Showing papers by "Rehan Akbani published in 2011"

Integrated genomic analyses of ovarian carcinoma

Abstract: A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.

Integrated genomic analyses of ovarian carcinoma

Abstract: A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.

Enhancing role-based trust management with a reputation system for MANETs

Abstract: We start with role-based trust management (RBTM) and address some of the challenges associated with using RBTM in mobile ad hoc networks (MANETs). We then enhance RBTM with reputation systems (RSs), and propose a new hybrid trust management system (HTMS). In HTMS, the privilege level of an entity is determined not only by its role in the system, but also by its reputation score, which in turn is based on its behavior. If a privileged node becomes compromised and conducts several malicious or risky transactions, then its privilege level is quickly reduced to limit its access to resources and minimize the damage it can inflict further. The system uses a global, network-wide perspective to thwart global attacks. Such fine-grained variations of access control and dynamically assigning privilege levels would be very difficult to accomplish manually. We evaluated HTMS by comparing an implementation of it against an ideal response. We show that HTMS performs very close to the ideal if we can accurately estimate the proportion of malicious nodes in the network. We suggest using sampling to estimate this proportion. However, even if this estimate is not accurate, the results are still much better than using RBTM by itself. EDICS: SYS-ARCH; SYS-PROT; FOR-DETE; SYS-INTR.