compPknots: A Framework for Parallel Prediction and Comparison of RNA Secondary Structures with Pseudoknots

Codes for RNA structure prediction based on energy minimization are usually very time and resource intensive. For this reason several codes have been significantly simplified: in some cases they are unable to predict complex secondary structures such as pseudoknots, while at other times they are able to predict structures with reduced lengths, or they are only able to predict some elementary and simple pseudoknots. Each of the existing codes has its strengths and weaknesses. Providing scientists with tools that are able to combine the strengths of the several codes is a worthwhile objective. To address this need, we present compPknots, a parallel framework that uses a combination of existing codes such as Pknots-RE and Pknots-RG, to predict RNA secondary structures concurrently and automatically compare them with reference structures from databases or literature. In this paper compPknots is used to compare and contrast the prediction accuracies of 217 RNA secondary structures from the PseudoBase database using Pknots-RE and Pknots-RG separately, or both together. Its parallel master-slave architecture allowed us to prove that combinations of prediction codes can provide scientists with higher prediction accuracies in a very short time

De Novo variants in EEF2 cause a neurodevelopmental disorder with benign external hydrocephalus

Item does not contain fulltextEukaryotic translation elongation factor 2 (eEF2) is a key regulatory factor in gene expression that catalyzes the elongation stage of translation. A functionally impaired eEF2, due to a heterozygous missense variant in the EEF2 gene, was previously reported in one family with spinocerebellar ataxia-26 (SCA26), an autosomal dominant adult-onset pure cerebellar ataxia. Clinical exome sequencing identified de novo EEF2 variants in three unrelated children presenting with a neurodevelopmental disorder (NDD). Individuals shared a mild phenotype comprising motor delay and relative macrocephaly associated with ventriculomegaly. Populational data and bioinformatic analysis underscored the pathogenicity of all de novo missense variants. The eEF2 yeast model strains demonstrated that patient-derived variants affect cellular growth, sensitivity to translation inhibitors and translational fidelity. Consequently, we propose that pathogenic variants in the EEF2 gene, so far exclusively associated with late-onset SCA26, can cause a broader spectrum of neurologic disorders, including childhood-onset NDDs and benign external hydrocephalus

Ribosomal protein gene RPL9 variants can differentially impair ribosome function and cellular metabolism

Contains fulltext : 218593.pdf (publisher's version ) (Open Access)Variants in ribosomal protein (RP) genes drive Diamond-Blackfan anemia (DBA), a bone marrow failure syndrome that can also predispose individuals to cancer. Inherited and sporadic RP gene variants are also linked to a variety of phenotypes, including malignancy, in individuals with no anemia. Here we report an individual diagnosed with DBA carrying a variant in the 5'UTR of RPL9 (uL6). Additionally, we report two individuals from a family with multiple cancer incidences carrying a RPL9 missense variant. Analysis of cells from these individuals reveals that despite the variants both driving pre-rRNA processing defects and 80S monosome reduction, the downstream effects are remarkably different. Cells carrying the 5'UTR variant stabilize TP53 and impair the growth and differentiation of erythroid cells. In contrast, ribosomes incorporating the missense variant erroneously read through UAG and UGA stop codons of mRNAs. Metabolic profiles of cells carrying the 5'UTR variant reveal an increased metabolism of amino acids and a switch from glycolysis to gluconeogenesis while those of cells carrying the missense variant reveal a depletion of nucleotide pools. These findings indicate that variants in the same RP gene can drive similar ribosome biogenesis defects yet still have markedly different downstream consequences and clinical impacts

Human health risk assessment for aluminium, aluminium oxide, and aluminium hydroxide.

International audienc