Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure

Multi-tissue coexpression networks reveal unexpected subnetworks associated with disease

Tissue-to-tissue coexpression networks between genes in hypothalamus, liver or adipose tissue enable identification of obesity-specific genes

Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'

We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.

‘Sciencenet’—towards a global search and share engine for all scientific knowledge

Summary: Modern biological experiments create vast amounts of data which are geographically distributed. These datasets consist of petabytes of raw data and billions of documents. Yet to the best of our knowledge, a search engine technology that searches and cross-links all different data types in life sciences does not exist

DNA nucleotide-specific modulation of \mu A transverse edge currents through a metallic graphene nanoribbon with a nanopore

We propose two-terminal devices for DNA sequencing which consist of a metallic graphene nanoribbon with zigzag edges (ZGNR) and a nanopore in its interior through which the DNA molecule is translocated. Using the nonequilibrium Green functions combined with density functional theory, we demonstrate that each of the four DNA nucleotides inserted into the nanopore, whose edge carbon atoms are passivated by either hydrogen or nitrogen, will lead to a unique change in the device conductance. Unlike other recent biosensors based on transverse electronic transport through DNA nucleotides, which utilize small (of the order of pA) tunneling current across a nanogap or a nanopore yielding a poor signal-to-noise ratio, our device concept relies on the fact that in ZGNRs local current density is peaked around the edges so that drilling a nanopore away from the edges will not diminish the conductance. Inserting a DNA nucleotide into the nanopore affects the charge density in the surrounding area, thereby modulating edge conduction currents whose magnitude is of the order of \mu A at bias voltage ~ 0.1 V. The proposed biosensor is not limited to ZGNRs and it could be realized with other nanowires supporting transverse edge currents, such as chiral GNRs or wires made of two-dimensional topological insulators.Comment: 6 pages, 6 figures, PDFLaTe

Dosage compensation is less effective in birds than in mammals

<p>Abstract</p> <p>Background</p> <p>In animals with heteromorphic sex chromosomes, dosage compensation of sex-chromosome genes is thought to be critical for species survival. Diverse molecular mechanisms have evolved to effectively balance the expressed dose of X-linked genes between XX and XY animals, and to balance expression of X and autosomal genes. Dosage compensation is not understood in birds, in which females (ZW) and males (ZZ) differ in the number of Z chromosomes.</p> <p>Results</p> <p>Using microarray analysis, we compared the male:female ratio of expression of sets of Z-linked and autosomal genes in two bird species, zebra finch and chicken, and in two mammalian species, mouse and human. Male:female ratios of expression were significantly higher for Z genes than for autosomal genes in several finch and chicken tissues. In contrast, in mouse and human the male:female ratio of expression of X-linked genes is quite similar to that of autosomal genes, indicating effective dosage compensation even in humans, in which a significant percentage of genes escape X-inactivation.</p> <p>Conclusion</p> <p>Birds represent an unprecedented case in which genes on one sex chromosome are expressed on average at constitutively higher levels in one sex compared with the other. Sex-chromosome dosage compensation is surprisingly ineffective in birds, suggesting that some genomes can do without effective sex-specific sex-chromosome dosage compensation mechanisms.</p

Nematic liquid crystal alignment on chemical patterns

Patterned Self-Assembled Monolayers (SAMs) promoting both homeotropic and planar degenerate alignment of 6CB and 9CB in their nematic phase, were created using microcontact printing of functionalised organothiols on gold films. The effects of a range of different pattern geometries and sizes were investigated, including stripes, circles and checkerboards. EvanescentWave Ellipsometry was used to study the orientation of the liquid crystal (LC) on these patterned surfaces during the isotropic-nematic phase transition. Pretransitional growth of a homeotropic layer was observed on 1 ¹m homeotropic aligning stripes, followed by a homeotropic mono-domain state prior to the bulk phase transition. Accompanying Monte-Carlo simulations of LCs aligned on nano-patterned surfaces were also performed. These simulations also showed the presence of the homeotropic mono-domain state prior to the transition.</p

Transverse Electronic Transport through DNA Nucleotides with Functionalized Graphene Electrodes

Graphene nanogaps and nanopores show potential for the purpose of electrical DNA sequencing, in particular because single-base resolution appears to be readily achievable. Here, we evaluated from first principles the advantages of a nanogap setup with functionalized graphene edges. To this end, we employed density functional theory and the non-equilibrium Green's function method to investigate the transverse conductance properties of the four nucleotides occurring in DNA when located between the opposing functionalized graphene electrodes. In particular, we determined the electrical tunneling current variation as a function of the applied bias and the associated differential conductance at a voltage which appears suitable to distinguish between the four nucleotides. Intriguingly, we observe for one of the nucleotides a negative differential resistance effect.Comment: 19 pages, 7 figure

Cis and Trans Effects of Human Genomic Variants on Gene Expression

This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731).