Colon cancer associated genes exhibit signatures of positive selection at functionally significant positions.

BACKGROUND: Cancer, much like most human disease, is routinely studied by utilizing model organisms. Of these model organisms, mice are often dominant. However, our assumptions of functional equivalence fail to consider the opportunity for divergence conferred by ~180 Million Years (MY) of independent evolution between these species. For a given set of human disease related genes, it is therefore important to determine if functional equivalency has been retained between species. In this study we test the hypothesis that cancer associated genes have different patterns of substitution akin to adaptive evolution in different mammal lineages. RESULTS: Our analysis of the current literature and colon cancer databases identified 22 genes exhibiting colon cancer associated germline mutations. We identified orthologs for these 22 genes across a set of high coverage (>6X) vertebrate genomes. Analysis of these orthologous datasets revealed significant levels of positive selection. Evidence of lineage-specific positive selection was identified in 14 genes in both ancestral and extant lineages. Lineage-specific positive selection was detected in the ancestral Euarchontoglires and Hominidae lineages for STK11, in the ancestral primate lineage for CDH1, in the ancestral Murinae lineage for both SDHC and MSH6 genes and the ancestral Muridae lineage for TSC1. CONCLUSION: Identifying positive selection in the Primate, Hominidae, Muridae and Murinae lineages suggests an ancestral functional shift in these genes between the rodent and primate lineages. Analyses such as this, combining evolutionary theory and predictions - along with medically relevant data, can thus provide us with important clues for modeling human diseases.

The landscape for epigenetic/epigenomic biomedical resources.

Recent advances in molecular biology and computational power have seen the biomedical sector enter a new era, with corresponding development of Bioinformatics as a major discipline. Generation of enormous amounts of data has driven the need for more advanced storage solutions and shared access through a range of public repositories. The number of such biomedical resources is increasing constantly and mining these large and diverse data sets continues to present real challenges. This paper attempts a general overview of currently available resources, together with remarks on their data mining and analysis capabilities. Of interest here is the recent shift in focus from genetic to epigenetic/epigenomic research and the emergence and extension of resource provision to support this both at local and global scale. Biomedical text and numerical data mining are both considered, the first dealing with automated methods for analyzing research content and information extraction, and the second (broadly) with pattern recognition and prediction. Any summary and selection of resources is inherently limited, given the spectrum available, but the aim is to provide a guideline for the assessment and comparison of currently available provision, particularly as this relates to epigenetics/epigenomics.

Design and implementation of an end tidal CO2 simulator for the evaluation of clinical gas analysers.

This paper presents a new technique to determine the dynamic and frequency response of capnographs using a custom built 'EtCO2 simulator system'. Capnographs are devices that use CO2 from a patients' expired breath to monitor the cardiopulmonary status during anaesthesia and mechanical ventilation. Capnographs at present are routinely calibrated via a static calibration method only. The dynamic response of the capnographs is not accounted for. The frequency and time response are important as they determine if capnographs can be used in high frequency and pediatric ventilation schemes. Experiments performed using the method described in this paper proved that old capnographs usually do not satisfy the manufacturer quoted specifications for time and frequency response. Therefore, a routine check for capnographs is recommended. The method can also be used to verify manufacturer quoted specifications. The EtCO2 simulator system, designed and constructed simulates human respiration cycle. The gas sources used are 5% CO2 and room air that can be switched alternatively. Both supplies are pressure regulated and connected through non-return valves to electric valves. The valves are microprocessor controlled and the on/off time is user defined allowing a wide range of waveforms to be simulated. The output from the simulator is delivered to capnograph. Capnograms are captured by digital video recording. The captured video in 'avi' file format is then converted into individual frames. These frames are converted into digital data through image processing in Matlab. The data obtained is subjected to extensive analysis to determine the frequency and time response of the respective capnograph.