26 research outputs found
Products of gut microbial Toll/interleukin-1 receptor domain NADase activities in gnotobiotic mice and Bangladeshi children with malnutrition
Perturbed gut microbiome development has been linked to childhood malnutrition. Here, we characterize bacterial Toll/interleukin-1 receptor (TIR) protein domains that metabolize nicotinamide adenine dinucleotide (NAD), a co-enzyme with far-reaching effects on human physiology. A consortium of 26 human gut bacterial strains, representing the diversity of TIRs observed in the microbiome and the NAD hydrolase (NADase) activities of a subset of 152 bacterial TIRs assayed in vitro, was introduced into germ-free mice. Integrating mass spectrometry and microbial RNA sequencing (RNA-seq) with consortium membership manipulation disclosed that a variant of cyclic-ADPR (v-cADPR-x) is a specific product of TIR NADase activity and a prominent, colonization-discriminatory, taxon-specific metabolite. Guided by bioinformatic analyses of biochemically validated TIRs, we find that acute malnutrition is associated with decreased fecal levels of genes encoding TIRs known or predicted to generate v-cADPR-x, as well as decreased levels of the metabolite itself. These results underscore the need to consider microbiome TIR NADases when evaluating NAD metabolism in the human holobiont
A new, fast algorithm for detecting protein coevolution using maximum compatible cliques
<p>Abstract</p> <p>Background</p> <p>The MatrixMatchMaker algorithm was recently introduced to detect the similarity between phylogenetic trees and thus the coevolution between proteins. MMM finds the largest common submatrices between pairs of phylogenetic distance matrices, and has numerous advantages over existing methods of coevolution detection. However, these advantages came at the cost of a very long execution time.</p> <p>Results</p> <p>In this paper, we show that the problem of finding the maximum submatrix reduces to a multiple maximum clique subproblem on a graph of protein pairs. This allowed us to develop a new algorithm and program implementation, MMMvII, which achieved more than 600× speedup with comparable accuracy to the original MMM.</p> <p>Conclusions</p> <p>MMMvII will thus allow for more more extensive and intricate analyses of coevolution.</p> <p>Availability</p> <p>An implementation of the MMMvII algorithm is available at: <url>http://www.uhnresearch.ca/labs/tillier/MMMWEBvII/MMMWEBvII.php</url></p
Probing Charge-Symmetry-Violating Quark Distributions in Semi-Inclusive Leptoproduction of Hadrons
Recent experiments by the HERMES group at HERA are measuring semi-inclusive
electroproduction of pions from deuterium. We point out that by comparing the
production of and from an isoscalar target, it is possible, in
principle, to measure charge symmetry violation in the valence quark
distributions of the nucleons. It is also possible in the same experiments to
obtain an independent measurement of the quark fragmentation functions. We
review the information which can be deduced from such experiments and show the
``signature'' for charge symmetry violation in such experiments. Finally, we
predict the magnitude of the charge symmetry violation, from both the valence
quark distributions and the pion fragmentation function, which might be
expected in these experiments.Comment: 19 pages plus 5 figures, used eps
Finding the Cell Center by a Balance of Dynein and Myosin Pulling and Microtubule Pushing: A Computational Study
By comparing computer modeling predictions with observations, we conclude that strong dynein and weaker myosin-generated forces pull the microtubules inward competing with microtubule plus-ends pushing the microtubule aster outward and that the balance of these forces positions the centrosome at the cell center
The COMBREX Project: Design, Methodology, and Initial Results
© 2013 Brian P. et al.Prior to the “genomic era,” when the acquisition of DNA sequence involved significant labor and expense, the sequencing of genes was strongly linked to the experimental characterization of their products. Sequencing at that time directly resulted from the need to understand an experimentally determined phenotype or biochemical activity. Now that DNA sequencing has become orders of magnitude faster and less expensive, focus has shifted to sequencing entire genomes. Since biochemistry and genetics have not, by and large, enjoyed the same improvement of scale, public sequence repositories now predominantly contain putative protein sequences for which there is no direct experimental evidence of function. Computational approaches attempt to leverage evidence associated with the ever-smaller fraction of experimentally analyzed proteins to predict function for these putative proteins. Maximizing our understanding of function over the universe of proteins in toto requires not only robust computational methods of inference but also a judicious allocation of experimental resources, focusing on proteins whose experimental characterization will maximize the number and accuracy of follow-on predictions.COMBREX is funded by a GO grant from the National Institute of General Medical Sciences (NIGMS) (1RC2GM092602-01).Peer Reviewe
Stability, structure and scale: improvements in multi-modal vessel extraction for SEEG trajectory planning
A new, fast algorithm for detecting protein coevolution using maximum compatible cliques
Abstract
Background
The MatrixMatchMaker algorithm was recently introduced to detect the similarity between phylogenetic trees and thus the coevolution between proteins. MMM finds the largest common submatrices between pairs of phylogenetic distance matrices, and has numerous advantages over existing methods of coevolution detection. However, these advantages came at the cost of a very long execution time.
Results
In this paper, we show that the problem of finding the maximum submatrix reduces to a multiple maximum clique subproblem on a graph of protein pairs. This allowed us to develop a new algorithm and program implementation, MMMvII, which achieved more than 600× speedup with comparable accuracy to the original MMM.
Conclusions
MMMvII will thus allow for more more extensive and intricate analyses of coevolution.
Availability
An implementation of the MMMvII algorithm is available at:
http://www.uhnresearch.ca/labs/tillier/MMMWEBvII/MMMWEBvII.ph