Retroviral Integration Mutagenesis in Mice and Comparative Analysis in Human AML Identify Reduced PTP4A3 Expression as a Prognostic Indicator

Acute myeloid leukemia (AML) results from multiple genetic and epigenetic aberrations, many of which remain unidentified. Frequent loss of large chromosomal regions marks haplo-insufficiency as one of the major mechanisms contributing to leukemogenesis. However, which haplo-insufficient genes (HIGs) are involved in leukemogenesis is largely unknown and powerful experimental strategies aimed at their identification are currently lacking. Here, we present a new approach to discover HIGs, using retroviral integration mutagenesis in mice in which methylated viral integration sites and neighbouring genes were identified. In total we mapped 6 genes which are flanked by methylated viral integration sites (mVIS). Three of these, i.e., Lrmp, Hcls1 and Prkrir, were up regulated and one, i.e., Ptp4a3, was down regulated in the affected tumor. Next, we investigated the role of PTP4A3 in human AML and we show that PTP4A3 expression is a negative prognostic indicator, independent of other prognostic parameters. In conclusion, our novel strategy has identified PTP4A3 to potentially have a role in AML, on one hand as a candidate HIG contributing to leukemogenesis in mice and on the other hand as a prognostic indicator in human AML

Exome Sequencing Reveals Comprehensive Genomic Alterations across Eight Cancer Cell Lines

It is well established that genomic alterations play an essential role in oncogenesis, disease progression, and response of tumors to therapeutic intervention. The advances of next-generation sequencing technologies (NGS) provide unprecedented capabilities to scan genomes for changes such as mutations, deletions, and alterations of chromosomal copy number. However, the cost of full-genome sequencing still prevents the routine application of NGS in many areas. Capturing and sequencing the coding exons of genes (the “exome”) can be a cost-effective approach for identifying changes that result in alteration of protein sequences. We applied an exome-sequencing technology (Roche Nimblegen capture paired with 454 sequencing) to identify sequence variation and mutations in eight commonly used cancer cell lines from a variety of tissue origins (A2780, A549, Colo205, GTL16, NCI-H661, MDA-MB468, PC3, and RD). We showed that this technology can accurately identify sequence variation, providing ∼95% concordance with Affymetrix SNP Array 6.0 performed on the same cell lines. Furthermore, we detected 19 of the 21 mutations reported in Sanger COSMIC database for these cell lines. We identified an average of 2,779 potential novel sequence variations/mutations per cell line, of which 1,904 were non-synonymous. Many non-synonymous changes were identified in kinases and known cancer-related genes. In addition we confirmed that the read-depth of exome sequence data can be used to estimate high-level gene amplifications and identify homologous deletions. In summary, we demonstrate that exome sequencing can be a reliable and cost-effective way for identifying alterations in cancer genomes, and we have generated a comprehensive catalogue of genomic alterations in coding regions of eight cancer cell lines. These findings could provide important insights into cancer pathways and mechanisms of resistance to anti-cancer therapies

Information and Arena: The Dual Function of the News Media for Political Elites

Abstract: How do individual politicians use the news media to reach their political goals? This study addresses the question by proposing an actor-centered, functional approach. We distinguish 2 essential functions (and subfunctions) the mass media have for political elites. The media are a source of information; politicians depend on it for pure information and they can profit from the momentum generated by media information. The media also are an arena elites need access to in order to promote themselves and their issues. These 2 functions offer certain politicians a structural advantage over others and, hence, are relevant for the power struggle among political elites. A systematic functional account enables comparisons of the role of the media across politicians and political systems

Bioinformatics and systems biology research update from the 15th International Conference on Bioinformatics (InCoB2016)

The International Conference on Bioinformatics (InCoB) has been publishing peer-reviewed conference papers in BMC Bioinformatics since 2006. Of the 44 articles accepted for publication in supplement issues of BMC Bioinformatics, BMC Genomics, BMC Medical Genomics and BMC Systems Biology, 24 articles with a bioinformatics or systems biology focus are reviewed in this editorial. InCoB2017 is scheduled to be held in Shenzen, China, September 20-22, 2017.4 page(s

2016 update on APBioNet's annual international conference on bioinformatics (InCoB)

InCoB became since its inception in 2002 one of the largest annual bioinformatics conferences in the Asia-Pacific region with attendance ranging between 150 and 250 delegates depending on the venue location. InCoB 2016 in Singapore was attended by almost 220 delegates. This year, sessions on structural bioinformatics, sequence and sequencing, and next-generation sequencing fielded the highest number of oral presentation. Forty-four out 96 oral presentations were associated with an accepted manuscript in supplemental issues of BMC Bioinformatics, BMC Genomics, BMC Medical Genomics or BMC Systems Biology. Articles with a genomics focus are reviewed in this editorial. Next year's InCoB will be held in Shenzen, China from September 20 to 22, 2017.4 page(s