TFM-Explorer: mining cis-regulatory regions in genomes

DNA-binding transcription factors (TFs) play a central role in transcription regulation, and computational approaches that help in elucidating complex mechanisms governing this basic biological process are of great use. In this perspective, we present the TFM-Explorer web server that is a toolbox to identify putative TF binding sites within a set of upstream regulatory sequences of genes sharing some regulatory mechanisms. TFM-Explorer finds local regions showing overrepresentation of binding sites. Accepted organisms are human, mouse, rat, chicken and drosophila. The server employs a number of features to help users to analyze their data: visualization of selected binding sites on genomic sequences, and selection of cis-regulatory modules. TFM-Explorer is available at http://bioinfo.lifl.fr/TFM

Geomechanical Response Of Overburden Caused By CO2 Injection Into A Depleted Oil Reservoir

This study investigates the hydro-mechanical aspects of carbon dioxide (CO2) injection into a depleted oil reservoir through the use of coupled multiphase fluid flow and geomechanical modeling. Both single-phase and multiphase fluid flow analyses coupled with geomechanics were carried out at the West Pearl Queen depleted oil reservoir site, and modeling results were compared with available measured data. The site geology and the material properties determined on the basis of available geophysical data were used in the analyses. Modeling results from the coupled multiphase fluid flow and geomechanical analyses show that computed fluid pressures match well with available measured data. The hydro-mechanical properties of the reservoir have a significant influence on computed fluid pressures and surface deformations. Hence, an accurate geologic characterization of the sequestration site and determination of engineering properties are important issues for the reliability of model predictions. The computed fluid pressure response is also significantly influenced by the relative permeability curves used in multiphase fluid flow models. While the multiphase fluid flow models provide more accurate fluid pressure response, single-phase fluid flow models can be used to obtain approximate solutions. The ground surface deformations obtained from single-phase fluid flow models coupled with geomechanics are slightly lower than those predicted by multiphase fluid flow models coupled with geomechanics. However, the advantage of a single-phase model is the simplicity. Limited field monitoring of subsurface fluid pressure and ground surface deformations during fluid injection can be used in calibrating coupled fluid flow and geomechanical models. The calibrated models can be used for investigating the performance of large-scale CO2 storage in depleted oil reservoirs

Sequence alignment, mutual information, and dissimilarity measures for constructing phylogenies

Existing sequence alignment algorithms use heuristic scoring schemes which cannot be used as objective distance metrics. Therefore one relies on measures like the p- or log-det distances, or makes explicit, and often simplistic, assumptions about sequence evolution. Information theory provides an alternative, in the form of mutual information (MI) which is, in principle, an objective and model independent similarity measure. MI can be estimated by concatenating and zipping sequences, yielding thereby the "normalized compression distance". So far this has produced promising results, but with uncontrolled errors. We describe a simple approach to get robust estimates of MI from global pairwise alignments. Using standard alignment algorithms, this gives for animal mitochondrial DNA estimates that are strikingly close to estimates obtained from the alignment free methods mentioned above. Our main result uses algorithmic (Kolmogorov) information theory, but we show that similar results can also be obtained from Shannon theory. Due to the fact that it is not additive, normalized compression distance is not an optimal metric for phylogenetics, but we propose a simple modification that overcomes the issue of additivity. We test several versions of our MI based distance measures on a large number of randomly chosen quartets and demonstrate that they all perform better than traditional measures like the Kimura or log-det (resp. paralinear) distances. Even a simplified version based on single letter Shannon entropies, which can be easily incorporated in existing software packages, gave superior results throughout the entire animal kingdom. But we see the main virtue of our approach in a more general way. For example, it can also help to judge the relative merits of different alignment algorithms, by estimating the significance of specific alignments.Comment: 19 pages + 16 pages of supplementary materia

Efficient Screening of CRISPR/Cas9-Induced Events in Drosophila Using a Co-CRISPR Strategy

Genome editing using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and associated nuclease (Cas9) enables specific genetic modifications, including deletions, insertions, and substitutions in numerous organisms, such as the fruit fly Drosophila melanogaster. One challenge of the CRISPR/Cas9 system can be the laborious and time-consuming screening required to find CRISPR-induced modifications due to a lack of an obvious phenotype and low frequency after editing. Here we apply the successful co-CRISPR technique in Drosophila to simultaneously target a gene of interest and a marker gene, ebony, which is a recessive gene that produces dark body color and has the further advantage of not being a commonly used transgenic marker. We found that Drosophila broods containing higher numbers of CRISPR-induced ebony mutations (“jackpot” lines) are significantly enriched for indel events in a separate gene of interest, while broods with few or no ebony offspring showed few mutations in the gene of interest. Using two different PAM sites in our gene of interest, we report that ∼61% (52–70%) of flies from the ebony-enriched broods had an indel in DNA near either PAM site. Furthermore, this marker mutation system may be useful in detecting the less frequent homology-directed repair events, all of which occurred in the ebony-enriched broods. By focusing on the broods with a significant number of ebony flies, successful identification of CRISPR-induced events is much faster and more efficient. The co-CRISPR technique we present significantly improves the screening efficiency in identification of genome-editing events in Drosophila

Conversations between carers and people with schizophrenia: A qualitative analysis using leximancer

We examined conversations between people with schizophrenia (PwS) and family or professional carers with whom they interacted frequently. We allocated PwS to one of two communication profiles: Low-activity communicators talked much less than their conversational partners, whereas high-activity communicators talked much more. We used Leximancer text analytics software to analyze the conversations. We found that carers used different strategies to accommodate to the PwS's behavior, depending on the PwS's communication profile and their relationship. These findings indicate that optimal communication strategies depend on the PwS's conversational tendencies and the relationship context. They also suggest new opportunities for qualitative assessment via intelligent text analytics technologies. © 2010 The Author(s)