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91.
Principal component models for sparse functional data 总被引:5,自引:0,他引:5
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Vinita Periwal Stefan Bassler Sergej Andrejev Natalia Gabrielli Kaustubh Raosaheb Patil Athanasios Typas Kiran Raosaheb Patil 《PLoS computational biology》2022,18(4)
Natural compounds constitute a rich resource of potential small molecule therapeutics. While experimental access to this resource is limited due to its vast diversity and difficulties in systematic purification, computational assessment of structural similarity with known therapeutic molecules offers a scalable approach. Here, we assessed functional similarity between natural compounds and approved drugs by combining multiple chemical similarity metrics and physicochemical properties using a machine-learning approach. We computed pairwise similarities between 1410 drugs for training classification models and used the drugs shared protein targets as class labels. The best performing models were random forest which gave an average area under the ROC of 0.9, Matthews correlation coefficient of 0.35, and F1 score of 0.33, suggesting that it captured the structure-activity relation well. The models were then used to predict protein targets of circa 11k natural compounds by comparing them with the drugs. This revealed therapeutic potential of several natural compounds, including those with support from previously published sources as well as those hitherto unexplored. We experimentally validated one of the predicted pair’s activities, viz., Cox-1 inhibition by 5-methoxysalicylic acid, a molecule commonly found in tea, herbs and spices. In contrast, another natural compound, 4-isopropylbenzoic acid, with the highest similarity score when considering most weighted similarity metric but not picked by our models, did not inhibit Cox-1. Our results demonstrate the utility of a machine-learning approach combining multiple chemical features for uncovering protein binding potential of natural compounds. 相似文献
94.
Marleen TJ van Ampting Arjan J Schonewille Carolien Vink Robert Jan M Brummer van der Roelof Meer Ingeborg MJ Bovee-Oudenhoven 《BMC physiology》2009,9(1):6-9
Background
Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal glutathione focus on oxidative stress reduction without considering functional disease outcome. Our aim was to determine whether depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation. 相似文献95.
T J Bassler 《BMJ (Clinical research ed.)》1977,1(6055):229-230
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Chemotaxis to chitin oligosaccharides by Vibrio furnissii, a chitinivorous marine bacterium 总被引:1,自引:0,他引:1
B Bassler P Gibbons S Roseman 《Biochemical and biophysical research communications》1989,161(3):1172-1176
We have reported that Vibrio furnissii, a chitinivorous marine bacterium, expresses a complex apparatus for adhesion/deadhesion to chitin analogues (1). In the present studies, we show that this organism exhibits a chemotactic response (swarming) to chitin oligosaccharides at concentrations as low as 10 microM. In contrast, V. furnissii exhibits slight to no chemotaxis to other utilizable compounds (glycerol, lactate, amino acids), with the exception of L-glutamic acid. V. furnissii may lack the tar (aspartate) receptor of Escherichia coli. 相似文献
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Type VI secretion is critical for Vibrio cholerae to successfully combat phagocytic eukaryotes and to survive in the presence of competing bacterial species. V. cholerae type VI secretion system genes are encoded in one large and two small clusters. In V. cholerae, type VI secretion is controlled by quorum sensing, the cell–cell communication process that enables bacteria to orchestrate group behaviours. The quorum‐sensing response regulator LuxO represses type VI secretion genes at low cell density and the quorum‐sensing regulator HapR activates type VI secretion genes at high cell density. We demonstrate that the quorum regulatory small RNAs (Qrr sRNAs) that function between LuxO and HapR in the quorum‐sensing cascade are required for these regulatory effects. The Qrr sRNAs control type VI secretion via two mechanisms: they repress expression of the large type VI secretion system cluster through base pairing and they repress HapR, the activator of the two small type VI secretion clusters. This regulatory arrangement ensures that the large cluster encoding many components of the secretory machine is expressed prior to the two small clusters that encode the secreted effectors. Qrr sRNA‐dependent regulation of the type VI secretion system is conserved in pandemic and non‐pandemic V. cholerae strains. 相似文献
100.
Katharina F. Mueller Matthias Briel Daniel Strech Joerg J. Meerpohl Britta Lang Edith Motschall Viktoria Gloy Francois Lamontagne Dirk Bassler 《PloS one》2014,9(12)