BioIE: extracting informative sentences from the biomedical literature

SUMMARY: BioIE is a rule-based system that extracts informative sentences relating to protein families, their structures, functions and diseases from the biomedical literaturE. Based on manual definition of templates and rules, it aims at precise sentence extraction rather than wide recall. After uploading source text or retrieving abstracts from MEDLINE, users can extract sentences based on predefined or user-defined template categories. BioIE also provides a brief insight into the syntactic and semantic context of the source-text by looking at word, N-gram and MeSH-term distributions. Important Applications of BioIE are in, for example, annotation of microarray data and of protein databases. AVAILABILITY: http://umber.sbs.man.ac.uk/dbbrowser/bioie/     

A quantitative model for linking two disparate sets of articles in MEDLINE

BACKGROUND: Identifying information that implicitly links two disparate sets of articles is a fundamental and intuitive data mining strategy that can help investigators address real scientific questions. The Arrowsmith two-node search finds title words and phrases (so-called B-terms) that are shared across two sets of articles within MEDLINE and displays them in a manner that facilitates human assessment. A serious stumbling-block has been the lack of a quantitative model for predicting which of the hundreds if not thousands of B-terms computed for a given search are most likely to be relevant to the investigator. METHODOLOGY/PRINCIPAL FINDINGS: Using a public two-node search interface, field testers devised a set of two-node searches under real life conditions and a certain number of B-terms were marked relevant. These were employed as 'gold standards;' each B-term was characterized according to eight complementary features that were strongly correlated with relevance. A logistic regression model was developed that permits one to estimate the probability of relevance for each B-term, to rank B-terms according to their likely relevance, and to estimate the overall number of relevant B-terms inherent in a given two-node search. CONCLUSIONS/SIGNIFICANCE: The model greatly simplifies and streamlines the process of carrying out a two-node search, and may be applicable to a number of other literature-based discovery applications, including the so-called one-node search and related gene-centric strategies that incorporate implicit links to predict how genes may be related to each other and to human diseases. This should encourage much wider exploration of text mining for implicit information among the general scientific community. AVAILABILITY: Two-node searches can be carried out freely at http://arrowsmith.psych.uic.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.     

Improved recognition of figures containing fluorescence microscope images in online journal articles using graphical models

MOTIVATION: There is extensive interest in automating the collection, organization and analysis of biological data. Data in the form of images in online literature present special challenges for such efforts. The first steps in understanding the contents of a figure are decomposing it into panels and determining the type of each panel. In biological literature, panel types include many kinds of images collected by different techniques, such as photographs of gels or images from microscopes. We have previously described the SLIF system (http://slif.cbi.cmu.edu) that identifies panels containing fluorescence microscope images among figures in online journal articles as a prelude to further analysis of the subcellular patterns in such images. This system contains a pretrained classifier that uses image features to assign a type (class) to each separate panel. However, the types of panels in a figure are often correlated, so that we can consider the class of a panel to be dependent not only on its own features but also on the types of the other panels in a figure. RESULTS: In this article, we introduce the use of a type of probabilistic graphical model, a factor graph, to represent the structured information about the images in a figure, and permit more robust and accurate inference about their types. We obtain significant improvement over results for considering panels separately. AVAILABILITY: The code and data used for the experiments described here are available from http://murphylab.web.cmu.edu/software.     

Working memory: linking capacity with selectivity

Working memory is one of the most intensively studied psychological processes, but little is known about what distinguishes individuals in their working memory capacity. Recent evidence from electroencephalogram recordings suggests that one crucial component of this variation is our ability to exclude irrelevant information.     

Rho proteins: linking signaling with membrane trafficking

Rho proteins are well known for their effects on the actin cytoskeleton, and are activated in response to a variety of extracellular stimuli. Several Rho family members are localized to vesicular compartments, and increasing evidence suggests that they play important roles in the trafficking of vesicles on both endocytic and exocytic pathways. In particular, RhoA, RhoB, RhoD, Rac and Cdc42 have been shown to affect various steps of membrane trafficking. The underlying molecular basis for these effects of Rho proteins are incompletely understood, but in the case of Cdc42 it appears that it can drive vesicle movement through Arp2/3 complex-mediated actin polymerization at the surface of the vesicle. This is similar to what is believed to happen when Rac and Cdc42 stimulate actin polymerization at the plasma membrane. Rho proteins may also affect membrane trafficking by altering phosphatidylinositide composition of membrane compartments, or through interactions with microtubules.     

To SIR with Polycomb: linking silencing mechanisms

Yeast SIR2, the most evolutionarily conserved deacetylase, plays an essential role in epigenetic silencing at the silent mating type loci and telomeres. SIR2 has been implicated in chromatin silencing and lifespan determination in several organisms. Discovery that Drosophila SIR2 is also involved in epigenetic silencing mediated by the Polycomb group proteins and is physically associated with a complex containing the E(Z) histone methyltransferase has wide implications. These findings suggest possible link of Polycomb system to diverse cellular processes including senescence.     

Binocular coordination: reading stereoscopic sentences in depth

The present study employs a stereoscopic manipulation to present sentences in three dimensions to subjects as they read for comprehension. Subjects read sentences with (a) no depth cues, (b) a monocular depth cue that implied the sentence loomed out of the screen (i.e., increasing retinal size), (c) congruent monocular and binocular (retinal disparity) depth cues (i.e., both implied the sentence loomed out of the screen) and (d) incongruent monocular and binocular depth cues (i.e., the monocular cue implied the sentence loomed out of the screen and the binocular cue implied it receded behind the screen). Reading efficiency was mostly unaffected, suggesting that reading in three dimensions is similar to reading in two dimensions. Importantly, fixation disparity was driven by retinal disparity; fixations were significantly more crossed as readers progressed through the sentence in the congruent condition and significantly more uncrossed in the incongruent condition. We conclude that disparity depth cues are used on-line to drive binocular coordination during reading.     

Phenotypic plasticity: linking molecular mechanisms with evolutionary outcomes

We argue that phenotypic plasticity should be broadly construed to encompass a diversity of phenomena spanning several hierarchical levels of organization. Despite seemingly disparate outcomes among different groups of organisms (e.g., the opening/closing of stomata in leaves, adjustments of allocation to growth/reproduction, or the production of different castes in social insects), there are underlying shared processes that initiate these responses. At the most fundamental level, all plastic responses originate at the level of individual cells, which receive and process signals from their environment. The broad variations in physiology, morphology, behavior, etc., that can be produced by a single genotype, can be accounted for by processes regulating gene expression in response to environmental variation. Although evolution of adaptive plasticity may not be possible for some types of environmental signals, in many cases selection has molded responses to environmental variation that generate precise and repeatable patterns of gene expression. We highlight the example of responses of plants to variation in light quality and quantity, mediated via the phytochrome genes. Responses to changes in light at particular stages of plants' life cycles (e.g., seed germination, competition, reproduction) are controlled by different members of this gene family. The mechanistic details of the cell and molecular biology of phytochrome gene action (e.g., their effects on expression of other genes) is outlined. Plasticity of cells and organisms to internal and external environmental signals is pervasive, and represents not just an outcome of evolutionary processes, but also a potentially important molder of them. Phenotypes originally initiated via a plastic response, can be fixed through genetic assimilation as alternate regulatory pathways are shut off. Evolution of mechanisms of plasticity and canalization can both reduce genetic variation, as well as shield it. When the organism encounters novel environmental conditions, this shielded variation may be expressed, revealing hidden reaction norms that represent the raw material for subsequent evolution.     

Chaos in abstract kinetics: Two prototypes

“Spiral-type chaos” and “screw-type chaos” constitute two simple types of nonperiodic oscillatory flow in 3-variable continuous systems. The former type is exhibited, for example, by auniversal system in the switching mode, when the regimens of flow on the two stable branches of the slow manifold in state space are made to differ in an appropriate manner. Screw-type chaos occurs in ahysteresis oscillator between two stable limit cycles, if the rotation gain is positive. For either case, an analogous 2-dimensional “branched papersheet flow” exists. Both flows are determined by a single-variable discrete dynamical system of the Lorenz-Li-Yorke type (as a cross-section), as well as by an equivalent new map. Numerical simulations of two abstract reaction systems giving rise to non-idealized (that is, truly 3-dimensional) flows of either type are presented. The corresponding discrete dynamical systems (Poincaré maps) are 2-dimensional now, having the form of a flattened hairpin (“horseshoe”) in the simplest case. Thus, two actual examples for 3-dimensional flows suspended by a horseshoe diffeomorphism seem to have been found. One contains just a single functionally effective nonlinearity. Real systems of either type may be found in physics, chemistry, biochemistry, biophysics and economy.     

Leptin: linking adipocyte metabolism with cardiovascular and autoimmune diseases

Leptin was originally discovered as an adipocyte-derived hormone involved in the central control of body weight and energy homeostasis. It is now clear that leptin is a pleiotropic cytokine, with activities on many peripheral cell types. These findings may help explain the surprising role of leptin in pathophysiological processes. Recent evidence suggests that leptin contributes to atherosclerosis and to the increased risk of cardiovascular disease in obese people. Leptin also appears to be involved in T-cell-dependent immunity and possibly in the development and maintenance of certain autoimmune diseases. Here, we review the role of leptin in cardiovascular and autoimmune diseases, and also briefly address the potential therapeutic use of leptin antagonists.