Cytosine Methyltransferases as Tumor Markers

Changes in DNA methylation patterns is a prominent characteristic of human tumors. Tumor cells display reduced levels of genomic DNA methylation and site-specific CpG island hypermethylation. Methylation of CpG dinucleotides is catalyzed by the enzyme family of DNA methyltransferases (DNMTs). In this review, the role of DNA methylation and DNMTs as key determinants of carcinogenesis is further elucidated. The chromatin modifying proteins that are known to interact with DNMTs are also described. Finally, the role of DNMTs as potential therapeutic targets is addressed

Protein signatures using electrostatic molecular surfaces in harmonic space

We developed a novel method based on the Fourier analysis of protein molecular surfaces to speed up the analysis of the vast structural data generated in the post-genomic era. This method computes the power spectrum of surfaces of the molecular electrostatic potential, whose three-dimensional coordinates have been either experimentally or theoretically determined. Thus we achieve a reduction of the initial three-dimensional information on the molecular surface to the one-dimensional information on pairs of points at a fixed scale apart. Consequently, the similarity search in our method is computationally less demanding and significantly faster than shape comparison methods. As proof of principle, we applied our method to a training set of viral proteins that are involved in major diseases such as Hepatitis C, Dengue fever, Yellow fever, Bovine viral diarrhea and West Nile fever. The training set contains proteins of four different protein families, as well as a mammalian representative enzyme. We found that the power spectrum successfully assigns a unique signature to each protein included in our training set, thus providing a direct probe of functional similarity among proteins. The results agree with established biological data from conventional structural biochemistry analyses.Comment: 9 pages, 10 figures Published in PeerJ (2013), https://peerj.com/articles/185

AmalgamScope: merging annotations data across the human genome

The past years have shown an enormous advancement in sequencing and array-based technologies, producing supplementary or alternative views of the genome stored in various formats and databases. Their sheer volume and different data scope pose a challenge to jointly visualize and integrate diverse data types. We present AmalgamScope a new interactive software tool focusing on assisting scientists with the annotation of the human genome and particularly the integration of the annotation files from multiple data types, using gene identifiers and genomic coordinates. Supported platforms include next-generation sequencing and microarray technologies. The available features of AmalgamScope range from the annotation of diverse data types across the human genome to integration of the data based on the annotational information and visualization of the merged files within chromosomal regions or the whole genome. Additionally, users can define custom transcriptome library files for any species and use the file exchanging distant server options of the tool

Insights into the structure and 3D spatial arrangement of the b-ketoacyl carrier protein synthases

The b-ketoacyl carrier protein synthases (the KAS enzymes) are key enzymes that can be used as potential anti-Plasmodium drug targets. In bacteria, three KAS enzymes have been identified (KAS I, KAS II and KAS III), whilst in Plasmodium a KAS I/II and KAS III enzyme has been reported. The protein has a total of four active sites, which have been found to be different to each other, rather than four copies of the same active site. The active sites differ not only in the type of interaction they establish with the ligand, but, in the case of Cerulenin as a ligand, the active sites of the KAS I/II enzyme also differ in the number of residues involved in the ligand protein interaction. This is very interesting biochemically, because these differences imply that the affinity of each active site for binding to the ligand might be different as well.  

Current viral infections and epidemics of flaviviridae; lots of grief but also some hope

Flaviviridae is a family of RNA viruses that includes numerous important human and animal pathogens. Recent studies on subgenomic flaviviridae replicons have revealed that the non-structural (NS) proteins, which are encoded by the C-terminal part of the polyprotein, play a crucial role in viral RNA replication. Accordingly, these proteins are assumed to form replication complexes in conjunction with genomic RNA and possibly with other cellular factors. One the most important non-structural enzymes that plays a key role in the life cycle of flaviviridae viruses is the viral helicase. Sequence alignments of the viral helicases from this family identified several conserved sequence motifs that are important for biological functions. Herein, an effort is made to summarize the current epidemics associated with the flaviviridae family worldwide, the potential of helicase enzymes as a promising pharmacological target and the use of nucleoside analogs as simple, efficient and rather versatile antiviral agents

Phylogenetic and regulatory region analysis of Wnt5 genes reveals conservation of a regulatory module with putative implication in pancreas development

<p>Abstract</p> <p>Background</p> <p><it>Wnt5 </it>genes belong to the large <it>Wnt </it>family, encoding proteins implicated into several tumorigenic and developmental processes. Phylogenetic analyses showed that <it>Wnt5 </it>gene has been duplicated at the divergence time of gnathostomata from agnatha. Interestingly, experimental data for some species indicated that only one of the two <it>Wnt5 </it>paralogs participates in the development of the endocrine pancreas. The purpose of this paper is to reexamine the phylogenetic history of the Wnt5 developmental regulators and investigate the functional shift between paralogs through comparative genomics.</p> <p>Results</p> <p>In this study, the phylogeny of <it>Wnt5 </it>genes was investigated in species belonging to <it>protostomia </it>and <it>deuterostomia</it>. Furthermore, an <it>in silico </it>regulatory region analysis of <it>Wnt5 </it>paralogs was conducted, limited to those species with insulin producing cells and pancreas, covering the evolutionary distance from agnatha to gnathostomata. Our results confirmed the <it>Wnt5 </it>gene duplication and additionally revealed that this duplication event included also the upstream region. Moreover, within this latter region, a conserved module was detected to which a complex of transcription factors, known to be implicated in embryonic pancreas formation, bind.</p> <p>Conclusions</p> <p>Results and observations presented in this study, allow us to conclude that during evolution, the <it>Wnt5 </it>gene has been duplicated in early vertebrates, and that some paralogs conserved a module within their regulatory region, functionally related to embryonic development of pancreas. Interestingly, our results allowed advancing a possible explanation on why the <it>Wnt5 </it>orthologs do not share the same function during pancreas development. As a final remark, we suggest that an <it>in silico </it>comparative analysis of regulatory regions, especially when associated to published experimental data, represents a powerful approach for explaining shift of roles among paralogs.</p> <p>Reviewers</p> <p>This article was reviewed by Sarath Janga (nominated by Sarah Teichmann), Ran Kafri (nominated by Yitzhak Pilpel), and Andrey Mironov (nominated by Mikhail Gelfand).</p