Carla Al Assaf

Analysis of phenotype and outcome in essential thrombocythemia with CALR or JAK2 mutations

The JAK2 V617F mutation, the thrombopoietin receptor MPL W515K/L mutation and calreticulin (CALR) mutations are mutually exclusive in essential thrombocythemia and support a novel molecular categorization of essential thrombocythemia. CALR mutations account for approximately 30% of cases of essential thrombocythemia. In a retrospective study, we examined the frequency of MPL and CALR mutations in JAK2 V617F-negative cases of essential thrombocythemia (n=103). In addition, we compared the clinical phenotype and outcome of CALR mutant cases of essential thrombocythemia with a cohort of JAK2 V617F-positive essential thrombocythemia (n=57). CALR-positive cases represented 63.7% of double-negative cases of essential thrombocythemia, and most carried CALR type 1 or type 2 indels. However, we also identified one patient who was positive for both the JAK2 V617F and the CALR mutations. This study revealed that CALR mutant essential thrombocythemia is associated with younger age, higher platelet counts, lower erythrocyte counts, leukocyte counts, hemoglobin, and hematocrit, and increased risk of progression to myelofibrosis in comparison with JAK2 V617F-positive essential thrombocythemia. Analysis of the CALR mutant group according to indel type showed that CALR type 1 deletion is strongly associated with male gender. CALR mutant patients had a better overall survival than JAK2 V617F-positive patients, in particular patients of age 60 years or younger. In conclusion, this study in a Belgian cohort of patients supports and extends the growing body of evidence that CALR mutant cases of essential thrombocythemia are phenotypically distinct from JAK2 V617F-positive cases, with regards to clinical and hematologic presentation as well as overall survival.

I-PV: a CIRCOS module for interactive protein sequence visualization

SUMMARY Todays genome browsers and protein databanks supply vast amounts of information about proteins. The challenge is to concisely bring together this information in an interactive and easy to generate format. AVAILABILITY AND IMPLEMENTATION We have developed an interactive CIRCOS module called i-PV to visualize user supplied protein sequence, conservation and SNV data in a live presentable format. I-PV can be downloaded from http://www.i-pv.org. CONTACT ibrahim.tanyalcin@i-pv.org, itanyalc@vub.ac.be or support@i-pv.org SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

Lexicon Visualization Library and JavaScript for Scientific Data Visualization

It’s becoming increasingly challenging to efficiently visualize and extract useful insight from complex and big data sets. JavaScript stands out as a suitable programming choice that offers mature libraries, easy implementation, and extensive customization, all of which stay in the shadow of new and rapid developments in the language. To illustrate the use of JavaScript in a scientific context, this article elaborates on Lexicon, a collection of JavaScript libraries for generating interactive visualizations in bioinformatics and other custom libraries.

Indoril: An I-PV Add-On For Visualization Of Point Mutations On 3D Cartesian Coordinates

Summary One of the main goals of proteomics is to understand how point mutations impact on the protein structure. Visualization and clustering of point mutations on user-defined 3 dimensional space can allow researchers to have new insights and hypothesis about the mutation’s mechanism of action. Availability and Implementation We have developed an interactive I-PV add-on called INDORIL to visualize point mutations. Indoril can be downloaded from http://www.i-pv.org. Contact ibrahim.tanyalcin@i-pv.org ║ support@i-pv.org Supplementary Information Please refer to the supplementary section and http://www.i-pv.org.

Convert your favorite protein modeling program into a mutation predictor: "MODICT".

BackgroundPredict whether a mutation is deleterious based on the custom 3D model of a protein.ResultsWe have developed modict, a mutation prediction tool which is based on per residue rmsd (root mean square deviation) values of superimposed 3D protein models. Our mathematical algorithm was tested for 42 described mutations in multiple genes including renin (REN), beta-tubulin (TUBB2B), biotinidase (BTD), sphingomyelin phosphodiesterase-1 (SMPD1), phenylalanine hydroxylase (PAH) and medium chain Acyl-Coa dehydrogenase (ACADM). Moreover, modict scores corresponded to experimentally verified residual enzyme activities in mutated biotinidase, phenylalanine hydroxylase and medium chain Acyl-CoA dehydrogenase. Several commercially available prediction algorithms were tested and results were compared. The modictperl package and the manual can be downloaded from https://github.com/IbrahimTanyalcin/MODICT.ConclusionsWe show here that modict is capable tool for mutation effect prediction at the protein level, using superimposed 3D protein models instead of sequence based algorithms used by polyphen and sift.