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

Size variability of juvenile (0+yr) bay scallops Argopecten irradians irradians (Lamarck, 1819) at eight sites in eastern Long Island, New York

Volume: 44Start Page: 389End Page: 39

Restoration of Bay Scallop Populations and Fisheries in the Peconic Bays, New York

In 2006, we initiated an intensive restoration program to jump-start Peconic bay scallop populations which had been decimated by brown tide algal blooms from 1985-1995. As originally hypothesized, populations proved to be recruitment limited – as evidenced by order of magnitude increases in larval settlement following initiation of restoration. Modeled production of fertilized eggs from spawns of broodstock deployed at high densities (lantern nets on longlines, free-planting) accounted for significant proportions of calculated totals for respective embayments. Significant increases in natural, benthic populations were not seen immediately, but the size of the larval pool increased further as we continued and expanded restoration efforts. Then, natural populations began to rebuild throughout the Peconic Bays within a few years. Annual commercial scallop landings have increased by as much as 30x compared to average harvests for the 12 years prior to initiation of our restoration efforts. Increases in dockside revenues since 2008 have far exceeded the total spent on restoration. All lines of evidence confirm that restoration has driven the observed increases in populations and fishery landings. Sustained restoration efforts, at an appropriate scale, may be an effective strategy for increasing natural bay scallop population densities/sizes to threshold levels above which they become self-sustaining

Aspiring to an Altered Stable State: Rebuilding of Bay Scallop Populations and Fisheries Following Intensive Restoration

Intensive efforts to restore bay scallop Argopecten irradians irradians populations and fisheries in the Peconic Bays of eastern Long Island, New York, USA, were begun in 2006, following a 12 yr period during which commercial fishery landings averaged 1 to 2% of historical levels seen prior to 1985 to 1995 brown tide algal blooms. Compared to 2005 to 2006, natural population densities of 0+ yr scallops in fall increased 16× by 2007 in Orient Harbor (OH), the focus of our restoration efforts; by 2009, densities in OH and other, unplanted, embayments had increased by 110× and up to 331×, respectively. Spatial and temporal patterns paralleled those documented for larval recruitment; highly significant correlations between commercial harvest levels and both baywide larval settlement and juvenile benthic densities were revealed. Official fishery landings were 13× those of pre-restoration levels by 2010 and have remained relatively stable through 2013. Following commencement of restoration, dockside revenues and economic benefit to the regional economy have increased by ~US$2 million and$20 million, respectively; our calculations suggest that these figures are 40% of actual numbers. Population resurgence is not correlated to temporal changes in predator populations or submerged aquatic vegetation cover. We conclude that rebuilding of Peconic bay scallop populations and fisheries has been driven by dramatic increases in bay scallop larval supply emanating from our intensive restoration efforts. By definition, we cannot say that Peconic bay scallops have attained an alternate stable state, but it is clear that dramatic increases in populations, fishery landings, and economic value are possible in just a few years