Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes.

We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival.

Multifocal endometriotic lesions associated with cancer are clonal and carry a high mutation burden.

Endometriosis is a significant risk factor for clear cell and endometrioid ovarian cancers and is often found contiguous with these cancers. Using whole-genome shotgun sequencing of seven clear cell ovarian carcinomas (CCC) and targeted sequencing in synchronous endometriosis, we have investigated how this carcinoma may evolve from endometriosis. In every case we observed multiple tumour-associated somatic mutations in at least one concurrent endometriotic lesion.

Comparative analysis of resistant and susceptible macrophage gene expression response to Leishmania major parasite.

Background: Leishmania are obligated intracellular pathogens that replicate almost exclusively in macrophages. The outcome of infection depends largely on parasite pathogenicity and virulence but also on the activation status and genetic background of macrophages. Animal models are essential for a better understanding of pathogenesis of different microbes including Leishmania.

Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers.

Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using ∼100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity.

Issues in bioinformatics benchmarking: the case study of multiple sequence alignment.

The post-genomic era presents many new challenges for the field of bioinformatics. Novel computational approaches are now being developed to handle the large, complex and noisy datasets produced by high throughput technologies. Objective evaluation of these methods is essential (i) to assure high quality, (ii) to identify strong and weak points of the algorithms, (iii) to measure the improvements introduced by new methods and (iv) to enable non-specialists to choose an appropriate tool.

AlexSys: a knowledge-based expert system for multiple sequence alignment construction and analysis.

Multiple sequence alignment (MSA) is a cornerstone of modern molecular biology and represents a unique means of investigating the patterns of conservation and diversity in complex biological systems. Many different algorithms have been developed to construct MSAs, but previous studies have shown that no single aligner consistently outperforms the rest. This has led to the development of a number of 'meta-methods' that systematically run several aligners and merge the output into one single solution.

Optimization of extracellular xylanase production by Sclerotinia sclerotiorum S2 using factorial design.

The improvement of xylanase production by Sclerotinia sclerotiorum S2 using a liquid fermentation culture was investigated. The optimized process was divided into three basic steps: (i) evaluating xylanase inducers using different agricultural residues such as wheat bran, oat bran, orange peel and barley bran at 1% final concentration, and also filter paper. Among these, wheat bran showed the maximum activity (2.

Knowledge-based expert systems and a proof-of-concept case study for multiple sequence alignment construction and analysis.

The traditional approach to bioinformatics analyses relies on independent task-specific services and applications, using different input and output formats, often idiosyncratic, and frequently not designed to inter-operate. In general, such analyses were performed by experts who manually verified the results obtained at each step in the process. Today, the amount of bioinformatics information continuously being produced means that handling the various applications used to study this information presents a major data management and analysis challenge to researchers.

Electrostatic interactions of peptides flanking the tyrosine kinase domain in the epidermal growth factor receptor provides a model for intracellular dimerization and autophosphorylation.

The mechanism by which ligand-activated EGFR induces autophosphorylation via dimerization is not fully understood. Structural studies have revealed an extracellular loop mediated receptor dimerization. We have previously presented experimental data showing the involvement of a positive 13 amino acid peptide (R645-R657; P13+) from the intracellular juxtamembrane domain (JM) of EGFR important for intracellular dimerization and autophosphorylation.