Biological networks and epistasis in genome-wide association studies

Over the last few years, technological improvements have made possible the genotyping of hundreds of thousands of SNPs, enabling whole-genome association studies. The first genome-wide association studies have recently been completed to detect causal variant for complex traits. Although increasing evidence suggests that interaction between loci, such as epistasis between two loci, should be considered, most of these studies proceed by considering each SNP independently. One reason for this choice is that looking at all pairs of SNPs increases dramatically the number of tests (approximatively 50 billions of tests for a 300,000 SNPs data set) that faces with computational limitation and strong multiple testing correction.
We proposed to reduce the number of tests by focusing on pairs of SNPs that belong to genes known to interact in some metabolic network. Although some interactions might be missed, these pairs of genes are good candidates for epistasis. Furthermore the use of protein interaction databases (such as the STRING database) may reduce the number of tests by a factor of 5,000.
Results using this approach will be presented on simulated data sets and on public data sets.
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The citizen lobby: from capacity to influence

The Internet holds endless opportunities for exchange and dialogue and the promise of developing a better democratic model. Day-to-day politics are largely driven by economic lobbies in the interest of what Habermas calls their "generalised particularism," the threat to take jobs and tax revenues elsewhere. Citizens' influence over politicians is twofold: they are asked for their input in elections, referenda, online consultations and surveys, and citizens can initiate issues where they see political action needed. Yet these "participative forces," including NGOs, street rallies and charities, regularly fail to reach the ears of elected politicians as effectively as those of well-funded corporate lobbies. Also, this type of voluntary engagement often falls short of presenting the kind of reasoned challenges to the incumbents - by the electorate - that Habermas' communicative action aimed at. A more powerful model would therefore organise the efforts of the electorate in a way that both generates those reasoned arguments, which, as Habermas quite correctly pointed out differ from mere opinions, and delivers them to the elected politicians in a manner they can neither refuse nor ignore. This is what the Citizen Lobby intends to do

Citizen Lobby

The Internet holds endless opportunities for exchange and dialogue and the promise of developing a better democratic model. Day-to-day politics are largely driven by economic lobbies in the interest of what Habermas calls their „generalised particularism,“ the threat to take jobs and tax revenues elsewhere. Citizens’ influence over politicians is twofold: they are asked for their input in elections, referenda, online consultations and surveys, and citizens can initiate issues where they see political action needed. Yet these “participative forces,” including NGOs, street rallies and charities, regularly fail to reach the ears of elected politicians as effectively as those of well-funded corporate lobbies. Also, this type of voluntary engagement often falls short of presenting the kind of reasoned challenges to the incumbents—by the electorate—that Habermas’ communicative action aimed at. A more powerful model would therefore organise the efforts of the electorate in a way that both generates those reasoned arguments, which, as Habermas quite correctly pointed out differ from mere opinions, and delivers them to the elected politicians in a manner they can neither refuse nor ignore. This is what the Citizen Lobby intends to do

Transmission-mode imaging in the environmental scanning electron microscope (ESEM)

Electron microscopy was first conducted in the 1930s with the advent of the TEM and later the STEM. In 1969, the first commercial SEM was released, with the possibility of retrofitting it to behave like a STEM following soon afterwards. In 1979, Danilatos and Robinson advanced electron microscopy by creating a new type of SEM which allowed a controlled quantity of gas into the sample chamber, termed ESEM. The most recent evolution in this line was the combination of ESEM and STEM in 2005, a procedure termed Wet STEM. The focus of this work is on investigating applications of this new technique, along with the contrast mechanisms involved in forming an image. To that end, a wide variety of samples will be imaged. Clay and paint suspensions (colloids) are used to test Wet STEM’s capacity to image submerged objects, as well as thin objects which are stacked together. Diblock copolymer films are used to test Wet STEM’s ability to distinguish chemically similar materials without staining, the physical effects of heavy metal staining and to demonstrate the necessity of gas for the purpose of charge neutralisation. Single cell biological samples are also investigated. Internal contrast in mammalian cells is visible without recourse to staining, but chemical fixation is required despite maintaining a high relative humidity. Bacteria are more resilient and as such are easier to image than animal cells, requiring no prior treatment. When exposed to low relative humidity, bacteria are found to collapse. The collapse pattern is observed to differ between wild-type and cytoskeletal-deficient bacteria of the same species and strain, so it is likely that dehydration-induced collapse offers information about the position and shape of the bacterial cytoskeleton.This work was funded by the EPSRC [grant number EP/P50385X/1] and by a CASE studentship from FEI Company

Downfront winds over buoyant coastal plumes

Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 3139-3154, doi:10.1175/JPO-D-16-0042.1.Downfront, or downwelling favorable, winds are commonly found over buoyant coastal plumes. It is known that these winds can result in mixing of the plume with the ambient water and that the winds influence the transport, spatial extent, and stability of the plumes. In the present study, the interaction of the Ekman velocity in the surface layer and baroclinic instability supported by the strong horizontal density gradient of the plume is explored with the objective of understanding the potential vorticity and buoyancy budgets. The approach makes use of an idealized numerical model and scaling theory. It is shown that when winds are present the weak stratification resulting from vertical mixing and the strong baroclinicity of the front results in near-zero average potential vorticity q. For weak to moderate winds, the reduction of q by diapycnal mixing is balanced by the generation of q through the geostrophic stress term in the regions of strong horizontal density gradients and stable stratification. However, for very strong winds the wind stress overwhelms the geostrophic stress and leads to a reduction in q, which is balanced by the vertical mixing term. In the absence of winds, the geostrophic stress dominates mixing and the flow rapidly restratifies. Nonlinearity, extremes of relative vorticity and vertical velocity, and mixing are all enhanced by the presence of a coast. Scaling estimates developed for the eddy buoyancy flux, the surface potential vorticity flux, and the diapycnal mixing rate compare well with results diagnosed from a series of numerical model calculations.This study was supported by NSF Grants OCE-1433170 (MAS) and OCE-1459677 (LNT).2017-04-0

Asymmetries in vertical vorticity and vertical velocity arising during nonlinear homogeneous spindown

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of American Institute of Physics for personal use, not for redistribution. The definitive version was published in Physics of Fluids 24 (2012): 076601, doi:10.1063/1.4731280.During the spindown of a uni-directional, geostrophic current in a homogeneous fluid, asymmetry arises in the vertical velocity and vertical relative vorticity fields. A closed-form, time-dependent solution valid to order Rossby number is derived to explore these asymmetries. Momentum advection in the interior and the Ekman layer leads to competing tendencies in the vertical vorticity’s evolution. In the interior, momentum advection hastens spindown in cyclonic regions. In the Ekman layer, momentum advection weakens Ekman pumping over Ekman suction and thus tends to slow the spindown of cyclonic vorticity. It is shown that the former effect dominates, and hence cyclonic vorticity decays faster than anticyclonic vorticity

Enzyme production by filamentous fungi: analysis of the secretome of Trichoderma reesei grown on unconventional carbon source

<p>Abstract</p> <p>Background</p> <p>Spent hydrolysates from bioethanolic fermentation processes based on agricultural residues have potential as an abundant and inexpensive source of pentose sugars and acids that could serve as nutrients for industrial enzyme-producing microorganisms, especially filamentous fungi. However, the enzyme mixtures produced in such media are poorly defined. In this study, the secretome of <it>Trichoderma reesei </it>Rut C-30 grown either on a spent hydrolysate model medium (SHMM) or on a lactose-based standard medium (LBSM) was explored using proteomics.</p> <p>Results</p> <p>Our results show that both the SHMM and LBSM serve as excellent growth media for <it>T. reesei </it>Rut C-30. In total, 52 protein spots on 2-D gels were identified by using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and electrospray ionization liquid chromatography tandem mass spectrometry (ESI-LC MS/MS). As expected, a considerable number of the identified proteins were related to the degradation of lignocellulosic biomass. The enzyme production profiles in the two media were similar, but β-glucosidase and β-galactosidase were only produced in LBSM. The main cellobiohydrolases (Cel7A/Cel6A) and endoglucanases (Cel7B/Cel5A) were identified in both media and the cellobiohydrolases, i.e. Cel7A and Cel6A, were the most abundant cellulolytic enzymes. Moreover, both media can also serve as a potent inducer of xylanolytic enzymes. Several key enzymes involved in sugar assimilation and regulation of cellulase formation were identified, and were found to be differentially expressed in the two growth media.</p> <p>Conclusions</p> <p>This study not only provides a catalogue of the prevalent proteins secreted by <it>T. reesei </it>in the two media, but the results also suggest that production of hydrolytic enzymes using unconventional carbon sources, such as components in spent hydrolysates, deserves further attention in the future.</p