Detection of Atherosclerosis by Small RNA-Sequencing Analysis of Extracellular Vesicle Enriched Serum Samples.

Atherosclerosis can occur throughout the arterial vascular system and lead to various diseases. Early diagnosis of atherosclerotic processes and of individual disease patterns would be more likely to be successful if targeted therapies were available. For this, it is important to find reliable biomarkers that are easily accessible and with little inconvenience for patients.

Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas.

B cells have the unique property to somatically alter their immunoglobulin (IG) genes by V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR). Aberrant targeting of these mechanisms is implicated in lymphomagenesis, but the mutational processes are poorly understood. By performing whole genome and transcriptome sequencing of 181 germinal center derived B-cell lymphomas (gcBCL) we identified distinct mutational signatures linked to SHM and CSR.

uap: reproducible and robust HTS data analysis.

Background: A lack of reproducibility has been repeatedly criticized in computational research. High throughput sequencing (HTS) data analysis is a complex multi-step process. For most of the steps a range of bioinformatic tools is available and for most tools manifold parameters need to be set.

Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies.

Background: Anti-CD3 immunotherapy was initially approved for clinical use for renal transplantation rejection prevention. Subsequently, new generations of anti-CD3 antibodies have entered clinical trials for a broader spectrum of therapeutic applications, including cancer and autoimmune diseases. Despite their extensive use, little is known about the exact mechanism of these molecules, except that they are able to activate T cells, inducing an overall immunoregulatory and tolerogenic behavior.

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma.

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation.

Divergent evolution in the genomes of closely related lacertids, Lacerta viridis and L. bilineata, and implications for speciation.

Background: Lacerta viridis and Lacerta bilineata are sister species of European green lizards (eastern and western clades, respectively) that, until recently, were grouped together as the L. viridis complex. Genetic incompatibilities were observed between lacertid populations through crossing experiments, which led to the delineation of two separate species within the L.

RNA-seq analysis identifies different transcriptomic types and developmental trajectories of primary melanomas.

Recent studies revealed trajectories of mutational events in early melanomagenesis, but the accompanying changes in gene expression are far less understood. Therefore, we performed a comprehensive RNA-seq analysis of laser-microdissected melanocytic nevi (n = 23) and primary melanoma samples (n = 57) and characterized the molecular mechanisms of early melanoma development. Using self-organizing maps, unsupervised clustering, and analysis of pseudotime (PT) dynamics to identify evolutionary trajectories, we describe here two transcriptomic types of melanocytic nevi (N1 and N2) and primary melanomas (M1 and M2).

Rare Splice Variants in Long Non-Coding RNAs.

Long non-coding RNAs (lncRNAs) form a substantial component of the transcriptome and are involved in a wide variety of regulatory mechanisms. Compared to protein-coding genes, they are often expressed at low levels and are restricted to a narrow range of cell types or developmental stages. As a consequence, the diversity of their isoforms is still far from being recorded and catalogued in its entirety, and the debate is ongoing about what fraction of non-coding RNAs truly conveys biological function rather than being "junk".

DIEGO: detection of differential alternative splicing using Aitchison's geometry.

Motivation: Alternative splicing is a biological process of fundamental importance in most eukaryotes. It plays a pivotal role in cell differentiation and gene regulation and has been associated with a number of different diseases. The widespread availability of RNA-Sequencing capacities allows an ever closer investigation of differentially expressed isoforms.

Changes of bivalent chromatin coincide with increased expression of developmental genes in cancer.

Bivalent (poised or paused) chromatin comprises activating and repressing histone modifications at the same location. This combination of epigenetic marks at promoter or enhancer regions keeps genes expressed at low levels but poised for rapid activation. Typically, DNA at bivalent promoters is only lowly methylated in normal cells, but frequently shows elevated methylation levels in cancer samples.

Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells.

The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms.

DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control.

Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells.

A multi-split mapping algorithm for circular RNA, splicing, trans-splicing and fusion detection.

Numerous high-throughput sequencing studies have focused on detecting conventionally spliced mRNAs in RNA-seq data. However, non-standard RNAs arising through gene fusion, circularization or trans-splicing are often neglected. We introduce a novel, unbiased algorithm to detect splice junctions from single-end cDNA sequences.

Atypical RNAs in the coelacanth transcriptome.

Circular and apparently trans-spliced RNAs have recently been reported as abundant types of transcripts in mammalian transcriptome data. Both types of non-colinear RNAs are also abundant in RNA-seq of different tissue from both the African and the Indonesian coelacanth. We observe more than 8,000 lincRNAs with normal gene structure and several thousands of circularized and trans-spliced products, showing that such atypical RNAs form a substantial contribution to the transcriptome.

Mapping the RNA-Seq trash bin: unusual transcripts in prokaryotic transcriptome sequencing data.

Prokaryotic transcripts constitute almost always uninterrupted intervals when mapped back to the genome. Split reads, i.e.

Bayesian sampling of evolutionarily conserved RNA secondary structures with pseudoknots.

Motivation: Today many non-coding RNAs are known to play an active role in various important biological processes. Since RNA's functionality is correlated with specific structural motifs that are often conserved in phylogenetically related molecules, computational prediction of RNA structure should ideally be based on a set of homologous primary structures. But many available RNA secondary structure prediction programs that use sequence alignments do not consider pseudoknots or their estimations consist on a single structure without information on uncertainty.

PROSO II--a new method for protein solubility prediction.

Many fields of science and industry depend on efficient production of active protein using heterologous expression in Escherichia coli. The solubility of proteins upon expression is dependent on their amino acid sequence. Prediction of solubility from sequence is therefore highly valuable.