetic trees and lacking the capability for cross-species mutational comparisons.

Nontriplet feature of genetic code in ciliates is a result of neutral evolution.

The triplet nature of the genetic code is considered a universal feature of known organisms. However, frequent stop codons at internal mRNA positions in ciliates ultimately specify ribosomal frameshifting by one or two nucleotides depending on the context, thus posing a nontriplet feature of the genetic code of these organisms. Here, we sequenced transcriptomes of eight species and assessed evolutionary patterns arising at frameshift sites.

Sense and antisense RNA products of the gene can affect motility and chemotaxis acting independent of the UxuR protein.

Small non-coding and antisense RNAs are widespread in all kingdoms of life, however, the diversity of their functions in bacteria is largely unknown. Here, we study RNAs synthesised from divergent promoters located in the 3'-end of the gene, encoding transcription factor regulating hexuronate metabolism in These overlapping promoters were predicted with rather high scores, effectively bound RNA polymerase and and were capable of initiating transcription in sense and antisense directions. The genome-wide correlation between promoter scores and RNA polymerase binding and was higher for promoters located on the antisense strands of the genes, however, sense promoters within the gene were more active.

A hierarchy in clusters of cephalopod mRNA editing sites.

RNA editing in the form of substituting adenine with inosine (A-to-I editing) is the most frequent type of RNA editing in many metazoan species. In most species, A-to-I editing sites tend to form clusters and editing at clustered sites depends on editing of the adjacent sites. Although functionally important in some specific cases, A-to-I editing usually is rare.

Adaptive evolution at mRNA editing sites in soft-bodied cephalopods.

Background: The bulk of variability in mRNA sequence arises due to mutation-change in DNA sequence which is heritable if it occurs in the germline. However, variation in mRNA can also be achieved by post-transcriptional modification including mRNA editing, changes in mRNA nucleotide sequence that mimic the effect of mutations. Such modifications are not inherited directly; however, as the processes affecting them are encoded in the genome, they have a heritable component, and therefore can be shaped by selection.

Influence of the spacer region between the Shine-Dalgarno box and the start codon for fine-tuning of the translation efficiency in Escherichia coli.

Translation efficiency contributes several orders of magnitude difference in the overall yield of exogenous gene expression in bacteria. In diverse bacteria, the translation initiation site, whose sequence is the primary determinant of the translation performance, is comprised of the start codon and the Shine-Dalgarno box located upstream. Here, we have examined how the sequence of a spacer between these main components of the translation initiation site contributes to the yield of synthesized protein.

Identification of Transcriptional Regulators of Psoriasis from RNA-Seq Experiments.

Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the molecular mechanisms of regulation of the disease we performed RNA sequencing (RNA-Seq) analysis of 14 pairs of skin samples collected from psoriatic patients. Subsequent pathway analysis and an extraction of transcriptional regulators governing psoriasis-associated pathways was executed using a combination of MetaCore Interactome enrichment tool and cisExpress algorithm, and followed by comparison to a set of previously described psoriasis response elements.

Analysis of cis-Regulatory Elements in Gene Co-expression Networks in Cancer.

Analysis of gene co-expression networks is a powerful "data-driven" tool, invaluable for understanding cancer biology and mechanisms of tumor development. Yet, despite of completion of thousands of studies on cancer gene expression, there were few attempts to normalize and integrate co-expression data from scattered sources in a concise "meta-analysis" framework. Here we describe an integrated approach to cancer expression meta-analysis, which combines generation of "data-driven" co-expression networks with detailed statistical detection of promoter sequence motifs within the co-expression clusters.

The Genetic Architecture of Major Depressive Disorder in Han Chinese Women.

Importance: Despite the moderate, well-demonstrated heritability of major depressive disorder (MDD), there has been limited success in identifying replicable genetic risk loci, suggesting a complex genetic architecture. Research is needed to quantify the relative contribution of classes of genetic variation across the genome to inform future genetic studies of MDD.

Objectives: To apply aggregate genetic risk methods to clarify the genetic architecture of MDD by estimating and partitioning heritability by chromosome, minor allele frequency, and functional annotations and to test for enrichment of rare deleterious variants.

Hidden Markov models for evolution and comparative genomics analysis.

The problem of reconstruction of ancestral states given a phylogeny and data from extant species arises in a wide range of biological studies. The continuous-time Markov model for the discrete states evolution is generally used for the reconstruction of ancestral states. We modify this model to account for a case when the states of the extant species are uncertain.