Temporal patterns of gene expression via nonmetric multidimensional scaling analysis

Motivation: Microarray experiments result in large scale data sets that require extensive mining and refining to extract useful information. We have been developing an efficient novel algorithm for nonmetric multidimensional scaling (nMDS) analysis for very large data sets as a maximally unsupervised data mining device. We wish to demonstrate its usefulness in the context of bioinformatics. In our motivation is also an aim to demonstrate that intrinsically nonlinear methods are generally advantageous in data mining. Results: The Pearson correlation distance measure is used to indicate the dissimilarity of the gene activities in transcriptional response of cell cycle-synchronized human fibroblasts to serum [Iyer et al., Science vol. 283, p83 (1999)]. These dissimilarity data have been analyzed with our nMDS algorithm to produce an almost circular arrangement of the genes. The temporal expression patterns of the genes rotate along this circular arrangement. If an appropriate preparation procedure may be applied to the original data set, linear methods such as the principal component analysis (PCA) could achieve reasonable results, but without data preprocessing linear methods such as PCA cannot achieve a useful picture. Furthermore, even with an appropriate data preprocessing, the outcomes of linear procedures are not as clearcut as those by nMDS without preprocessing.Comment: 11 pages, 6 figures + online only 2 color figures, submitted to Bioinformatic

Synthesis, characterization and performance of polystyrene/PMMA blend membranes for potential water treatment

© 2017 Elsevier B.V. PS membranes were prepared from polymeric blends of PS and PMMA via a phase inversion induced by an immersion precipitation in water coagulation baths. The effects of the casting parameters (e.g., solvent selection, the composition of the coagulation bath) and the type of polystyrene (substituents at the aromatic ring, tacticity) on the morphology and water permeation flux were studied. The findings reveal that modified PS promoting instantaneous demixing with NMP/water systems result in membranes wit- h macrovoids while the addition of 2% of PS-r-PMMA results in membranes with high water fluxes. The membranes morphologies were governed by a trade-off between thermodynamic and kinetic aspects. The antibacterial effect of (aPS)70-co-aPS(I)30/PMMA-based membrane was examined using static and cross-flow systems. These results illustrate the diversity in the design of these PS/PMMA based membranes and highlight the possibility to control the polymer chemistry for tailoring specific morphology, permeation, and antibacterial properties for the desired function

Energetic and Environmental Constraints on the Community Structure of Benthic Microbial Mats in Lake Fryxell, Antarctica.

Ecological communities are regulated by the flow of energy through environments. Energy flow is typically limited by access to photosynthetically active radiation (PAR) and oxygen concentration (O2). The microbial mats growing on the bottom of Lake Fryxell, Antarctica, have well-defined environmental gradients in PAR and (O2). We analyzed the metagenomes of layers from these microbial mats to test the extent to which access to oxygen and light controls community structure. We found variation in the diversity and relative abundances of Archaea, Bacteria and Eukaryotes across three (O2) and PAR conditions: high (O2) and maximum PAR, variable (O2) with lower maximum PAR, and low (O2) and maximum PAR. We found distinct communities structured by the optimization of energy use on a millimeter-scale across these conditions. In mat layers where (O2) was saturated, PAR structured the community. In contrast, (O2) positively correlated with diversity and affected the distribution of dominant populations across the three habitats, suggesting that meter-scale diversity is structured by energy availability. Microbial communities changed across covarying gradients of PAR and (O2). The comprehensive metagenomic analysis suggests that the benthic microbial communities in Lake Fryxell are structured by energy flow across both meter- and millimeter-scales

Determining Physical Constraints in Transcriptional Initiation Complexes Using DNA Sequence Analysis

Eukaryotic gene expression is often under the control of cooperatively acting transcription factors whose binding is limited by structural constraints. By determining these structural constraints, we can understand the “rules” that define functional cooperativity. Conversely, by understanding the rules of binding, we can infer structural characteristics. We have developed an information theory based method for approximating the physical limitations of cooperative interactions by comparing sequence analysis to microarray expression data. When applied to the coordinated binding of the sulfur amino acid regulatory protein Met4 by Cbf1 and Met31, we were able to create a combinatorial model that can correctly identify Met4 regulated genes. Interestingly, we found that the major determinant of Met4 regulation was the sum of the strength of the Cbf1 and Met31 binding sites and that the energetic costs associated with spacing appeared to be minimal

Position specific variation in the rate of evolution in transcription factor binding sites

BACKGROUND: The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. RESULTS: Here we analyse the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikatae to study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artefacts of computational motif finding algorithms. CONCLUSION: As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the effective use of comparative sequence data in the identification of transcription factor binding sites and is an important step toward understanding the evolution of functional non-coding DNA

PathCluster: a framework for gene set-based hierarchical clustering

Motivation: Gene clustering and gene set-based functional analysis are widely used for the analysis of expression profiles. The development of a comprehensive method jointly combining the two methods would allow for greater biological insights

Evaluation of the /sup 63/Cu activation foil for determining the neutron dose in the energy range of 1 eV to 1 MeV

The appropriateness of the /sup 63/Cu activation foil for determining the neutron dose in the energy region from 1 eV to 1 MeV has been investigated for spectra of seven different criticality accident configurations. A program was written for folding the published spectra with the /sup 63/Cu activation cross sections and with the fluence-to-dose or kerma conversion factors. It is shown that for these spectra the neutron dose and kerma result primarily from the energy region above 15 keV whereas the measured /sup 64/Cu activity is mainly determined by the fluence in the region between 1 eV and 15 keV. Uncertainties in the fluence spectrum in the low-energy region between 1 eV and 15 keV, which in reality do not affect the dose contribution, might lead to large deviations in the measured /sup 64/Cu activity and hence to the derived dose in the 1 eV to 1 MeV range. Use of /sup 10/B shielding for attenuating the fluence in the 1-eV to 15-keV region was evaluated, leading to the conclusion that the necessary amount of boron material is unacceptably large and would appreciably increase the cost of the dosimeter currently used at Los Alamos. The lower limit of neutron detectability would also be increased

MONKEY: identifying conserved transcription-factor binding sites in multiple alignments using a binding site-specific evolutionary model

We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding-site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function

Flexible Promoter Architecture Requirements for Coactivator Recruitment

Background: The spatial organization of transcription factor binding sites in regulatory DNA, and the composition of intersite sequences, influences the assembly of the multiprotein complexes that regulate RNA polymerase recruitment and thereby affects transcription. We have developed a genetic approach to investigate how reporter gene transcription is affected by varying the spacing between transcription factor binding sites. We characterized the components of promoter architecture that govern the yeast transcription factors Cbf1 and Met31/32, which bind independently, but collaboratively recruit the coactivator Met4. Results: A Cbf1 binding site was required upstream of a Met31/32 binding site for full reporter gene expression. Distance constraints on coactivator recruitment were more flexible than those for cooperatively binding transcription factors. Distances from 18 to 50 bp between binding sites support efficient recruitment of Met4, with only slight modulation by helical phasing. Intriguingly, we found that certain sequences located between the binding sites abolished gene expression. Conclusion: These results yield insight to the influence of both binding site architecture and local DNA flexibility on gene expression, and can be used to refine computational predictions of gene expression from promoter sequences. In addition, our approach can be applied to survey promoter architecture requirements for arbitrary combinations of transcription factor binding sites