Self-organizing maps: stationary states,metastability and convergence rate

We investigate the effect of various types of neighborhood function on the convergence rates and the presence or absence of metastable stationary states of Kohonen's self-organizing feature map algorithm in one dimension. We demonstrate that the time necessary to form a topographic representation of the unit interval [0, 1] may vary over several orders of magnitude depending on the range and also the shape of the neighborhood function, by which the weight changes of the neurons in the neighborhood of the winning neuron are scaled. We will prove that for neighborhood functions which are convex on an interval given by the length of the Kohonen chain there exist no metastable states. For all other neighborhood functions, metastable states are present and may trap the algorithm during the learning process. For the widely-used Gaussian function there exists a threshold for the width above which metastable states cannot exist. Due to the presence or absence of metastable states, convergence time is very sensitive to slight changes in the shape of the neighborhood function. Fastest convergence is achieved using neighborhood functions which are "convex" over a large range around the winner neuron and yet have large differences in value at neighboring neurons.     

Self-organizing maps and molecular similarity

Self-organizing maps generated by Kohonen neural networks provide a method for transforming multidimensional problems into lower dimensional problems. Here, a Kohonen network is used to generate two-dimensional representations of the electrostatic potential about the ring structures of histamine H2 agonists. Previous work by J. Gasteiger and X. Li (Angew. Chem. Int. Ed. Engl. 1994, 33, 643) has shown the usefulness of such a method for classifying molecules as muscarinic or nicotinic agonists. Here, the method is extended to rank histamine H2 agonists in order of biological activity.     

ALLMAPS: robust scaffold ordering based on multiple maps

The ordering and orientation of genomic scaffolds to reconstruct chromosomes is an essential step during de novo genome assembly. Because this process utilizes various mapping techniques that each provides an independent line of evidence, a combination of multiple maps can improve the accuracy of the resulting chromosomal assemblies. We present ALLMAPS, a method capable of computing a scaffold ordering that maximizes colinearity across a collection of maps. ALLMAPS is robust against common mapping errors, and generates sequences that are maximally concordant with the input maps. ALLMAPS is a useful tool in building high-quality genome assemblies. ALLMAPS is available at: https://github.com/tanghaibao/jcvi/wiki/ALLMAPS.     

An analysis of Kohonen's self-organizing maps using a system of energy functions

In this paper a new method for analyzing Kohonen's self-organizing feature maps is presented. The method makes use of a system of energy functions, one energy function for each processing unit. It is shown that the training process is equivalent to minimizing each energy function subject to constraints. The analysis is used to prove the formation of topologically correct maps when the inherent dimensionality of the input patterns matches that of the network. The energy equations can be used to compute the steady-state weight values of the network. In addition, the analysis allows bounds on the training parameters to be determined. Finally, examples of energy landscapes are presented to graphically show the behavior of the network.     

Ankyrin: structure, properties, and functions

Recent data on characteristics of the structure, functions, and main properties of ankyrins (proteins that are linkers between the spectrin-based cytoskeleton and integral membrane proteins) are summarized. The interactions of ankyrins with band-3 protein, P-type ATPases, ion channels, receptors, and protein kinase C are considered. The structure of ankyrin repeats that are often contained in other proteins (which are not classified with the ankyrin family) and ensure protein-protein interactions as well as interactions between proteins and nucleic acids is described in details. The mechanisms of regulation of the ability of ankyrins to interact with other proteins (alternative splicing and post-translational modification, including phosphorylation) are also considered.     

Protein--protein interaction maps: a lead towards cellular functions

The availability of complete genome sequences now permits the development of tools for functional biology on a proteomic scale. Several experimental approaches or in silico algorithms aim at clustering proteins into networks with biological significance. Among those, the yeast two-hybrid system is the technology of choice to detect protein-protein interactions. Recently, optimized versions were applied at a genomic scale, leading to databases on the web. However, as with any other 'genetic' assay, yeast two-hybrid assays are prone to false positives and false negatives. Here we discuss these various technologies, their general limitations and the potential advances they make possible, especially when in combination with other functional genomics or bioinformatics analyses.     

Isozymes of plant hexokinase: occurrence, properties and functions

Hexokinase (HK) occurs in all phyla, as an enzyme of the glycolytic pathway. Its importance in plant metabolism has emerged with compelling evidence that its preferential substrate, glucose, is both a nutrient and a signal molecule that controls development and expression of different classes of genes. A variety of plant tissues and organs have been shown to express multiple HK isoforms with different kinetic properties and subcellular localizations. Although plant HK is known to fulfill a catalytic function and act as a glucose sensor, the physiological relevance of plural isoforms and their contribution to either function are still poorly understood. We review here the current knowledge and hypotheses on the physiological roles of plant HK isoforms that have been identified and characterized. Recent findings provide hints on how the expression patterns, biochemical properties and subcellular localizations of HK isoforms may relate to their modes of action. Special attention is devoted to kinetic, mutant and transgenic data on HKs from Arabidopsis thaliana and the Solanaceae potato, tobacco, and tomato, as well as HK gene expression data from Arabidopsis public DNA microarray resources. Similarities and differences to known properties of animal and yeast HKs are also discussed as they may help to gain further insight into the functional adaptations of plant HKs.     

Metabolic maps and functions of the Plasmodium mitochondrion

The mitochondrion of Plasmodium species is a validated drug target. However, very little is known about the functions of this organelle. In this review, we utilize data available from the Plasmodium falciparum genome sequencing project to piece together putative metabolic pathways that occur in the parasite, comparing this with the existing biochemical and cell biological knowledge. The Plasmodium mitochondrion contains both conserved and unusual features, including an active electron transport chain and many of the necessary enzymes for coenzyme Q and iron-sulphur cluster biosynthesis. It also plays an important role in pyrimidine metabolism. The mitochondrion participates in an unusual hybrid haem biosynthesis pathway, with enzymes localizing in both the mitochondrion and plastid organelles. The function of the tricarboxylic acid cycle in the mitochondrion is unclear. We discuss directions for future research into this fascinating, yet enigmatic, organelle.     

Mammalian metallothioneins: properties and functions

Metallothioneins (MT) are a family of ubiquitous proteins, whose role is still discussed in numerous papers, but their affinity to some metal ions is undisputable. These cysteine-rich proteins are connected with antioxidant activity and protective effects on biomolecules against free radicals, especially reactive oxygen species. In this review, the connection between zinc(II) ions, reactive oxygen species, heavy metal ions and metallothioneins is demonstrated with respect to effect of these proteins on cell proliferation and a possible negative role in resistance to heavy metal-based and non-heavy metal-based drugs.     

Convergence properties of Kohonen's topology conserving maps: fluctuations,stability, and dimension selection

We analyse a Markovian algorithm for the formation of topologically correct feature maps proposed earlier by Kohonen. The maps from a space of input signals onto an array of formal neurons are generated by a learning scheme driven by a random sequence of input samples. The learning is described by an equivalent Fokker-Planck equation. Convergence to an equilibrium map can be ensured by a criterion for the time dependence of the learning step size. We investigate the stability of the equilibrium map and calculate the fluctuations around it. We also study an instability responsible for a phenomenon termed by Kohonen automatic selection of feature dimensions.     

Self-organizing maps: A tool to ascertain taxonomic relatedness based on features derived from 16S rDNA sequence

Exploitation of microbial wealth, of which almost 95% or more is still unexplored, is a growing need. The taxonomic placements of a new isolate based on phenotypic characteristics are now being supported by information preserved in the 16S rRNA gene. However, the analysis of 16S rDNA sequences retrieved from metagenome, by the available bioinformatics tools, is subject to limitations. In this study, the occurrences of nucleotide features in 16S rDNA sequences have been used to ascertain the taxonomic placement of organisms. The tetra- and penta-nucleotide features were extracted from the training data set of the 16S rDNA sequence, and was subjected to an artificial neural network (ANN) based tool known as self-organizing map (SOM), which helped in visualization of unsupervised classification. For selection of significant features, principal component analysis (PCA) or curvilinear component analysis (CCA) was applied. The SOM along with these techniques could discriminate the sample sequences with more than 90% accuracy, highlighting the relevance of features. To ascertain the confidence level in the developed classification approach, the test data set was specifically evaluated for Thiobacillus, with Acidiphilium, Paracocus and Starkeya, which are taxonomically reassigned. The evaluation proved the excellent generalization capability of the developed tool. The topology of genera in SOM supported the conventional chemo-biochemical classification reported in the Bergey manual.     

Hypothalamic control of energy balance: different peptides, different functions

Energy balance is maintained via a homeostatic system involving both the brain and the periphery. A key component of this system is the hypothalamus. Over the past two decades, major advances have been made in identifying an increasing number of peptides within the hypothalamus that contribute to the process of energy homeostasis. Under stable conditions, equilibrium exists between anabolic peptides that stimulate feeding behavior, as well as decrease energy expenditure and lipid utilization in favor of fat storage, and catabolic peptides that attenuate food intake, while stimulating sympathetic nervous system (SNS) activity and restricting fat deposition by increasing lipid metabolism. The equilibrium between these neuropeptides is dynamic in nature. It shifts across the day-night cycle and from day to day and also in response to dietary challenges as well as peripheral energy stores. These shifts occur in close relation to circulating levels of the hormones, leptin, insulin, ghrelin and corticosterone, and also the nutrients, glucose and lipids. These circulating factors together with neural processes are primary signals relaying information regarding the availability of fuels needed for current cellular demand, in addition to the level of stored fuels needed for long-term use. Together, these signals have profound impact on the expression and production of neuropeptides that, in turn, initiate the appropriate anabolic or catabolic responses for restoring equilibrium. In this review, we summarize the evidence obtained on nine peptides in the hypothalamus that have emerged as key players in this process. Data from behavioral, physiological, pharmacological and genetic studies are described and consolidated in an attempt to formulate a clear statement on the underlying function of each of these peptides and also on how they work together to create and maintain energy homeostasis.     

Experimental conformational energy maps of proteins and peptides

We have presented an extensive analysis of the peptide backbone dihedral angles in the PDB structures and computed experimental Ramachandran plots for their distributions seen under a various constraints on X‐ray resolution, representativeness at different sequence identity percentages, and hydrogen bonding distances. These experimental distributions have been converted into isoenergy contour plots using the approach employed previously by F. M. Pohl. This has led to the identification of energetically favored minima in the Ramachandran (? , ψ ) plots in which global minima are predominantly observed either in the right‐handed α‐helical or the polyproline II regions. Further, we have identified low energy pathways for transitions between various minima in the (? ,ψ ) plots. We have compared and presented the experimental plots with published theoretical plots obtained from both molecular mechanics and quantum mechanical approaches. In addition, we have developed and employed a root mean square deviation (RMSD) metric for isoenergy contours in various ranges, as a measure (in kcal.mol^?1) to compare any two plots and determine the extent of correlation and similarity between their isoenergy contours. In general, we observe a greater degree of compatibility with experimental plots for energy maps obtained from molecular mechanics methods compared to most quantum mechanical methods. The experimental energy plots we have investigated could be helpful in refining protein structures obtained from X‐ray, NMR, and electron microscopy and in refining force field parameters to enable simulations of peptide and protein structures that have higher degree of consistency with experiments. Proteins 2017; 85:979–1001. © 2017 Wiley Periodicals, Inc.     

l-Amino acid oxidases from microbial sources: types,properties, functions,and applications

l-Amino acid oxidases (LAAOs), which catalyze the stereospecific oxidative deamination of l-amino acids to α-keto acids and ammonia, are flavin adenine dinucleotide-containing homodimeric proteins. l-Amino acid oxidases are widely distributed in diverse organisms and have a range of properties. Because expressing LAAOs as recombinant proteins in heterologous hosts is difficult, their biotechnological applications have not been thoroughly advanced. LAAOs are thought to contribute to amino acid catabolism, enhance iron acquisition, display antimicrobial activity, and catalyze keto acid production, among other roles. Here, we review the types, properties, structures, biological functions, heterologous expression, and applications of LAAOs obtained from microbial sources. We expect this review to increase interest in LAAO studies.     

Myosin VI: cellular functions and motor properties

Myosin VI has been localized in membrane ruffles at the leading edge of cells, at the trans-Golgi network compartment of the Golgi complex and in clathrin-coated pits or vesicles, indicating that it functions in a wide variety of intracellular processes. Myosin VI moves along actin filaments towards their minus end, which is the opposite direction to all of the other myosins so far studied (to our knowledge), and is therefore thought to have unique properties and functions. To investigate the cellular roles of myosin VI, we identified various myosin VI binding partners and are currently characterizing their interactions within the cell. As an alternative approach, we have expressed and purified full-length myosin VI and studied its in vitro properties. Previous studies assumed that myosin VI was a dimer, but our biochemical, biophysical and electron microscopic studies reveal that myosin VI can exist as a stable monomer. We observed, using an optical tweezers force transducer, that monomeric myosin VI is a non-processive motor which, despite a relatively short lever arm, generates a large working stroke of 18 nm. Whether monomer and/or dimer forms of myosin VI exist in cells and their possible functions will be discussed.