The distance-profile representation and its application to detection of distantly related protein families

BACKGROUND: Detecting homology between remotely related protein families is an important problem in computational biology since the biological properties of uncharacterized proteins can often be inferred from those of homologous proteins. Many existing approaches address this problem by measuring the similarity between proteins through sequence or structural alignment. However, these methods do not exploit collective aspects of the protein space and the computed scores are often noisy and frequently fail to recognize distantly related protein families. RESULTS: We describe an algorithm that improves over the state of the art in homology detection by utilizing global information on the proximity of entities in the protein space. Our method relies on a vectorial representation of proteins and protein families and uses structure-specific association measures between proteins and template structures to form a high-dimensional feature vector for each query protein. These vectors are then processed and transformed to sparse feature vectors that are treated as statistical fingerprints of the query proteins. The new representation induces a new metric between proteins measured by the statistical difference between their corresponding probability distributions. CONCLUSION: Using several performance measures we show that the new tool considerably improves the performance in recognizing distant homologies compared to existing approaches such as PSIBLAST and FUGUE

Cyclosporine A Eye Drop-Induced Elongated Eyelashes: A Case Report

Purpose: The most common ocular adverse event following the use of cyclosporine A (CsA) 0.05% ophthalmic emulsion is ocular burning (17%). Other adverse effects that have been reported include conjunctival hyperemia (1–5%), discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging and blurred vision. Here, we report a specific side effect of CsA, namely eye drop-induced eyelash elongation in a patient with refractory giant papillary conjunctivitis. Design: Observational case report. Methods: Case report and review of the literature. Results: A 32-year-old female with giant papillary conjunctivitis on the left eye, who had undergone papillectomy 3 years previously and was refractory to topical steroid therapy, was treated with CsA 0.05% ophthalmic emulsion (Restasis) 4 times a day, preservative-free artificial tears and gentamicin ophthalmic solution in the left eye. After 5 months of topical CsA treatment, elongated eyelashes of her left eye were observed without other adverse effects. Conclusion: Although hypertrichosis and trichomegaly have been documented in the literature as side effects of systemic CsA, topical CsA 0.05% eye drop-induced elongated eyelashes have not been reported, and we believe ophthalmologists should be mindful and inform patients about this specific side effect

Patterns of basal signaling heterogeneity can distinguish cellular populations with different drug sensitivities

Non small cell lung cancer H460 clones exhibit a high degree of heterogeneity in signaling states.Clones with similar patterns of basal signaling heterogeneity have similar paclitaxel sensitivities.Models of signaling heterogeneity among the clones can be used to classify sensitivity to paclitaxel for other cancer populations

Major Cellular and Physiological Impacts of Ocean Acidification on a Reef Building Coral

As atmospheric levels of CO2 increase, reef-building corals are under greater stress from both increased sea surface temperatures and declining sea water pH. To date, most studies have focused on either coral bleaching due to warming oceans or declining calcification due to decreasing oceanic carbonate ion concentrations. Here, through the use of physiology measurements and cDNA microarrays, we show that changes in pH and ocean chemistry consistent with two scenarios put forward by the Intergovernmental Panel on Climate Change (IPCC) drive major changes in gene expression, respiration, photosynthesis and symbiosis of the coral, Acropora millepora, before affects on biomineralisation are apparent at the phenotype level. Under high CO2 conditions corals at the phenotype level lost over half their Symbiodinium populations, and had a decrease in both photosynthesis and respiration. Changes in gene expression were consistent with metabolic suppression, an increase in oxidative stress, apoptosis and symbiont loss. Other expression patterns demonstrate upregulation of membrane transporters, as well as the regulation of genes involved in membrane cytoskeletal interactions and cytoskeletal remodeling. These widespread changes in gene expression emphasize the need to expand future studies of ocean acidification to include a wider spectrum of cellular processes, many of which may occur before impacts on calcification

The Canonical Representation of Proteins: Application to Remote Homology Recognition

Homology establishes the evolutionary relationship among different organisms, and the biological properties of uncharacterized proteins can often be inferred from those of homologous proteins. Our ability to detect subtle similarities between proteins depends strongly on the representations we employ for proteins. Sequence and structure are two possible representation

TWO-PHASE NONPARAMETRIC ICA ALGORITHM FOR BLIND SEPARATION OF INSTANTANEOUS LINEAR MIXTURES

We propose a nonparametric independent component analysis (ICA) algorithm for the problem of blind source separation with instantaneous, time-invariant and linear mixtures. Our Init-NLE algorithm combines minimization of correlation among nonlinear expansions of the output signals with a good initialization derived from search guided by statistical tests for independence based on the power-divergent family of test statistics. Such initialization is critical to reliable separation. The simulation results obtained from both synthetic and real-life data show that our method yields consistent results and compares favorably to the existing ICA algorithms. 1

Network crosstalk dynamically changes during neutrophil polarization.

How complex signaling networks shape highly coordinated, multistep cellular responses is poorly understood. Here, we made use of a network-perturbation approach to investigate causal influences, or "crosstalk," among signaling modules involved in the cytoskeletal response of neutrophils to chemoattractant. We quantified the intensity and polarity of cytoskeletal marker proteins over time to characterize stereotyped cellular responses. Analyzing the effects of network disruptions revealed that, not only does crosstalk evolve rapidly during polarization, but also that intensity and polarity responses are influenced by different patterns of crosstalk. Interestingly, persistent crosstalk is arranged in a surprisingly simple circuit: a linear cascade from front to back to microtubules influences intensities, and a feed-forward network in the reverse direction influences polarity. Our approach provided a rational strategy for decomposing a complex, dynamically evolving signaling system and revealed evolving paths of causal influence that shape the neutrophil polarization response