UniProt-Related Documents (UniReD): assisting wet lab biologists in their quest on finding novel counterparts in a protein network.

The in-depth study of protein-protein interactions (PPIs) is of key importance for understanding how cells operate. Therefore, in the past few years, many experimental as well as computational approaches have been developed for the identification and discovery of such interactions. Here, we present UniReD, a user-friendly, computational prediction tool which analyses biomedical literature in order to extract known protein associations and suggest undocumented ones. As a proof of concept, we demonstrate its usefulness by experimentally validating six predicted interactions and by benchmarking it against public databases of experimentally validated PPIs succeeding a high coverage. We believe that UniReD can become an important and intuitive resource for experimental biologists in their quest for finding novel associations within a protein network and a useful tool to complement experimental approaches (e.g. mass spectrometry) by producing sorted lists of candidate proteins for further experimental validation. UniReD is available at http://bioinformatics.med.uoc.gr/unired/

Visualizing the dynamics of histone variants in the S-phase nucleus

Abstract Histone variants constitute a fundamental feature of the epigenome. However, their dynamics during normal and challenged DNA replication and their distribution in the three-dimensional space of the nucleus remain poorly characterized. A recent study employed stochastic optical reconstruction microscopy (STORM) to obtain a high-resolution view of the spatial distribution of H3 histone variants in the nucleus and related this to the timing of DNA replication

In silico analysis of DNA re-replication across a complete genome reveals cell-to-cell heterogeneity and genome plasticity

DNA replication is a complex and remarkably robust process: despite its inherent uncertainty, manifested through stochastic replication timing at a single-cell level, multiple control mechanisms ensure its accurate and timely completion across a population. Disruptions in these mechanisms lead to DNA rereplication, closely connected to genomic instability and oncogenesis. Here, we present a stochastic hybrid model of DNA re-replication that accurately portrays the interplay between discrete dynamics, continuous dynamics and uncertainty. Using experimental data on the fission yeast genome, model simulations show how different regions respond to rereplication and permit insight into the key mechanisms affecting re-replication dynamics. Simulated and experimental population-level profiles exhibit a good correlation along the genome, robust to model parameters, validating our approach. At a single-cell level, copy numbers of individual loci are affected by intrinsic properties of each locus, in cis effects from adjoining loci and in trans effects from distant loci. In silico analysis and single-cell imaging reveal that cell-to-cell heterogeneity is inherent in re-replication and can lead to genome plasticity and a plethora of genotypic variations

Incidence and Prognosis of Clonal Hematopoiesis in patients with Chronic Idiopathic Neutropenia

The incidence and prognosis of clonal hematopoiesis in patients with isolated neutropenia among patients with idiopathic cytopenia of undetermined significance (ICUS), known as ICUS-N or chronic idiopathic neutropenia (CIN) patients, is poorly defined. In the present study we sought to investigate the frequency and clinical significance of mutations of genes implicated in myeloid malignancies using next generation sequencing, in CIN patients (n=185) with a long follow-up. We found that 21/185 patients (11.35%) carried totally 25 somatic mutations in 6 genes with median variant allele frequency (VAF) 12.75%. The most frequently mutated genes were DNMT3A and TET2 involving more than 80% of patients followed by IDH1/2, SRSF2 and ZRSR2. The frequency of transformation to a myeloid malignancy was low in the total group of patients (5/185 patients; 2.70%). However, from the transformed patients four belonged to the clonal (4/21; 19.05%) and one to the non-clonal (1/164; 0.61%) group, indicating that the presence of mutation(s) confers a relative risk for transformation 31.24 (P = 0.0017). The VAF of the mutant clones in the transformed patients was higher than 10% in all cases and the genes most frequently associated with malignant transformation were the SRSF2 and IDH1. No significant differences were identified between clonal and non-clonal groups in the severity of neutropenia. Patients with clonal disease were older compared to non-clonal patients. These data contribute to the better understanding of the heterogeneous entities underlying ICUS and highlight the importance of the mutation analysis for the diagnosis and prognosis of patients with unexplained neutropenias