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31.
Applications of a new subspace clustering algorithm (COSA) in medical systems biology 总被引:1,自引:0,他引:1
Doris Damian Matej Orešič Elwin Verheij Jacqueline Meulman Jerome Friedman Aram Adourian Nicole Morel Age Smilde Jan van der Greef 《Metabolomics : Official journal of the Metabolomic Society》2007,3(1):69-77
A novel clustering approach named Clustering Objects on Subsets of Attributes (COSA) has been proposed (Friedman and Meulman,
(2004). Clustering objects on subsets of attributes. J. R. Statist. Soc. B 66, 1–25.) for unsupervised analysis of complex data sets. We demonstrate its usefulness in medical systems biology studies.
Examples of metabolomics analyses are described as well as the unsupervised clustering based on the study of disease pathology
and intervention effects in rats and humans. In comparison to principal components analysis and hierarchical clustering based
on Euclidean distance, COSA shows an enhanced capability to trace partial similarities in groups of objects enabling a new
discovery approach in systems biology as well as offering a unique approach to reveal common denominators of complex multi-factorial
diseases in animal and human studies.
Doris Damian, Matej Orešič, and Elwin Verheij contributed equally to this work. 相似文献
32.
Pshezhetsky AV Fedjaev M Ashmarina L Mazur A Budman L Sinnett D Labuda D Beaulieu JF Ménard D Nifant'ev I Levy E 《Proteomics》2007,7(13):2201-2215
Human colorectal carcinoma (Caco-2) cells undergo in culture spontaneous enterocytic differentiation, characterized by polarization and appearance of the functional apical brush border membrane. To provide insights into the biology of differentiation, we have performed a comparative proteomic analysis of the plasma membranes from proliferating cells (PCs) and the apical membranes from differentiated cells (DCs). Proteins were resolved by SDS-PAGE, in-gel digested and analyzed by RP-LC and MS/MS. Alternatively, proteins were digested in solution, and tryptic peptides were labeled with isotopic tags and analyzed by 2-D LC followed by MS/MS. Among the 1125 proteins identified in both proteomes, 76 were found to be significantly increased in the membranes of DCs and 61 were increased in PCs. Majority of the proteins increased in the apical membranes were metabolic enzymes, proteins involved in the maintenance of cellular structure, transmembrane transporters, and proteins regulating vesicular transport. In contrast, majority of the proteins increased in the membranes of PCs were involved in gene expression, protein synthesis, and folding. Both groups contained many novel proteins with yet to be identified functions, which could provide potential new markers of the intestinal cells or of colorectal cancer. 相似文献
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34.
Damian Bartuzi Agnieszka A. Kaczor Dariusz Matosiuk 《Journal of biomolecular structure & dynamics》2019,37(1):36-47
Allostery is one of the most important features of proteins. It greatly contributes to the complexity of life, since it enables possibility of precise tuning of protein function, as well as performing more than one function per protein. Probe dependence is one of the unique features of allostery. It allows a protein to respond differently to the same allosteric modulator when different drugs or transmitters are bound. Unfortunately, allosteric mechanisms are difficult to investigate experimentally. Instead, they can be reproduced artificially in simulations. We simulated in silico a native-like cell membrane fragment with an active-state human μ opioid receptor (MOR) in order to investigate diverse effects of a receptor’s positive allosteric modulator on various agonists. Particular emphasis on native-likeness of the environment was put. We managed to reproduce the experimentally observed effects, which allowed us to take deeper insight into their underlying mechanisms. We found an allosteric pathway in the receptor, leading from the ligand binding site to the intracellular, effector site. We observed that the modulator affected the pathway, inducing different resultant responses for full and partial agonists. 相似文献
35.
Jakub Marynowicz Mateusz Lango Damian Horna Karol Kikut Marcin Andrzejewski 《Biology of sport / Institute of Sport》2022,39(2):245
The purpose of this study was to determine the effectiveness of white-box decision tree models (DTM) for predicting the rating of perceived exertion (RPE). The second aim was to examine the relationship between RPE and external measures of intensity in youth soccer training at the group and individual level. Training load data from 18 youth soccer players were collected during an in-season competition period. A total of 804 training observations were undertaken, with a total of 43 ± 17 sessions per player (range 12–76). External measures of intensity were determined using a 10 Hz GPS and included total distance (TD, m/min), high-speed running distance (HSR, m/min), PlayerLoad (PL, n/min), impacts (n/min), distance in acceleration/deceleration (TD ACC/TD DEC, m/min) and the number of accelerations/decelerations (ACC/DEC, n/min). Data were analysed with decision tree models. Global and individualized models were constructed. Aggregated importance revealed HSR as the strongest predictor of RPE with relative importance of 0.61. HSR was the most important factor in predicting RPE for half of the players. The prediction error (root mean square error [RMSE] 0.755 ± 0.014) for the individualized models was lower compared to the population model (RMSE 1.621 ± 0.001). The findings demonstrate that individual models should be used for the assessment of players’ response to external load. Furthermore, the study demonstrates that DTM provide straightforward interpretation, with the possibility of visualization. This method can be used to prescribe daily training loads on the basis of predicted, desired player responses (exertion). 相似文献
36.
Morales-Montor J Baig S Mitchell R Deway K Hallal-Calleros C Damian RT 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(8):4527-4533
Taenia crassiceps cysticercosis results in an impressive feminization in male mice during chronic infection, characterized by increased serum estradiol levels 100 times their normal values, while those of testosterone and dihydrotestosterone are decreased by 85 and 95% respectively. Concomitantly, the levels of follicle-stimulating hormone and IL-6 are increased 70 and 90 times their normal values in the infected male mice. Since a specific Th1/Th2 shift of the immune response has been previously reported during the chronic infection, and this shift may be associated with the feminization process, we proposed that this shift is induced by immunoendocrine interactions during the disease, and this gives way to a change in the initial resistance to the infection in the male mice, which become as susceptible as female mice. To confirm this hypothesis, we depleted immune system activity in two different ways: total body irradiation and neonatal thymectomy. Our results show that when immune system activity is depleted using either strategy, the male mice do not feminize, and the levels of follicle-stimulating hormone and IL-6 are inhibited. Depletion of IL-6 using IL-6(-/-) knockout mice does not produce the feminization process stated above, while restitution of the IL-6(-/-) knockout, irradiated, and thymectomized mice with murine recombinant IL-6 restores the feminization process. Expression of the IL-6 gene was found only in the testes and spleen of infected animals. Our results illustrate the importance of immunoendocrine interactions during a parasitic disease and show a possible new mechanism of parasite establishment in an initially resistant host. 相似文献
37.
Counsell D 《Comparative and Functional Genomics》2004,5(6-7):480-490
This April, in Cambridge (UK), principal investigators from the Mathematical Biology Group of the Medical Research Council's National Institute of Medical Research organized a workshop in structural bioinformatics at the Centre for Mathematical Sciences. Bioinformatics researchers of several nationalities from labs around the country presented and discussed their computational work in biomolecular structure prediction and analysis, and in protein evolution. The meeting was intensive and lively and gave attendees an overview of the healthy state of protein bioinformatics in the UK. 相似文献
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39.
Nematogens and vermiform embryos of a new species of Dicyema are described from an octopus collected off Veracruz, Mexico. Dicyema shorti n. sp. is a small dicyemid species that rarely exceeds 500 microm in length. It is further characterized by the presence of 18 peripheral cells in the vermiform stages, a conical-shape calotte, and an axial cell that extends to the base of the propolar cells. Other stages in the life cycle of the parasite are not known. This is the first dicyemid to be described from Octopus burryi Voss. 1950, and also from both the southern Gulf of Mexico and the country of Mexico. 相似文献
40.
Surnames and non-recombining alleles are inherited from a single parent in a highly similar way. A simple birth-death model with mutations can accurately describe this process. Exponentially growing and constant populations are investigated, and we study how different compositions of the founder populations can be observed in present-day diversity distributions. We analyse different quantities in the statistically stationary state, both through analytic and numerical methods. Our results compare favourably to field data for family sizes in several countries. We discuss the relationship between the distribution of surnames and the genetic diversity of a population. 相似文献