Identification of novel targets for breast cancer by exploring gene switches on a genome scale

<p>Abstract</p> <p>Background</p> <p>An important feature that emerges from analyzing gene regulatory networks is the "switch-like behavior" or "bistability", a dynamic feature of a particular gene to preferentially toggle between two steady-states. The state of gene switches plays pivotal roles in cell fate decision, but identifying switches has been difficult. Therefore a challenge confronting the field is to be able to systematically identify gene switches.</p> <p>Results</p> <p>We propose a top-down mining approach to exploring gene switches on a genome-scale level. Theoretical analysis, proof-of-concept examples, and experimental studies demonstrate the ability of our mining approach to identify bistable genes by sampling across a variety of different conditions. Applying the approach to human breast cancer data identified genes that show bimodality within the cancer samples, such as estrogen receptor (ER) and ERBB2, as well as genes that show bimodality between cancer and non-cancer samples, where tumor-associated calcium signal transducer 2 (TACSTD2) is uncovered. We further suggest a likely transcription factor that regulates TACSTD2.</p> <p>Conclusions</p> <p>Our mining approach demonstrates that one can capitalize on genome-wide expression profiling to capture dynamic properties of a complex network. To the best of our knowledge, this is the first attempt in applying mining approaches to explore gene switches on a genome-scale, and the identification of TACSTD2 demonstrates that single cell-level bistability can be predicted from microarray data. Experimental confirmation of the computational results suggest TACSTD2 could be a potential biomarker and attractive candidate for drug therapy against both ER+ and ER- subtypes of breast cancer, including the triple negative subtype.</p

Analysis of genome-wide DNA arrays reveals the genomic population structure and diversity in autochthonous Greek goat breeds

Goats play an important role in the livestock sector in Greece. The national herd consists mainly of two indigenous breeds, the Eghoria and Skopelos. Here, we report the population structure and genomic profiles of these two native goat breeds using Illumina's Goat SNP50 BeadChip. Moreover, we present a panel of candidate markers acquired using different genetic models for breed discrimination. Quality control on the initial dataset resulted in 48,841 SNPs kept for downstream analysis. Principal component and admixture analyses were applied to assess population structure. The rate of inbreeding within breed was evaluated based on the distribution of runs of homozygosity in the genome and respective coefficients, the genomic relationship matrix, the patterns of linkage disequilibrium, and the historic effective population size. Results showed that both breeds exhibit high levels of genetic diversity. Level of inbreeding between the two breeds estimated by the Wright's fixation index FST was low (Fst = 0.04362), indicating the existence of a weak genetic differentiation between them. In addition, grouping of farms according to their geographical locations was observed. This study presents for the first time a genome-based analysis on the genetic structure of the two indigenous Greek goat breeds and identifies markers that can be potentially exploited in future selective breeding programs for traceability purposes, targeted genetic improvement schemes and conservation strategies

Cloud-to-ground lightning observations over the eastern Amazon Region

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Cloud-to-ground (CG) lightning variables, space and time distributions near the equator, over Eastern Amazon, were analyzed in this work. Over seven million lightning flash events of this type, detected by a VAISALA lightning detection network were processed. This data set was collected by the Brazilian Amazon Protection System between 2006 and 2008. The results showed the sub-areas of higher occurrence densities, polarity types, current peak intensity intervals, as well as, the hourly distributions of CG lightning, for this region. A considerable percentage (7%) of discharges with stroke current peaks above 100 kA, was observed. An attempt was made to compare the statistical results of this work with observations made elsewhere in Brazil and other regions of the world. The differences found suggest that, some regional peculiarities of the CG lightning parameter values should be taken into consideration, for electric and telecommunication systems protection against atmospheric electric discharges, in the Amazon Region. (C) 2011 Elsevier B.V. All rights reserved.117SI8690Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financier of Studies and Projects (FINEP) - REMAM 2 ProjectConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq