Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Clinical utility of genetic tests for inherited hypertrophic and dilated cardiomyopathies

<p>Abstract</p> <p>Genetic testing has become an increasingly important part of medical practice for heritable form of cardiomyopathies. Hypertrophic cardiomyopathy and about 50% of idiopathic dilatative cardiomyopathy are familial diseases, with an autosomal dominant pattern of inheritance.</p> <p>Some genotype-phenotype correlations can provide important information to target DNA analyses in specific genes. Genetic testing may clarify diagnosis and help the optimal treatment strategies for more malignant phenotypes. In addition, genetic screening of first-degree relatives can help early identification and diagnosis of individuals at greatest risk for developing cardiomyopathy, allowing to focus clinical resources on high-risk family members.</p> <p>This paper provides a concise overview of the genetic etiology as well as the clinical utilities and limitations of genetic testing for the heritable cardiomyopathies.</p

Ancestral Pueblo Archaeology: The Value of Synthesis

Archaeologists working in the Ancestral Pueblo region of the American Southwest have documented variability in sociopolitical and economic complexity, landscape use, community organization, mobility, and violence at a wide range of temporal and spatial scales from AD 500-1700. Recent studies have a strong synthetic orientation, employ methods that track material culture, mobility, and social networks at macroregional scales, and benefit from a renewed engagement with indigenous peoples. Much of this research relies on integrating vast amounts of data from numerous academic and cultural resource management projects and demonstrates the promise of an archaeology that relies on the cumulative acquisition and sharing of data. Given the scale and depth of this research, Ancestral Pueblo archaeology is an exceptional comparative case for archaeologists considering similar processes, especially at fine temporal and wide geographical scales, in ancient farming societies across the globe