OmicsViz: Cytoscape plug-in for visualizing omics data across species

MOTIVATION: OmicsViz is a Cytoscape plug-in for mapping and visualizing large-scale omics datasets across species, including those with many-to-many mappings between homologs. This allows users to map their data onto pathways of related model organisms. Mapping schemas across species or different experimental protocols allow users to comparatively analyze the omics data. The data can also be visualized in parallel-coordinate plots. AVAILABILITY: The latest version of OmicsViz with documentation, tutorial and jar files can be downloaded from http://metnet.vrac.iastate.edu/MetNet_fcmodeler.htm     

The functional logic of cortico-pulvinar connections

The pulvinar is an 'associative' thalamic nucleus, meaning that most of its input and output relationships are formed with the cerebral cortex. The function of this circuitry is little understood and its anatomy, though much investigated, is notably recondite. This is because pulvinar connection patterns disrespect the architectural subunits (anterior, medial, lateral and inferior pulvinar nuclei) that have been the traditional reference system. This article presents a simplified, global model of the organization of cortico-pulvinar connections so as to pursue their structure-function relationships. Connections between the cortex and pulvinar are topographically organized, and as a result the pulvinar contains a 'map' of the cortical sheet. However, the topography is very blurred. Hence the pulvinar connection zones of nearby cortical areas overlap, allowing indirect transcortical communication via the pulvinar. A general observation is that indirect cortico-pulvino-cortical circuits tend to mimic direct cortico-cortical pathways: this is termed 'the replication principle'. It is equally apt for certain pairs (or groups) of nearby cortical areas that happen not to connect with each other. The 'replication' of this non-connection is achieved by discontinuities and dislocations of the cortical topography within the pulvinar, such that the associated pair of connection zones do not overlap. Certain of these deformations can be used to divide the global cortical topography into specific sub-domains, which form the natural units of a connectional subdivision of the pulvinar. A substantial part of the pulvinar also expresses visual topography, reflecting visual maps in occipital cortex. There are just two well-ordered visual maps in the pulvinar, that both receive projections from area V1, and several other occipital areas; the resulting duplication of cortical topography means that each visual map also acts as a separate connection domain. In summary, the model identifies four topographically ordered connection domains, and reconciles the coexistence of visual and cortical maps in two of them. The replication principle operates at and below the level of domain structure. It is argued that cortico-pulvinar circuitry replicates the pattern of cortical circuitry but not its function, playing a more regulatory role instead. Thalamic neurons differ from cortical neurons in their inherent rhythmicity, and the pattern of cortico-thalamic connections must govern the formation of specific resonant circuits. The broad implication is that the pulvinar acts to coordinate cortical information processing by facilitating and sustaining the formation of synchronized trans-areal assemblies; a more pointed suggestion is that, owing to the considerable blurring of cortical topography in the pulvinar, rival cortical assemblies may be in competition to recruit thalamic elements in order to outlast each other in activity.     

ET viewer: an application for predicting and visualizing functional sites in protein structures

SUMMARY: The Evolutionary Trace Viewer (ETV) provides a one-stop environment in which to run, visualize and interpret Evolutionary Trace (ET) predictions of functional sites in protein structures. ETV is implemented using Java to run across different operating systems using Java Web Start technology. AVAILABILITY: The ETV is available for download from our website at http://mammoth.bcm.tmc.edu/traceview/index.html. This webpage also links to sample trace results and a user manual that describes ET Viewer functions in detail.     

Structural and functional features of caudatocortical connections

Efferent connections of the caudate nucleus were studied experimentally in 13 cats after electrolytic destruction of various parts of it. Preparations were stained by the methods of Nauta, Knook, and Fink-Heimer. Direct caudatocortical connections with a definite topical organization were discovered: a ventrodorsal projection in the cortex corresponds to a rostrocaudal and ventrodorsal distribution of neurons in the caudate nucleus. Striatocortical fibers are few in number and very thin. Their predeterminals were found in both the deep and the superficial layers of the cortex on granule cells and pyramidal cells of different sizes. The results are in agreement with those of most of the recent physiological investigations indicating a close functional connection between the caudate nucleus and the cortex.     

Supraspinal connections of the reproductive organs: structural and functional aspects

Gonadal functions are governed by the hypothalamo-hypophyseal system. Other organs of the reproduction tract are under the regulatory action of gonadal steroids. In the past two decades several data have been accumulated on the involvement of fine-tuning control mechanisms which include autocrine and paracrine effects of biologically active substances produced locally and the regulatory action of nerves innervating the organs of the system. Recent studies using the viral transsynaptic technique have revealed cell groups in the central nervous system that are transneuronally connected with the male and female reproductive organs. This review summarizes neuromorphological data on the supraspinal innervation of reproductive organs and the functional significance of these brain areas in the control of reproduction.     

Wilder Penfield in the age of YouTube: visualizing the sequential activation of sensorimotor areas across neocortex

Flow of electrical activity across neocortex is essential for many sensorimotor tasks. Whether this flow is localized or spreads widely is unknown. Ferezou et al., imaging activity across the cortical mantle in awake mice, show in this issue of Neuron that touch by a single vibrissa leads to a rapid depolarization of primary sensory and motor areas that subsequently spreads across most of cortex.     

WebFEATURE: An interactive web tool for identifying and visualizing functional sites on macromolecular structures

WebFEATURE (http://feature.stanford.edu/webfeature/) is a web-accessible structural analysis tool that allows users to scan query structures for functional sites in both proteins and nucleic acids. WebFEATURE is the public interface to the scanning algorithm of the FEATURE package, a supervised learning algorithm for creating and identifying 3D, physicochemical motifs in molecular structures. Given an input structure or Protein Data Bank identifier (PDB ID), and a statistical model of a functional site, WebFEATURE will return rank-scored 'hits' in 3D space that identify regions in the structure where similar distributions of physicochemical properties occur relative to the site model. Users can visualize and interactively manipulate scored hits and the query structure in web browsers that support the Chime plug-in. Alternatively, results can be downloaded and visualized through other freely available molecular modeling tools, like RasMol, PyMOL and Chimera. A major application of WebFEATURE is in rapid annotation of function to structures in the context of structural genomics.     

GenomeViz: visualizing microbial genomes

Background

An increasing number of microbial genomes are being sequenced and deposited in public databases. In addition, several closely related strains are also being sequenced in order to understand the genetic basis of diversity and mechanisms that lead to the acquisition of new genetic traits. These exercises have necessitated the requirement for visualizing microbial genomes and performing genome comparisons on a finer scale. We have developed GenomeViz to enable rapid visualization and subsequent comparisons of several microbial genomes in an interactive environment.

Results

Here we describe a program that allows visualization of both qualitative and quantitative information from complete and partially sequenced microbial genomes. Using GenomeViz, data deriving from studies on genomic islands, gene/protein classifications, GC content, GC skew, whole genome alignments, microarrays and proteomics may be plotted. Several genomes can be visualized interactively at the same time from a comparative genomic perspective and publication quality circular genome plots can be created.

Conclusions

GenomeViz should allow researchers to perform visualization and comparative analysis of up to eight different microbial genomes simultaneously.

     

CNplot: visualizing pre-clustered networks

SUMMARY: CNplot is a simple technique for the visualization of global connectivity within pre-clustered network data. CNplot is easy to implement and in most cases produces informative and satisfactory summary of the data. AVAILABILITY: A Java implementation is available that allows users to modify graphics parameters and produces a LaTeX output. This software is free and is available at http://csb.stanford.edu/nbatada/VCN.html     

Animals,disease, and man: making connections

The intricate causal relationships between disease in man and disease in animals first began to be elucidated in the mid-19th century. Although the connections between animal and human disease are now generally understood, individuals as well as societies remain slow to act on this knowledge. This paper examines the gradual recognition of these disease connections and explores the parallel theme of man's reluctance to appreciate the implications of these connections. It identifies factors that have inhibited the realization of the links between disease in man and animals, and discusses several milestones in the scientific elucidation of these links. Beginning with emerging concerns over the relationship between bovine and human tuberculosis in the 1860s, it follows the discovery of insect vectors, animal reservoirs, and the links between animals, influenza, and man. Despite warnings of the potential significance for human disease of patterns of changes in the relationship with animals and the natural world, scientists have continued to treat human and animal health as largely independent disciplines, while historians too have neglected this important aspect of human disease.     

Nonparametric functional mapping of quantitative trait loci

Summary .  Functional mapping is a useful tool for mapping quantitative trait loci (QTL) that control dynamic traits. It incorporates mathematical aspects of biological processes into the mixture model-based likelihood setting for QTL mapping, thus increasing the power of QTL detection and the precision of parameter estimation. However, in many situations there is no obvious functional form and, in such cases, this strategy will not be optimal. Here we propose to use nonparametric function estimation, typically implemented with B-splines, to estimate the underlying functional form of phenotypic trajectories, and then construct a nonparametric test to find evidence of existing QTL. Using the representation of a nonparametric regression as a mixed model, the final test statistic is a likelihood ratio test. We consider two types of genetic maps: dense maps and general maps, and the power of nonparametric functional mapping is investigated through simulation studies and demonstrated by examples.     

np2QTL: networking phenotypic plasticity quantitative trait loci across heterogeneous environments

Despite its critical importance to our understanding of plant growth and adaptation, the question of how environment‐induced plastic response is affected genetically remains elusive. Previous studies have shown that the reaction norm of an organism across environmental index obeys the allometrical scaling law of part‐whole relationships. The implementation of this phenomenon into functional mapping can characterize how quantitative trait loci (QTLs) modulate the phenotypic plasticity of complex traits to heterogeneous environments. Here, we assemble functional mapping and allometry theory through Lokta?Volterra ordinary differential equations (LVODE) into an R‐based computing platform, np²QTL, aimed to map and visualize phenotypic plasticity QTLs. Based on LVODE parameters, np²QTL constructs a bidirectional, signed and weighted network of QTL?QTL epistasis, whose emergent properties reflect the ecological mechanisms for genotype?environment interactions over any range of environmental change. The utility of np²QTL was validated by comprehending the genetic architecture of phenotypic plasticity via the reanalysis of published plant height data involving 3502 recombinant inbred lines of maize planted in multiple discrete environments. np²QTL also provides a tool for constructing a predictive model of phenotypic responses in extreme environments relative to the median environment.     

A program to compare genetic differentiation statistics across loci using resampling of individuals and loci

Comparisons of genetic differentiation across populations based on different loci can provide insight into the evolutionary patterns acting on various regions of genomes. Here, we develop a program to statistically compare population genetic differentiation statistics (F(ST) or G'(ST) ) calculated from different loci. The program employs a routine that resamples either or both of individuals and loci and calculates a bootstrap confidence interval in the statistics. Resampling individuals is important when fewer than 25 individuals are sampled per population and when confidence intervals are required for individual loci. Resampling loci provides confidence intervals for sets of loci, such as a set presumed to be neutral, but can be anticonservative if fewer than 20 loci are analysed. We demonstrate the program using previously published data on the genetic differentiation at a major histocompatibility complex locus and at microsatellite loci across 10 populations of the guppy (Poecilia reticulata).     

Synaptic connections and functional organization in Aplysia buccal ganglia

The buccal ganglion of Aplysia contains three morpho-functional groups (A, B, and C) of large cells and two groups (s₁ and s₂) of small cells. The A cells evoke monosynaptic IPSPs in the B cells. We found that s₁ cells can evoke large EPSPs in the A cells, IEPSPs in the B cells, and EIIPSPs in the C cells; several s₁ cells are able to evoke all three types of responses. Many s₂ cells can evoke these same responses, but only in the A and B cells. Furthermore, the s cells can evoke depolarizing PSPs in other s cells; this relation is often reciprocal. All these responses may also be contralateral. Their monosynaptic nature is shown by the consistent 1:1 relationship with the presynaptic spike, and also by the effects of intracellular tetraethylammonium and of high Mg²⁺ concentration in the bathing medium. D-tubocurarine reversibly suppresses the I phase of the IEPSP evoked by the s cells in the B cells. All the responses evoked by the s cells undergo depression with repetition. The network formed by all these relations is outlined, and a double relationship proposed between s cells and B cells. By electrophysiological tracing of axonal pathways it is shown that the A cells send axons into the 3rd buccal nerve, the B cells into the 2nd and/or 3rd buccal nerve and in two cases into the redular nerve, and the C cells into the gastro-oesophageal nerve. Spontaneous synaptic activity of the buccal neurons appears to be formed mostly by the described PSPs. Spontaneous firing inside the isolated ganglion corresponds well to the alternate pattern of muscular contractions of the buccal mass.     

Electrophysiological analysis of the functional organization of cortico-cerebellar connections

The effect of stimulation of cortical association (orbito-frontal, parietal) and projection (auditory, sensomotor) areas on the activity of Purkinje neurons of the cerebellar cortex was studied in adult cats anesthetized with pentobarbital, with or without chloralose. These responses were compared with those to peripheral stimuli. Definite similarity was found between the responses of Purkinje cells to different cortical (association and projection) stimuli as regards both the types of responses of the neurons and their ability to respond. No similarity was observed in the responses of Purkinje cells to peripheral (visual, auditory, electrodermal) stimulation. Whereas almost identical numbers of neurons (over 50%) were excited in response to the different forms of cortical stimulation, the ability of the neurons to respond to peripheral stimuli differed considerably: 44.6% of neurons responded to electrodermal stimulation, 34.2% to auditory, and 18.8% to visual.Medical Institute, Kemerovo. Translated from Neirofiziologiya, Vol. 8, No. 5, pp. 483–489, September–October, 1976.