Super-paramagnetic clustering of yeast gene expression profiles

High-density DNA arrays, used to monitor gene expression at a genomic scale, have produced vast amounts of information which require the development of efficient computational methods to analyze them. The important first step is to extract the fundamental patterns of gene expression inherent in the data. This paper describes the application of a novel clustering algorithm, Super-Paramagnetic Clustering (SPC) to analysis of gene expression profiles that were generated recently during a study of the yeast cell cycle. SPC was used to organize genes into biologically relevant clusters that are suggestive for their co-regulation. Some of the advantages of SPC are its robustness against noise and initialization, a clear signature of cluster formation and splitting, and an unsupervised self-organized determination of the number of clusters at each resolution. Our analysis revealed interesting correlated behavior of several groups of genes which has not been previously identified

EvoluCode: Evolutionary Barcodes as a Unifying Framework for Multilevel Evolutionary Data

Evolutionary systems biology aims to uncover the general trends and principles governing the evolution of biological networks. An essential part of this process is the reconstruction and analysis of the evolutionary histories of these complex, dynamic networks. Unfortunately, the methodologies for representing and exploiting such complex evolutionary histories in large scale studies are currently limited. Here, we propose a new formalism, called EvoluCode (Evolutionary barCode), which allows the integration of different evolutionary parameters (eg, sequence conservation, orthology, synteny …) in a unifying format and facilitates the multilevel analysis and visualization of complex evolutionary histories at the genome scale. The advantages of the approach are demonstrated by constructing barcodes representing the evolution of the complete human proteome. Two large-scale studies are then described: (i) the mapping and visualization of the barcodes on the human chromosomes and (ii) automatic clustering of the barcodes to highlight protein subsets sharing similar evolutionary histories and their functional analysis. The methodologies developed here open the way to the efficient application of other data mining and knowledge extraction techniques in evolutionary systems biology studies. A database containing all EvoluCode data is available at: http://lbgi.igbmc.fr/barcodes

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Super paramagnetic clustering of DNA sequences

Master'sMASTER OF SCIENC

Simulations in statistical physics and biology: some applications

One of the most active areas of physics in the last decades has been that of critical phenomena, and Monte Carlo simulations have played an important role as a guide for the validation and prediction of system properties close to the critical points. The kind of phase transitions occurring for the Betts lattice (lattice constructed removing 1/7 of the sites from the triangular lattice) have been studied before with the Potts model for the values q=3, ferromagnetic and antiferromagnetic regime. Here, we add up to this research line the ferromagnetic case for q=4 and 5. In the first case, the critical exponents are estimated for the second order transition, whereas for the latter case the histogram method is applied for the occurring first order transition. Additionally, Domany's Monte Carlo based clustering technique mainly used to group genes similar in their expression levels is reviewed. Finally, a control theory tool --an adaptive observer-- is applied to estimate the exponent parameter involved in the well-known Gompertz curve. By treating all these subjects our aim is to stress the importance of cooperation between distinct disciplines in addressing the complex problems arising in biology. Contents: Chapter 1 - Monte Carlo simulations in stat. physics; Chapter 2: MC simulations in biology; Chapter 3: Gompertz equationComment: 82 pages, 33 figures, 4 tables, somewhat reduced version of the M.Sc. thesis defended in Jan. 2006 at IPICyT, San Luis Potosi, Mx. (Supervisers: Drs. R. Lopez-Sandoval and H.C. Rosu). Last sections 3.3 and 3.4 can be found at http://lanl.arxiv.org/abs/physics/041108

Structural Perspectives on Glycosaminoglycan-Binding Proteins and Their Receptors

abstract: Glycosaminoglycans (GAGs) are long chains of negatively charged sulfated polysaccharides. They are often found to be covalently attached to proteins and form proteoglycans in the extracellular matrix (ECM). Many proteins bind GAGs through electrostatic interactions. GAG-binding proteins (GBPs) are involved in diverse physiological activities ranging from bacterial infections to cell-cell/cell-ECM contacts. This thesis is devoted to understanding how interactions between GBPs and their receptors modulate biological phenomena. Bacteria express GBPs on surface that facilitate dissemination and colonization by attaching to host ECM. The first GBP investigated in this thesis is decorin binding protein (DBP) found on the surface of Borrelia burgdorferi, causative pathogens in Lyme disease. DBPs bind GAGs of decorin, a proteoglycan in ECM. Of the two isoforms, DBPB is less studied than DBPA. In current work, structure of DBPB from B. burgdorferi and its GAG interactions were investigated using solution NMR techniques. DBPB adopts a five-helical structure, similar to DBPA. Despite similar GAG affinities, DBPB has its primary GAG-binding site on the lysine-rich C terminus, which is different from DBPA. Besides GAGs, GBPs in ECM also interact with cell surface receptors, such as integrins. Integrins belong to a big family of heterodimeric transmembrane proteins that receive extracellular cues and transmit signals bidirectionally to regulate cell adhesion, migration, growth and survival. The second part of this thesis focuses on αM I-domain of the promiscuous integrin αMβ2 (Mac-1 or CD11b/CD18) and explores the structural mechanism of αM I-domain interactions with pleiotrophin (PTN) and platelet factor 4 (PF4), which are cationic proteins with high GAG affinities. After completing the backbone assignment of αM I-domain, paramagnetic relaxation enhancement (PRE) experiments were performed to show that both PTN and PF4 bind αM I-domain using metal ion dependent adhesion site (MIDAS) in an Mg2+ independent way, which differs from the classical Mg2+ dependent mechanism used by all known integrin ligands thus far. In addition, NMR relaxation dispersion analysis revealed unique inherent conformational dynamics in αM I-domain centered around MIDAS and the crucial C-terminal helix. These dynamic motions are potentially functionally relevant and may explain the ligand promiscuity of the receptor, but requires further studies.Dissertation/ThesisDoctoral Dissertation Biochemistry 201

clusterMaker: a multi-algorithm clustering plugin for Cytoscape

<p>Abstract</p> <p>Background</p> <p>In the post-genomic era, the rapid increase in high-throughput data calls for computational tools capable of integrating data of diverse types and facilitating recognition of biologically meaningful patterns within them. For example, protein-protein interaction data sets have been clustered to identify stable complexes, but scientists lack easily accessible tools to facilitate combined analyses of multiple data sets from different types of experiments. Here we present <it>clusterMaker</it>, a Cytoscape plugin that implements several clustering algorithms and provides network, dendrogram, and heat map views of the results. The Cytoscape network is linked to all of the other views, so that a selection in one is immediately reflected in the others. <it>clusterMaker </it>is the first Cytoscape plugin to implement such a wide variety of clustering algorithms and visualizations, including the only implementations of hierarchical clustering, dendrogram plus heat map visualization (tree view), k-means, k-medoid, SCPS, AutoSOME, and native (Java) MCL.</p> <p>Results</p> <p>Results are presented in the form of three scenarios of use: analysis of protein expression data using a recently published mouse interactome and a mouse microarray data set of nearly one hundred diverse cell/tissue types; the identification of protein complexes in the yeast <it>Saccharomyces cerevisiae</it>; and the cluster analysis of the vicinal oxygen chelate (VOC) enzyme superfamily. For scenario one, we explore functionally enriched mouse interactomes specific to particular cellular phenotypes and apply fuzzy clustering. For scenario two, we explore the prefoldin complex in detail using both physical and genetic interaction clusters. For scenario three, we explore the possible annotation of a protein as a methylmalonyl-CoA epimerase within the VOC superfamily. Cytoscape session files for all three scenarios are provided in the Additional Files section.</p> <p>Conclusions</p> <p>The Cytoscape plugin <it>clusterMaker </it>provides a number of clustering algorithms and visualizations that can be used independently or in combination for analysis and visualization of biological data sets, and for confirming or generating hypotheses about biological function. Several of these visualizations and algorithms are only available to Cytoscape users through the <it>clusterMaker </it>plugin. <it>clusterMaker </it>is available via the Cytoscape plugin manager.</p

SIMAP—structuring the network of protein similarities

Protein sequences are the most important source of evolutionary and functional information for new proteins. In order to facilitate the computationally intensive tasks of sequence analysis, the Similarity Matrix of Proteins (SIMAP) database aims to provide a comprehensive and up-to-date dataset of the pre-calculated sequence similarity matrix and sequence-based features like InterPro domains for all proteins contained in the major public sequence databases. As of September 2007, SIMAP covers ∼17 million proteins and more than 6 million non-redundant sequences and provides a complete annotation based on InterPro 16. Novel features of SIMAP include a new, portlet-based web portal providing multiple, structured views on retrieved proteins and integration of protein clusters and a unique search method for similar domain architectures. Access to SIMAP is freely provided for academic use through the web portal for individuals at http://mips.gsf.de/simap/and through Web Services for programmatic access at http://mips.gsf.de/webservices/services/SimapService2.0?wsdl