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by Sebastian Kühner, Vera van Noort, Matthew J. Betts, et al.Alejandra Leo-Macias, Claire Batisse, Michaela Rode, Takuji Yamada, Tobias Maier, Samuel Bader, Pedro Beltran-Alvarez, Daniel Castaño-Diez, Wei-Hua Chen, Damien Devos, Marc Güell, Tomas Norambuena, Ines Racke, Vladimir Rybin, Alexander Schmidt, Eva Yus, Ruedi Aebersold, Richard Herrmann, Bettina Böttcher, Achilleas S. Frangakis, Robert B. Russell, Luis Serrano, Peer Bork, Anne-Claude Gavin
Abstract
The genome of Mycoplasma pneumoniae is among the smallest found in self-replicating organisms. To study the basic principles of bacterial proteome organization, we used tandem affinity purification–mass spectrometry (TAP-MS) in a proteome-wide screen. The analysis revealed 62 homomultimeric and 116 heteromultimeric soluble protein complexes, of which the majority are novel. About a third of the heteromultimeric complexes show higher levels of proteome organization, including assembly into larger, multiprotein complex entities, suggesting sequential steps in biological processes, and extensive sharing of components, ...
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Abstract
A lack of information on protein-protein interactions at the host-pathogen interface is impeding the understanding of the pathogenesis process. A recently developed, homology search-based method to predict protein-protein interactions is applied to the gastric pathogen, Helicobacter pylori to predict the interactions between proteins of H. pylori and human proteins in vitro. Many of the predicted interactions could potentially occur between the pathogen and its human host during pathogenesis as we focused mainly on the H. pylori proteins that have a transmembrane ...
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Abstract
Systems biology offers the potential to provide new insights into our understanding of the pathogenesis of complex diseases such as atherosclerosis. It seeks to comprehend the system properties of the non-linear interactions of the multiple biomolecular components that characterize a living organism. An important component of this research approach is identifying the biological networks that connect the differing elements of a system and in the process describe the characteristics that define a shift in equilibrium from a healthy to a diseased ...
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Abstract
BACKGROUND:Gene promoters can be in various epigenetic states and undergo interactions with many molecules in a highly transient, probabilistic and combinatorial way, resulting in a complex global dynamics as observed experimentally. However, models of stochastic gene expression commonly consider promoter activity as a two-state on/off system. We consider here a model of single-gene stochastic expression that can represent arbitrary prokaryotic or eukaryotic promoters, based on the combinatorial interplay between molecules and epigenetic factors, including energy-dependent remodeling and enzymatic activities.RESULTS:We show that, ...
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by Timothy T. Perkins, Robert A. Kingsley, Maria C. Fookes, et al.Paul P. Gardner, Keith D. James, Lu Yu, Samuel A. Assefa, Miao He, Nicholas J. Croucher, Derek J. Pickard, Duncan J. Maskell, Julian Parkhill, Jyoti Choudhary, Nicholas R. Thomson, Gordon Dougan
Abstract
High-density, strand-specific cDNA sequencing (ssRNAâseq) was used to analyze the transcriptome of Salmonella enterica serovar Typhi (S. Typhi). By mapping sequence data to the entire S. Typhi genome, we analyzed the transcriptome in a strand-specific manner and further defined transcribed regions encoded within prophages, pseudogenes, previously un-annotated, and 3â²- or 5â²-untranslated regions (UTR). An additional 40 novel candidate non-coding RNAs were identified beyond those previously annotated. Proteomic analysis was combined with transcriptome data to confirm and refine the annotation of a ...
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Abstract
Cellular networks display modular organization at different levels, from small sets of genes exchanging signals in morphogenesis to large groups of proteins involved in cell death. At the smallest scale, minute groups of interacting proteins or genes, so-called ‘network motifs’, have been suggested to be the functional building blocks of network biology. In this context, the relative abundance of a network motif would reflect its adaptive value. However, although the overabundance of motifs is non-random, recent studies by Mazurie et al. ...
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Current topics in microbiology and immunology, Vol. 306 (2006), pp. 153-182
Abstract
The airway provides numerous defense mechanisms to prevent microbial colonization by the large numbers of bacteria and viruses present in ambient air. An important component of this defense is the antimicrobial peptides and proteins present in the airway surface fluid (ASF), the mucin-rich fluid covering the respiratory epithelium. These include larger proteins such as lysozyme and lactoferrin, as well as the cationic defensin and cathelicidin peptides. While some of these peptides, such as human beta-defensin (hBD)-1, are present constitutively, others, including ...
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Abstract
Despite remarkable advances in diagnosis and therapy, ischemic heart disease (IHD) remains a leading cause of morbidity and mortality in industrialized countries. Recent efforts to estimate the influence of genetic variation on IHD risk have focused on predicting individual plasma high-density lipoprotein cholesterol (HDL-C) concentration. Plasma HDL-C concentration (mg/dl), a quantitative risk factor for IHD, has a complex multifactorial etiology that involves the actions of many genes. Single gene variations may be necessary but are not individually sufficient to predict a ...
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by L. M. Stuart, J. Boulais, G. M. Charriere, et al.E. J. Hennessy, S. Brunet, I. Jutras, G. Goyette, C. Rondeau, S. Letarte, H. Huang, P. Ye, F. Morales, C. Kocks, J. S. Bader, M. Desjardins, R. A. Ezekowitz
Abstract
Phagocytes have a critical function in remodelling tissues during embryogenesis and thereafter are central effectors of immune defence. During phagocytosis, particles are internalized into 'phagosomes', organelles from which immune processes such as microbial destruction and antigen presentation are initiated. Certain pathogens have evolved mechanisms to evade the immune system and persist undetected within phagocytes, and it is therefore evident that a detailed knowledge of this process is essential to an understanding of many aspects of innate and adaptive immunity. However, despite ...
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Abstract
Our views of both innate and adaptive immunity have been significantly modified by recent studies of immune receptors and immunity in protostomes, invertebrate deuterostomes, and jawless vertebrates. Extraordinary variation in the means whereby organisms recognize pathogens has been revealed by a series of recent findings, including: novel forms of familiar immune receptors, high genetic polymorphism for new receptor types, germline rearrangement for non-Ig domain receptors, somatic variation of germline-encoded receptors, and unusually complex alternative splicing of genes with both immune ...
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Biochemistry and Molecular Biology Education, Vol. 37, No. 6. (1 November 2009), pp. 377-377, doi:10.1002/bmb.20340
Abstract
No abstract. ...
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Abstract
BACKGROUND:When processing microarray data sets, we recently noticed that some gene names were being changed inadvertently to non-gene names.RESULTS:A little detective work traced the problem to default date format conversions and floating-point format conversions in the very useful Excel program package. The date conversions affect at least 30 gene names; the floating-point conversions affect at least 2,000 if Riken identifiers are included. These conversions are irreversible; the original gene names cannot be recovered.CONCLUSIONS:Users of Excel for analyses involving gene names should ...
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Trends in biochemical sciences, Vol. 29, No. 3. (March 2004), pp. 106-110
posted to blog_scientific_tools
by freesci
on 2009-12-14 14:12:19
Abstract
We have identified a new domain in a broad range of bacterial, as well as single archaeal and plant proteins. Its presence in the virulence-related pXO1 plasmid of Bacillus anthracis as well as in several other pathogens makes it a possible drug target. We term the new domain nuclease-related domain (NERD) because of its distant similarity to endonucleases. ...
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Abstract
BACKGROUND: ESTs or variable sequence reads can be available in prokaryotic studies well before a complete genome is known. Use cases include (i) transcriptome studies or (ii) single cell sequencing of bacteria. Without suitable software their further analysis and mapping would have to await finalization of the corresponding genome. RESULTS: The tool JANE rapidly maps ESTs or variable sequence reads in prokaryotic sequencing and transcriptome efforts to related template genomes. It provides an easy-to-use graphics interface for information retrieval and a ...
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Abstract
Summary: With an exponentially growing number of articles being published every year, scientists can use some help in determining which journal is most appropriate for publishing their results, and which other scientists can be called upon to review their work. ...
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In The Fourth Paradigm: Data-Intensive Scientific Discovery (2009)
Abstract
A collection of essays expanding on the vision of pioneering computer scientist Jim Gray for a new, fourth paradigm of discovery based on data-intensive science. ...
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Abstract
Due to the rapid release of new data from genome sequencing projects, the majority of protein sequences in public databases have not been experimentally characterized; rather, sequences are annotated using computational analysis. The level of misannotation and the types of misannotation in large public databases are currently unknown and have not been analyzed in depth. We have investigated the misannotation levels for molecular function in ...
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Abstract
BACKGROUND:The availability of hundreds of bacterial genomes allowed a comparative genomic study of the Type VI Secretion System (T6SS), recently discovered as being involved in pathogenesis. By combining comparative and phylogenetic approaches using more than 500 prokaryotic genomes, we characterized the global T6SS genetic structure in terms of conservation, evolution and genomic organization.RESULTS:This genome wide analysis allowed the identification of a set of 13 proteins constituting the T6SS protein core and a set of conserved accessory proteins. 176 T6SS loci (encompassing ...
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Abstract
Much attention has recently been given to the statistical significance of topological features observed in biological networks. Here, we consider residue interaction graphs (RIGs) as network representations of protein structures with residues as nodes and inter-residue interactions as edges. Degree-preserving randomized models have been widely used for this purpose in biomolecular networks. However, such a single summary statistic of a network may not be detailed enough to capture the complex topological characteristics of protein structures and their network counterparts. Here, we ...
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Abstract
Individuals' use of language in contexts emerges from second-to-second processes of activating and integrating traces of past experiences2014an interactionist view compatible with the study of language as a complex adaptive system but quite different from the trait-based framework through which measurement specialists investigate validity, establish reliability, and ensure fairness of assessments. This article discusses assessment arguments from an interactionist perspective. We argue that the familiar concepts and methods of assessment that evolved under a trait perspective can be gainfully reconceived in ...
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by The “Five Graces Group”, Clay Beckner, Richard Blythe, et al.Joan Bybee, Morten H. Christiansen, William Croft, Nick C. Ellis, John Holland, Jinyun Ke, Diane Larsen-Freeman, Tom Schoenemann
Abstract
Language has a fundamentally social function. Processes of human interaction along with domain-general cognitive processes shape the structure and knowledge of language. Recent research in the cognitive sciences has demonstrated that patterns of use strongly affect how language is acquired, is used, and changes. These processes are not independent of one another but are facets of the same complex adaptive system (CAS). Language as a CAS involves the following key features: The system consists of multiple agents (the speakers in the speech community) ...
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by Ying Zhang, Ines Thiele, Dana Weekes, et al.Zhanwen Li, Lukasz Jaroszewski, Krzysztof Ginalski, Ashley M. Deacon, John Wooley, Scott A. Lesley, Ian A. Wilson, Bernhard Palsson, Andrei Osterman, Adam Godzik
Abstract
Metabolic pathways have traditionally been described in terms of biochemical reactions and metabolites. With the use of structural genomics and systems biology, we generated a three-dimensional reconstruction of the central metabolic network of the bacterium Thermotoga maritima. The network encompassed 478 proteins, of which 120 were determined by experiment and 358 were modeled. Structural analysis revealed that proteins forming the network are dominated by a small number (only 182) of basic shapes (folds) performing diverse but mostly related functions. Most of ...
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Abstract
Based on several protein-protein interaction (PPI) networks obtained from the Database of Interacting Proteins (DIP) and other public databases, we demonstrate that our method is able to detect biologically significant pathways that are conserved across different organisms. Our algorithm has a polynomial complexity that grows linearly with the size of the aligned paths. This enables the search for very long paths with more than 10 nodes within a few minutes on a desktop computer. The software program that implements this algorithm ...
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Abstract
There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there ...
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Abstract
In this article I propose the classification of the evolutionary stages that a scientific discipline evolves through and the type of scientists that are the most productive at each stage. I believe that each scientific discipline evolves sequentially through four stages. Scientists at stage one introduce new objects and phenomena as subject matter for a new scientific discipline. To do this they have to introduce ...
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Proceedings of the National Academy of Sciences of the United States of America, Vol. 101 Suppl 1, No. Suppl 1. (6 April 2004), pp. 5266-5273, doi:10.1073/pnas.0307625100
Abstract
There has been a long history of research into the structure and evolution of mankind's scientific endeavor. However, recent progress in applying the tools of science to understand science itself has been unprecedented because only recently has there been access to high-volume and high-quality data sets of scientific output (e.g., publications, patents, grants) and computers and algorithms capable of handling this enormous stream of data. ...
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Abstract
10.1126/science.1184202 ...
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Abstract
The authors discuss the value of article-level metrics in determining an article's scientific impact. ...
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by Marc Güell, Vera van Noort, Eva Yus, et al.Wei-Hua Chen, Justine Leigh-Bell, Konstantinos Michalodimitrakis, Takuji Yamada, Manimozhiyan Arumugam, Tobias Doerks, Sebastian Kühner, Michaela Rode, Mikita Suyama, Sabine Schmidt, Anne-Claude Gavin, Peer Bork, Luis Serrano
Abstract
To study basic principles of transcriptome organization in bacteria, we analyzed one of the smallest self-replicating organisms, Mycoplasma pneumoniae. We combined strand-specific tiling arrays, complemented by transcriptome sequencing, with more than 252 spotted arrays. We detected 117 previously undescribed, mostly noncoding transcripts, 89 of them in antisense configuration to known genes. We identified 341 operons, of which 139 are polycistronic; almost half of the latter show decaying expression in a staircase-like manner. Under various conditions, operons could be divided into 447 ...
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Acta biochimica Polonica, Vol. 52, No. 1. (2005), pp. 267-269
Abstract
MOFOID is a new server developed mainly for automated modeling of protein structures by their homology to the structures deposited in the PDB database. Selection of a template and calculation of the alignment is performed with the Smith-Waterman or Needleman-Wunsch algorithms implemented in the EMBOSS package. The final model is built and optimised with programs from the JACKAL package. The wide spectrum of options in the web-based interface and the possibility of uploading user's own alignment make MOFOID a suitable platform ...
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Abstract
Non-fimbrial adhesins, such as Yersinia YadA, Moraxella UspA1 and A2, Haemophilus Hia and Hsf, or Bartonella BadA represent an important class of molecules by which pathogenic proteobacteria adhere to their hosts. They form trimeric surface structures with a head–stalk–anchor architecture. Whereas head and stalk domains are diverse and appear (frequently repetitively) in different combinations, the anchor domains are homologous and display the properties of autotransporters. We have built a molecular model for the prototypical non-fimbrial adhesin, YadA, by combining the crystal ...
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Abstract
The Yersinia adhesin A (YadA) is a trimeric autotransporter adhesin of enteric yersiniae. It consists of three major domains: a head mediating adherence to host cells, a stalk involved in serum resistance, and an anchor that forms a membrane pore and is responsible for the autotransport function. The anchor contains a glycine residue, nearly invariant throughout trimeric autotransporter adhesins, that faces the pore lumen. To address the role of this glycine, we replaced it with polar amino acids of increasing side ...
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Abstract
MOTIVATION: Trimeric autotransporter adhesins (TAAs), such as Yersinia YadA, Neisseria NadA, Moraxella UspAs, Haemophilus Hia and Bartonella BadA, are important pathogenicity factors of proteobacteria. Their high sequence diversity and distinct mosaic-like structure lead to difficulties in the annotation of their sequences. These stem from the large number of short repeats, the presence of compositionally unusual coiled-coils, fuzzy domain boundaries and regions of seemingly low sequence complexity. RESULTS: We have developed a workflow, named daTAA, for the accurate domain annotation of TAAs. ...
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Abstract
Trimeric autotransporter adhesins (TAAs) are a major class of proteins by which pathogenic proteobacteria adhere to their hosts. Prominent examples include Yersinia YadA, Haemophilus Hia and Hsf, Moraxella UspA1 and A2, and Neisseria NadA. TAAs also occur in symbiotic and environmental species and presumably represent a general solution to the problem of adhesion in proteobacteria. The general structure of TAAs follows a head-stalk-anchor architecture, where the heads are the primary mediators of attachment and autoagglutination. In the major adhesin of Bartonella ...
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Abstract
PorT is a membrane-associated protein shown to be essential for the maturation and secretion of a class of cysteine proteinases, the gingipains, from the periodontal pathogen Porphyromonas gingivalis. It was previously reported that PorT is located on the periplasmic surface of the inner membrane to function as a chaperone for the maturing proteinases. Our modelling suggested it to be an integral outer-membrane protein with eight anti-parallel, membrane-traversing beta-strands. In this report, the outer-membrane localization model was confirmed by the structural and ...
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(22 Sep 2009)
Abstract
The use of networks to integrate different genetic, proteomic, and metabolic datasets has been proposed as a viable path toward elucidating the origins of specific diseases. Here we introduce a new phenotypic database summarizing correlations obtained from the disease history of more than 30 million patients in a Phenotypic Disease Network (PDN). We present evidence that the structure of the PDN is relevant to the understanding of illness progression by showing that (1) patients develop diseases close in the network to those they already have; (2) the progression ...
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(24 Mar 2006)
Abstract
In this chapter, I review the main methods and techniques of complex systems science. As a first step, I distinguish among the broad patterns which recur across complex systems, the topics complex systems science commonly studies, the tools employed, and the foundational science of complex systems. The focus of this chapter is overwhelmingly on the third heading, that of tools. These in turn divide, roughly, into tools for analyzing data, tools for constructing and evaluating models, and tools for measuring complexity. I discuss the principles of statistical learning ...
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(6 Sep 2006)
Abstract
Since its application to systems, emergence has been explained in terms of levels of observation. This approach has led to confusion, contradiction, incoherence and at times mysticism. When the idea of level is replaced by a framework of scope, resolution and state, this confusion is dissolved. We find that emergent properties are determined by the relationship between the scope of macrostate and microstate descriptions. This establishes a normative definition of emergent properties and emergence that makes sense of previous descriptive definitions of emergence. In particular, this framework sheds ...
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Abstract
The bacterial cell-envelope consists of a complex arrangement of lipids, proteins and carbohydrates that serves as the interface between a microorganism and its environment or, with pathogens, a human host. Escherichia coli has long been investigated as a leading model system to elucidate the fundamental mechanisms underlying microbial cell-envelope biology. This includes extensive descriptions of the molecular identities, biochemical activities and evolutionary trajectories of integral transmembrane proteins, many of which play critical roles in infectious disease and antibiotic resistance. Strikingly, however, ...
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Nucleic Acids Research In Nucl. Acids Res., Vol. 38, No. suppl 1. (01 January 2010), pp. D540-D544, doi:10.1093/nar/gkp1026
by Pawel Smialowski, Philipp Pagel, Philip Wong, et al.Barbara Brauner, Irmtraud Dunger, Gisela Fobo, Goar Frishman, Corinna Montrone, Thomas Rattei, Dmitrij Frishman, Andreas Ruepp
Abstract
The Negatome is a collection of protein and domain pairs that are unlikely to be engaged in direct physical interactions. The database currently contains experimentally supported non-interacting protein pairs derived from two distinct sources: by manual curation of literature and by analyzing protein complexes with known 3D structure. More stringent lists of non-interacting pairs were derived from these two datasets by excluding interactions detected by high-throughput approaches. Additionally, non-interacting protein domains have been derived from the stringent manual and structural data, ...
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Abstract
Many networks in nature, society and technology are characterized by a mesoscopic level of organization, with groups of nodes forming tightly connected units, called communities or modules, that are only weakly linked to each other. Uncovering this community structure is one of the most important problems in the field of complex networks. Networks often show a hierarchical organization, with communities embedded within other communities; moreover, nodes can be shared between different communities. Here, we present the first algorithm that finds both ...
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Abstract
A conceptual framework for integrating diverse functional genomics data was developed by reinterpreting experiments to provide numerical likelihoods that genes are functionally linked. This allows direct comparison and integration of different classes of data. The resulting probabilistic gene network estimates the functional coupling between genes. Within this framework, we reconstructed an extensive, high-quality functional gene network for Saccharomyces cerevisiae, consisting of 4681 (∼81%) of the known yeast genes linked by ∼34,000 probabilistic linkages comparable in accuracy to small-scale interaction assays. The ...
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Abstract
Recent studies of cellular networks have revealed modular organizations of genes and proteins. For example, in interactome networks, a module refers to a group of interacting proteins that form molecular complexes and/or biochemical pathways and together mediate a biological process. However, it is still poorly understood how biological information is transmitted between different modules. We have developed information flow analysis, a new computational approach that identifies proteins central to the transmission of biological information throughout the network. In the information flow ...
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Abstract
AbstractObjective To understand belief in a specific scientific claim by studying the pattern of citations among papers stating it.Design A complete citation network was constructed from all PubMed indexed English literature papers addressing the belief that β amyloid, a protein accumulated in the brain in Alzheimer’s disease, is produced by and injures skeletal muscle of patients with inclusion body myositis. Social network theory and graph theory were used to analyse this network.Main outcome measures Citation bias, amplification, and invention, and their ...
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