A clinically validated human capillary blood transcriptome test for global systems biology studies.

To prevent and treat chronic diseases, including cancer, a global application of systems biology is needed. We report here a whole blood transcriptome test that needs only 50 μl of capillary (fingerprick) blood. This test is suitable for global applications because the samples are preserved at ambient temperature for up to 4 weeks and the RNA preservative inactivates all pathogens, enabling safe transportation.

Correction to: Implications of sequence variation on the evolution of rRNA.

The article Implications of sequence variation on the evolution of rRNA, written by Matthew M. Parks, Chad M. Kurylo, Jake E.

Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease.

Ribosome biogenesis is a canonical hallmark of cell growth and proliferation. Here we show that execution of Epithelial-to-Mesenchymal Transition (EMT), a migratory cellular program associated with development and tumor metastasis, is fueled by upregulation of ribosome biogenesis during G1/S arrest. This unexpected EMT feature is independent of species and initiating signal, and is accompanied by release of the repressive nucleolar chromatin remodeling complex (NoRC) from rDNA, together with recruitment of the EMT-driving transcription factor Snai1 (Snail1), RNA Polymerase I (Pol I) and the Upstream Binding Factor (UBF).

Implications of sequence variation on the evolution of rRNA.

The evolution of the multi-copy family of ribosomal RNA (rRNA) genes is unique in regard to its genetics and genome evolution. Paradoxically, rRNA genes are highly homogenized within and between individuals, yet they are globally distinct between species. Here, we discuss the implications for models of rRNA gene evolution in light of our recent discoveries that ribosomes bearing rRNA sequence variants can affect gene expression and physiology and that intra-individual rRNA alleles exhibit both context- and tissue-specific expression.

ADAM10 controls the differentiation of the coronary arterial endothelium.

The coronary vasculature is crucial for normal heart function, yet much remains to be learned about its development, especially the maturation of coronary arterial endothelium. Here, we show that endothelial inactivation of ADAM10, a key regulator of Notch signaling, leads to defects in coronary arterial differentiation, as evidenced by dysregulated genes related to Notch signaling and arterial identity. Moreover, transcriptome analysis indicated reduced EGFR signaling in A10ΔEC coronary endothelium.

Endogenous rRNA Sequence Variation Can Regulate Stress Response Gene Expression and Phenotype.

Prevailing dogma holds that ribosomes are uniform in composition and function. Here, we show that nutrient limitation-induced stress in E. coli changes the relative expression of rDNA operons to alter the rRNA composition within the actively translating ribosome pool.

Using controls to limit false discovery in the era of big data.

Background: Procedures for controlling the false discovery rate (FDR) are widely applied as a solution to the multiple comparisons problem of high-dimensional statistics. Current FDR-controlling procedures require accurately calculated p-values and rely on extrapolation into the unknown and unobserved tails of the null distribution. Both of these intermediate steps are challenging and can compromise the reliability of the results.

Variant ribosomal RNA alleles are conserved and exhibit tissue-specific expression.

The ribosome, the integration point for protein synthesis in the cell, is conventionally considered a homogeneous molecular assembly that only passively contributes to gene expression. Yet, epigenetic features of the ribosomal DNA (rDNA) operon and changes in the ribosome's molecular composition have been associated with disease phenotypes, suggesting that the ribosome itself may possess inherent regulatory capacity. Analyzing whole-genome sequencing data from the 1000 Genomes Project and the Mouse Genomes Project, we find that rDNA copy number varies widely across individuals, and we identify pervasive intra- and interindividual nucleotide variation in the 5, 5.

An exact test for comparing a fixed quantitative property between gene sets.

Motivation: A significant difference in the distribution of a feature between two gene sets can provide insight into function or regulation. This statistical setting differs from much of hypothesis testing theory because the genome is often considered to be effectively fixed, finite and entirely known in commonly studied organisms, such as human. The Mann-Whitney U test is commonly employed in this scenario despite the assumptions of the test not being met, leading to unreliable and generally underpowered results.

Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I.

Ribosome biogenesis is essential for cell growth and proliferation and is commonly elevated in cancer. Accordingly, numerous oncogene and tumor suppressor signaling pathways target rRNA synthesis. In breast cancer, non-canonical Wnt signaling by Wnt5a has been reported to antagonize tumor growth.

Genome Sequence and Analysis of Escherichia coli MRE600, a Colicinogenic, Nonmotile Strain that Lacks RNase I and the Type I Methyltransferase, EcoKI.

Escherichia coli strain MRE600 was originally identified for its low RNase I activity and has therefore been widely adopted by the biomedical research community as a preferred source for the expression and purification of transfer RNAs and ribosomes. Despite its widespread use, surprisingly little information about its genome or genetic content exists. Here, we present the first de novo assembly and description of the MRE600 genome and epigenome.

Functional Dynamics within the Human Ribosome Regulate the Rate of Active Protein Synthesis.

The regulation of protein synthesis contributes to gene expression in both normal physiology and disease, yet kinetic investigations of the human translation mechanism are currently lacking. Using single-molecule fluorescence imaging methods, we have quantified the nature and timing of structural processes in human ribosomes during single-turnover and processive translation reactions. These measurements reveal that functional complexes exhibit dynamic behaviors and thermodynamic stabilities distinct from those observed for bacterial systems.

Detecting non-allelic homologous recombination from high-throughput sequencing data.

Non-allelic homologous recombination (NAHR) is a common mechanism for generating genome rearrangements and is implicated in numerous genetic disorders, but its detection in high-throughput sequencing data poses a serious challenge. We present a probabilistic model of NAHR and demonstrate its ability to find NAHR in low-coverage sequencing data from 44 individuals. We identify NAHR-mediated deletions or duplications in 109 of 324 potential NAHR loci in at least one of the individuals.